Journal articles on the topic '(477.43)"19" (043.3/.5)'

ObjectivesThis is the first Europe-wide study aiming to describe the medication use in Neonatal Intensive Care Units and to analyse the factors that might influence the prescription pattern.MethodsA pan-European one day point-prevalence study was conducted in 2012 where all of the prescriptions for hospitalised neonates were recorded. A trade name, manufacturer, active pharmaceutical ingredients (API), strength, galenic form and route of administration were registered.ResultsAltogether 2173 prescriptions were administered to 726 neonates from 21 countries, of whom 66% (477/726) were preterm, 12% (84/726) extremely preterm. There was inverse correlation between gestational age (GA) and median number of prescriptions per neonate (group median 2/IQR 1–4, extremely preterm 4/3–6, very preterm 3/2–5, late preterm 2/1–3, full-term 2/1–3). Median number of prescriptions per neonate was highest in the eastern region, among extremely preterm neonates (median=6.5/IQR 6–8.5). Highest prescription rate was for alimentary medicines (93/per 100 admissions), systemic antiinfectives (79/100) and medicines for blood (71/100). Antiinfectives were most frequently prescribed in the southern region (103/100). Multivitamins were most frequently used medications in most regions (western 74, southern 31, northern 31/100), except in eastern region (5/100). Most commonly prescribed API-s were multivitamins (32/100), caffeine (19/100), gentamicin (18/100), amino acids (18/100) and colecalciferol (15/100). Most frequently prescribed medications among extremely preterm neonates were caffeine (60/100), among very preterms multivitamins and caffeine (45 and 43/100), among late preterms multivitamins (44/100) and among full-terms phytomenadione (26/100) and gentamicin (24/100).ConclusionsOur study revealed the most commonly used medications in neonates. Higher prescription rate among preterm neonates calls for further analysis of the suitability and safety of medications for infants with lower GA.

TPS600 Background: This phase III post-NC trial evaluates if CWRNRT post-Mx or whole breast irradiation (WBI) with RNRT after BCS significantly reduces the IBCR-FI rate in pts with PPAx nodes that are pathologically negative after NC. Secondary aims are OS, LRR-FI, DR-FI, DFS-DCIS, second primary cancer, and comparison of RT effect on cosmesis in reconstructed Mx pts. Correlative science examines RT effect by tumor subtype, molecular outcome predictors for residual disease, and predictors for the degree of reduction in loco-regional recurrence. Methods: Clinical T1-3, N1 IBC PPAx nodes (FNA or core needle biopsy) pts complete ≥8 weeks of NC (anthracycline and/or taxane). HER2+ pts receive anti-HER2 therapy. Following NC, BCS or Mx, sentinel node biopsy (≥2 nodes) and/or Ax dissection with histologically negative nodes is performed. ER/PR and HER-2neu status before NC is required. Pts may receive appropriate adjuvant systemic therapy. Radiation credentialing with a facility questionnaire/case benchmark is required. Random assignment for Mx pts is to no CWRNRT or CWRNRT and for BCS pts to WBI or WBI+RNRT. Statistics: 1,636 pts are to be enrolled over 5 yrs (definitive analysis at 7.5 yrs). Study is powered at 80% to test that RT reduces the annual hazard rate of events for IBCR-FI by 35% for an absolute risk reduction of 4.6% (5-yr cumulative rate). Intent-to-treat analysis with 3 interim analyses (43, 86, and 129 events) and a 4th/final analysis at 172 events. Pt-reported outcomes focusing on RT effect will be provided by 736 pts before random assignment and at 3, 6, 12, and 24 mos. Accrual as of 2-7-19 is 1,164 (71.1%). Contacts: Protocol: CTSU member website https://www.ctsu.org . Questions: NRG Oncology Pgh Clin Coord Dpt: 1-800-477-7227 or ccd@nsabp.org . Pt entry: OPEN at https://open.ctsu.org or the OPEN tab on CTSU member website. Support: U10 CA-2166; -180868, -180822; 189867; Elekta NCT01872975 Clinical trial information: NCT01872975.

Abstract Background Although ESCrE are a global challenge, data on ESCrE in low- and middle-income countries are limited. In particular, colonization data are critical for larger antibiotic resistance efforts. We characterized the colonization prevalence of ESCrE in various settings in Botswana. Methods This study was conducted in 3 hospitals and 6 clinics located in 3 districts in Botswana. In each hospital, we conducted surveillance of adult patients. Adult clinic patients were also randomly selected for participation. Finally, we enrolled community subjects by inviting each enrolled clinic subject to refer up to 3 adults. Each adult clinic or community subject was also allowed to refer their children. All subjects had rectal swabs obtained which were inoculated onto chromogenic media for preliminary identification of ESCrE. Final identification and susceptibility testing were performed using MALDI-TOF MS and VITEK-2, respectively. Genotyping was done for identification of extended-spectrum beta-lactamase (ESBL) genes. Results Enrollment occurred from 1/15/20-9/4/20 but paused from 4/2/20-5/21/20 due to a countrywide COVID lockdown. Of 5,088 subjects approached, 2,469 (49%) participated. Enrollment by subject type was: hospital – 469 (19%); clinic – 959 (39%); community adult – 477 (19%); and community child – 564 (23%). Of 2,469 subjects, the median (interquartile range) age was 32 years (19-44) and 1,783 (72%) were female. 759 (31%) subjects were colonized with at least one ESCrE; 130 subjects were colonized with multiple strains. E. coli (n=663) and K. pneumoniae (n=121) were most common. ESCrE colonization prevalence was 43% for hospital subjects, 31% for clinic subjects, 24% for adult community subjects, and 26% for child community subjects (p< 0.001)). ESCrE prevalence varied significantly across regions (Figure 1) and was significantly higher pre-lockdown vs post-lockdown (Figure 2). CTX-M was the most common ESBL gene (Figure 3). Figure 1. ESCrE Colonization - Study Sites Figure 2. ESCrE Colonization - Temporal Trends Figure 3. ESCrE Genotypic Analyses Conclusion ESCrE colonization was common in both healthcare and community settings in Botswana. Colonization prevalence varies by region and clinical setting and decreased following a countrywide lockdown. These findings provide important clues regarding potential drivers of ESCrE that might serve as targets for intervention. Disclosures Robert Gross, MD, MSCE, Pfizer (Other Financial or Material Support, Serve on DSMB for drug unrelated to HIV) Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))

This is a descriptive type of cross sectional study among 477 family heads as respondents. It is aimed to identify morbidity pattern, duration of illness among households' members and also to determine treatment seeking behavior during illness. The socio-demographic characteristics of the respondents are points of investigations. It reveals from the findings that the mean age of the respondents is 35.16 years. They are mostly female (66%) and married (90%). Only 30% respondents are illiterate, 69% respondents are found from nuclear family. The study shows 73% respondents family are suffering from illness during last two months and majority sufferers (19%) and (44%) were less than 5years and more than 31 years old respectively. However, male sufferers were more among <5 years (9.63%) and female sufferers more (26.84%) among >31 years old. Moreover about 43% respondents' family members are suffering for more than 4 weeks and about 29% less than 01 week. On the other hands, Fever, Cough and Pain are found prominent sign/symptoms among 38%, 28% and 29% sufferers respectively. Common cold, Arthritis and Diarrhoea are found as diagnosis among 53.5%, 22.5% & 8.5% respondents' family members respectively. Nevertheless majority 56% are seeking treatment from MBBS doctors. The study findings highlight awareness program among family heads and adult sufferer towards preventing infectious and chronic diseases as well as to undertake modern scientific treatment. Improved surveillance system in the locality may be considered for early detection of cases to treat accordingly to avoid complications. DOI: http://dx.doi.org/10.3329/akmmcj.v3i2.11686 AKMMC J 2012: 3(2): 06-10

7050 Background: Treatment of older pts with AML is often complicated by comorbidities and pts with comorbidities are often underrepresented in clinical trials. The HCT-CI, which was developed in pts receiving allogeneic SCT, has been applied to pts receiving induction therapy for AML in an effort to assist in therapeutic and investigational decisions (Kantarjian 2006; Etienne 2007; Giles 2007). HCT-CI scores have been shown to be predictive of early death and survival in pts ≥ 60 years receiving induction therapy for AML, with early death rates of 3%, 11%, and 29% for pts with HCT-CI scores of 0, 1–2, and ≥ 3, respectively (Giles 2007). Methods: 140 pts age ≥ 60 with poor risk de novo AML from two phase II studies were scored for comorbidity by HCT-CI. In these studies, poor risk was defined by the presence of at least one risk factor: age ≥ 70, ECOG PS = 2, unfavorable cytogenetics, or cardiac, pulmonary, or hepatic dysfunction. All pts received induction therapy with 600 mg/m2 laromustine as a single 30–60 min infusion. A second induction cycle could be administered to pts with PR or hematologic improvement. Pts with CR or CRp were able to receive consolidation with laromustine 400 mg/m2 (Study CLI-033) or araC 400 mg/m2/day CIV for 5 days (Study CLI-043). Results: HCT-CI score was 0 in 7 (5%) pts, 1–2 in 19 (14%), and ≥ 3 in 114 (81%). The median HCT-CI score was 5 (range 0–13). The most common comorbidities were cardiac (42%), severe pulmonary (39%), infection (35%), and arrhythmia (31%). 52 (37%) of all pts achieved a CR/CRp; 39/114 (34%) of pts with HCT-CI score ≥ 3 achieved a CR/CRp. Deaths within 30 days of first induction were observed in 0/7 pts with HCT-CI score 0, 4/19 (21%) with score 1–2, and 16/114 (14%) with score ≥ 3. Overall survival at 12 months was 43%, 14%, and 21% for pts with HCT-CI scores of 0, 1–2, and ≥ 3, respectively. Conclusions: The majority (81%) of these older poor risk AML pts treated with laromustine had a HCT-CI score ≥ 3, confirming the poor risk nature of this patient group. The induction death rate for pts treated with laromustine and with HCT-CI score ≥ 3 was lower than that reported for a group of pts with HCT-CI score ≥ 3 treated with standard induction chemotherapy (14% vs 29%; Giles 2007). [Table: see text]

Abstract Iron overload, a potentially serious consequence of multiple blood transfusions, can be effectively managed with chelation therapy. Deferasirox, an investigational once-daily oral chelator, has been evaluated in a 1 year study of iron-overloaded adult and pediatric patients (n=184) with transfusion-dependent anemia including β-thalassemia, myelodysplastic syndromes (MDS) and Diamond-Blackfan anemia (DBA). Patients were stratified into four daily dose groups (5, 10, 20 and 30 mg/kg) according to baseline liver iron concentration (LIC; 2–3, &gt;3–7, &gt;7–14 and &gt;14 mg Fe/g dw, respectively). Iron balance was determined for all patients, based on transfusional iron intake and chelator-induced iron excretion, derived from the change in LIC during the study (Table 1). Patient characteristics, LIC, serum ferritin and iron excretion/intake ratio during deferasirox treatment β-thalassemia (n=85) DBA (n=30) MDS (n=47) Other anemias (n=22) *Mean ± SD Age*, years 24.7 ± 10.0 16.1 ± 10.3 65.1 ± 12.5 35.8 ± 22.9 Body weight, kg 51.1 ± 14.1 39.1 ± 18.7 70.4 ± 12.5 56.1 ± 18.5 Deferasirox dose*, mg/kg 23.8 ± 7.2 23.6 ± 7.4 20.0 ± 8.3 21.9 ± 6.5 Iron intake*, mg/kg/day 0.35 ± 0.12 0.40 ± 0.11 0.28 ± 0.14 0.31 ± 0.19 &lt;0.3, n (%) 28 (33) 6 (20) 25 (53) 10 (45) 0.3–0.5, n (%) 49 (58) 19 (63) 20 (43) 7 (32) &gt;0.5, n (%) 8 (9) 5 (17) 2 (4) 5 (23) Serum ferritin*, ng/mL Baseline 4321 ± 2881 3245 ± 2439 3343 ± 1978 3144 ± 1850 Absolute change −386 ± 1626 −118 ± 1373 −268 ± 2053 −750 ± 1517 LIC*, mg Fe/g dw (n=76) (n=26) (n=28) (n=17) Baseline 19.3 ± 10.9 18.8 ± 10.7 15.6 ± 11.9 15.1 ± 6.2 Absolute change −4.7 ± 8.6 −1.6 ± 6.5 −5.7 ± 6.3 −3.7 ± 6.3 Iron excretion/intake ratio 1.5 ± 0.90 1.1 ± 0.46 1.7 ± 0.93 1.6 ± 1.48 Transfusion requirements and iron intake during the study varied widely between diseases. However, LIC and serum ferritin decreases were consistently achieved in all patient groups. More than one-third (38%) of patients, most of whom had MDS or other anemias, had an iron intake rate &lt;0.3 mg/kg/day (average: 0.2 mg/kg/day; corresponding to 5.6 ml RBC/kg/month). In these patients, deferasirox at 10 and 20 mg/kg reduced LIC. Overall, an iron intake- and dose-related response pattern was observed for both LIC and serum ferritin (Figure 1). Effect of deferasirox dose and iron intake on changes in serum ferritin and LIC over 1 year Effect of deferasirox dose and iron intake on changes in serum ferritin and LIC over 1 year According to these results, deferasirox demonstrates the ability to stabilize and effectively decrease body iron levels at doses of 10, 20 and 30 mg/kg/day, depending on the degree of iron intake. In conclusion, dosing of chelation therapy should be guided by a patient’s transfusion requirements and the treatment goal, which is either to maintain or reduce body iron.

Abstract Introduction: BP of PV presents with dyserythropoiesis, including ring sideroblasts, and bilineage dysplasia in most cases. Clonal evolution or acquisition of new cytogenetic clone(s) plays a critical role in progression to BP of PV. SF3B1 mutation is associated with 75% of MDS with ring sideroblasts (RS). We hypothesized that an increase in ring sideroblast counts is an early event in the BP evolution. We postulate that genomic lesions other than in splicing factors genes are implicated in RS development in PV during BP evolution. Methods: We identified all cases in the last 14 years (2004 - 2018) with a diagnosis of PV in the MDACC files. We collected demographic, clinical, morphological, cytogenetic, and NGS information from 61 patients who developed BP progression from PV. We did an assessment and scoring of all bone marrow (BM) samples available at BP evolution. Results: A total of 61/477 (13%) patients with diagnosis of BP of PV were identified. Median age at BP diagnosis was 67 yrs. (32-82). This included 34 (56%) men and 27 (44%) women. At BP presentation, median BM blast percentage was 28%; 51 (84%) patients had BM dysplasia; 35 patients (69%) with dyserythropoiesis, 22 (43%) cases showed bilineage dysplasia. At BP, 43 pts had complex CG, 9 were were normal karyotype, 3 had double and 5 had single abnormalities. Prussian blue stain for Iron evaluation was available in 54 patients (89%); 24 patients (44%) had 0% RS; 19 patients (35%) had 1-14% RS; and 11 pts (20%) had >15% RS. Mutation analysis for splicing factor was performed on 13 patients. Of these, 2 patients with >15% RS had SRSF2 mutation and 1 patient with 6% RS had SF3B1 mutation. The other patients were wild type for SF3B1, SRSF2, U2AF1 (5 patients: >15% RS, 2 patients: 1-14% RS and 3 patients: 0% RS). Twenty-four (39%) patients had BM available before the BP diagnosis; median time between first BM at MDACC and BP BM diagnosis was 35 months (range, 1-135). At Baseline BM assessment, median BM blast was 3%; 13 (54%) patients had BM dysplasia. Prussian blue stain for Iron evaluation was available in 13 pts (55%): 10 pts (77%) had 0% RS and 3 pts (23%) had 1, 3, and 60% RS, respectively. To evaluate the level of RS during disease evolution we identified 10/26 pts who had at least 1 BM sample available between the first BM and the BP. 5/10 pts were in spent phase with increased blast, multilineage dysplasia and complex CG (RS: 6%, 25%, 0%, 1% and 50%) median time between samples 5 months. 4/10 pts had 1-4% blast, isolated dyserythropoiesis and normal diploid CG (RS: 12%, 5%, 2% and 0%). The median time between samples was 56 months. The last pt. had 0% blast, no dysplasia, del(20q) on CG and no RS. Pt. developed BP of PV 41 months after this follow up sample. Ten pts with PV chronic phase and were used as control group, median follow up of 14,5 yr. None of the patients had RS at baseline or at last follow up BM. Median time between samples 6 yrs. RS increase during PV evolution were statistically significant more frequent in pts who develop BP than in pts who remain in chronic phase of PV (7/10 vs. 0/10. P=0.003) Conclusion: Splicing factor gene mutation is infrequent in BP of PV despite the presence of dyserythropoiesis and frequent RS in 55% of patients. When present , RS may identify disease evolution and correlate with the disease phase of PV before BP. Dyserythropoiesis and the acquisition of RS is an early event BP of PV that precede other markers of disease progression like CG. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 4093 Introduction: Relapse remains a major cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological diseases. During the last decade, many improvements have been achieved in the understanding of the disease- and patient-related conditions in order to obtain the optimal allogeneic effect but the relapse is still representative which leaded to the development of different chemo- and immuno-therapy strategies. Aims: To evaluate at a first time the different pre- and post-transplantation factors impacting the relapse occurrence after allo-HSCT, and at a second time, to evaluate factors impact the survival post-relapse including the different treatment options. Material and methods: We have retrospectively studied the occurrence of relapse in 345 patients, 198 (57%) males and 147 (43%) females with a median age of 43 years (range17–66) who received allo-HSCT at our institution for hematological malignancies between years 2000 and 2011; 205 (59%) from siblings donors and 140 (41%) form unrelated donors. At transplantation, there were 148 (43%) patients in first complete response or first chronic phase (CR1/CP1), 66 (19%) in CR2/CP2 and 131 (38%) < CR2/CP2. Two hundred and six (60%) patients received a full intensity conditioning and 139 (40%) a reduced intensity one. The different patients and transplantations characteristics are detailed in Table 1. Results: After HSCT, 336 (97%) patients engrafted. The cumulative incidence of acute GVHD≥2 at 3 months was 35% (95%CI 32–37); the cumulative incidence of extensive and limited chronic GVHD at one year was the same 15% (95%CI 13–17). After a median follow-up of 11.4 months (range 4–129), the median overall survival (OS) for the whole population was 19 months (range 12–33) with a 2-years probability of 47% (95%CI 42–53). Eighty eight (25.5%) patients relapsed with a cumulative incidence at one and two years of 19% (95%CI 17–21) and 22% (95%CI 20–24) respectively. Characteristics of relapsed patients are described in Table 1. After relapse, 65 (74%) patients were treated [21 (32%) received donor lymphocyte infusion (DLI) alone, 21 (32%) chemotherapy alone, 14 (22%) DLI + chemotherapy and 9 (14%) received other treatment] and 23 (26%) were not treated due to deadly relapse. The median OS from relapse was 4 months (range 3–5) and the one year probability of OS in patients who relapsed was 21% (95%CI 14–31). The multivariate analysis studying the impact of different variables on the occurrence of relapse showed a negative impact of disease status [<CR/CP: HR=3.9 (2.4–6.7), p=0.0001], a negative impact of CMV status [D+R-: HR=2.4 [1.2–4.7], p=0.009] and a protective impact of cGVHD [HR=0.37 (0.2–0.6), p=0.0002]. The multivariate analysis studying the pre- and post-relapse variables on the survival after relapse showed a positive impact of ABO incompatibility [Major ABO incompatibility: HR=0.39 (0.16–0.9), p=0.03], a negative impact of disease status [<CR/CP: HR=2.4 (1.3–4.4), p=0.003] and a positive survival outcome in patients receiving DLI with or without chemotherapy [HR=0.5 (0.3–0.8), p=0.005]. Conclusion: We showed that relapse after allo-HSCT in hematological malignancies is still a significant issue, disease status at HSCT and CMV matching worsen its occurrence while cGVHD can be protective. Survival rate after relapse is still very low reflecting the difficulty to find an optimal treatment, disease status at transplantation seem to have a long term effect while the use of DLI with or without chemotherapy can offer better results. In addition to the new chemotherapy molecules, immunotherapy should be used in order to enhance the graft-versus-leukemia effect not only after relapse, but also early in presence of a minimal residual disease. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Autologous hematopoietic progenitor cells (auto-HC) can be mobilized either by hematopoietic growth factors (GF) alone or cytotoxic chemotherapy + GF (CC+GF). The latter is associated with higher CD34+ yields, but is associated with increased costs and risks of infection and hospitalization. In patients with multiple myeloma (MM) undergoing Auto-HCT, it is uncertain whether mobilization with CC+GF affects post transplant outcomes. Methods: We conducted a retrospective analysis of patients with MM undergoing their first AHPCT following high dose melphalan (≥140 mg/m2) between 2007 and 2012 in US and Canada and registered with the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients who had a planned subsequent allogeneic transplant, received VAD or similar induction therapy, had disease progression prior to transplant, or were mobilized with plerixafor were excluded from the analysis. The primary endpoint was progression-free survival (PFS) and the main secondary end-points were transplant-related mortality (TRM), relapse and overall survival (OS). Results: There were 519 patients in GF and 449 in CC+GF with median follow-up of 42 and 46 months respectively. The most common mobilizing CC regimen was single agent cyclophosphamide (71%). GF and CC+GF groups were similar but there were more patients in GF with only one prior line of therapy, lenalidomide exposure and CR at the time of transplant and more patients in CC+GF with low HCT co-morbidity index, prior thalidomide exposure and planed second autologous transplant (Table 1). Median number of days for auto-HC collection was 2 (IQR 1-3) in GF and 1 (IQR 1-3) in CC+GF (P<0.001). There were fewer days between collection and transplant (median 16 vs. 18, P<0.001) and fewer CD34+ cells (x 106/kg) infused at transplant (median 3.9, IQR=3.1-4.8, vs. 5.1, IQR 3.5-6.9, P<0.001) in GF than in CC+GF. Kinetics of neutrophil engraftment (> 0.5 x 109/L) was similar between groups (13 vs. 13 days, P=0.69) while platelet engraftment (> 20 x 109/L) was faster in CC+GF (median 19 vs. 18 days, P=0.006). There was no difference between groups in number of hospitalization days (14 vs. 14, P=0.7). In univariate analysis, there was no significant difference between the two groups in OS, PFS, or TRM. In multivariate analysis, stage III at diagnosis and Karnofsky status <90 but not modality of mobilization were associated with worse PFS. Similarly HCT-CI >2, Stage III at diagnosis and immunoglobulin isotype (IgG/IgA/Others), but not mobilization were associated with OS. Adjusted 3-years PFS was 43% (95% C.I. 38-48) in GF and 40% (95% C.I. 35-45) in CC+GF, P=0.33 (Figure). Adjusted 3-years OS was 82% (95% C.I. 78-86) vs 80% (95% C.I. 75-84), P=0.43 and adjusted 5-year OS was 62% (95C.I. 54-68) vs. 60% (95% C.I. 52-67), P=0.76, for GF and CC+GF respectively (Figure). Conclusions: MM patients undergoing AHPCT have similar outcomes irrespective of the use of cytotoxic chemotherapy mobilization. We found no evidence that chemotherapy mobilization contributes to disease control in MM. Table Characteristics of patients and treatments GF CC+GF P N=519 N=449 Lines of therapy <0.001 1 382 (74) 265 (59) 2 113 (22) 136 (30) >2 24 (5) 48 (11) Prior therapy <0.001 Thalidomide+Bortezomb+-Steroid 74 (14) 92 (20) Lenalidomide+Bortezomb+-Steroid 121 (23) 48 (11) Thaildomide+-Steroid 85 (16) 106 (24) Bortezomib+-Steroid 132 (25) 136 (30) Lenalidomide+-Steroid 107 (21) 67 (15) Disease status at HCT 0.05 CR 84 (16) 48 (11) PR 407 (78) 378 (84) MR/NR/SD 28 (5) 23 (4) HCT-CI 0.006 0 227 (44) 227 (51) 1-2 147 (29) 134 (30) >2 145 (28) 88(20) Time from diagnosis to HCT <0.001 <6 mo 221 (43) 140 (31) 6-12 mo 298 (57) 309 (69) Year of HCT 0.03 2007-2008 289 (56) 272 (61) 2009-2010 105 (20) 100 (22) 2011-2012 125 (24) 77 (17) Melphalan dose 0.40 140-180 mg/m2 71 (14) 70 (16) >180 mg/m2 448 (86) 379 (84) Transplant type 0.02 Single transplant 417 (80) 331 (74) Multiple Transplants Planned 2ndAuto (0-6 mo) 42 (8) 63 (14) Planned 2ndAuto (>6 mo) 5 (1) 6 (1) Use of maintenance agent 198 (38) 176 (39) 0.29 Figure 1 Figure 1. Disclosures Costa: Sanofi: Honoraria.

Abstract Abstract 3099 Background: Despite the fact that allogeneic SCT currently offers patients with high risk AML the best chance of cure, we've aimed to investigate the outcome of AML patients who have undergone ASCT in our center, considered as one of spanish reference hospital in SCT, and the parameters that have been able to influence in relapse rate (RR), overall survival (OS) and relapse free survival (RFS). Methods: Retrospective study in 121 AML patients who have undergone ASCT between 1988 and 2010. The analysis has been performed in 95 patients (50 male and 45 female) by excluding 26 acute promyelocitic leukemias (APL): 62 patients until 1999 and 33 since 2000. Median age was 45 [18–74] and median lecocyte count, 17250/μL [1000–318000]. 90% were “de novo” AML and 92% were in first complete remission (1°CR). Cytogenetic risk was as follows: 64% intermediate, 29% high and 7% low. Conditioning regimens were oral BuCy (62%), CyTBI (24%) and intravenous BuCy (12%). Stem cell source was bone marrow (BM) in 46 patients (48%), but the use of peripheral blood (PB) was generalized since 1997. Colony-stimulating factors were used in 52% of total patients. Median time from last treatment was 94 days [30–285]. Results: The median follow-up of this study was 125 months [0–216]. OS at 1, 3 and 5 years were 59%, 46% and 44%. RFS at 1, 3 and 5 years were 60%, 49% and 48%. There was no relapse after 5 years from ASCT. Early mortality (before day +100) was 12% (9 in 11 patients between 1988 and 1999) and late mortality was 47% (34 in 45 patients because of relapse, with no significant difference between 1988–1999 and 2000–2010). Secondary malignancies incidence was 13% (5 in 6 patients suffered from haematologic neoplasms: 4 MDS at 43, 89, 90 and 97 months and 1 Follicular Lymphoma at 50 months), median age of these patients was slightly higher (53, 5 years old) and none of them had received TBI. Multivariable analysis showed that RFS at 5 years was influenced by: disease status at ASCT (55% if 1°CR vs 0% if ≥2°CR/PR/refractory disease, p<0, 0001), leucocyte count at diagnosis (p<0, 0001, without a significant cut-off), ethiologic classification (53% if “de novo” AML vs 19% if secondary AML, p=0, 002), age of recipient (60% if younger than 40 years old vs 45% if older, p=0, 031) and year of ASCT (62% if 2000–2010 vs 44% if 1988–1999, p=0, 043). Other parameters as stem cell source, conditioning regimen or cytogenetic risk had no significance in univariable analysis. Relapse was influenced by the presence of minimal residual disease (MRD) at time of ASCT (p=0, 03, with available data in 47 patients, only since 1997) and by a CD34 cells count higher than 3 × 106/kg (p=0, 04, with available data in 49 patients, only in case of PB as stem cell source). Conclusions: ASCT is an effective procedure of cure in AML patients (global RFS of 48% at 5 years), even in high cytogenetic risk (38% with no significant difference), offering its best outcomes in young patients diagnosed of “de novo” AML without hyperleucocytosis, who have undergone the transplantation in 1°CR since 2000. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction. The application of Pediatric-Type Therapy (PTT) programs to adults with ALL can improve outcome significantly despite higher age-related toxicity. Recent series reported survival rates ≥ 50%, but only few combined PTT with Minimal Residual Disease (MRD) study for risk-oriented Hematopoietic Cell Transplantation (HCT) and/or explored the value of specific PTT element such as higher dose, lineage-targeted MTX up to 5 g/m2. Methods. To improve over prior data, NILG protocol 10/07 (Clinical.Trials.gov NCT-00795756) for unselected adult patients aged 18-65 years combined PTT together with MRD study for risk/MRD-based HCT. The 8-course program consisted of a 5-drug complete remission (CR) induction (cycle no. 1; imatinib added if Ph+) followed by 3 modified BFM blocks (no. 2, 4 and 6), 3 lineage-targeted MTX blocks (no. 3, 5 and 7; MTX 5 g/m2 for T-ALL and 2.5 g/m2 for B-ALL [1.5 g/m2 if age > 55 years or Ph+]; no. 3 and 7 with high-dose Ara-C 2 g/m2 x4, no. 5 with L-Asp 10,000 IU/m2 x2) and reinduction (no. 8). CNS prophylaxis was with triple intrathecals or liposomal cytarabine (Haematologica 2015;100:786). MRD was studied molecularly with sensitive probe(s) (sensitivity 10-4 or greater) on marrow samples obtained at end of induction (week 4, w4) and after cycles 3 (w10), 5 (w16), 7 (w22) i.e. after 1st, 2nd and 3rd lineage-targeted MTX block. Patients were risk-stratified at diagnosis and after MRD analysis for the purpose of allocation to HCT or conventional maintenance. The HCT allocation cohort consisted of predefined very high-risk patients (vHR: WBC >100, highly adverse cytogenetics, pre-T/mature T-ALL) regardless of MRD, of HR patients without MRD study (HR: late CR; B-ALL with WBC >30 or pro-B phenotype), and of HR or standard-risk (SR) patients with MRD ≥ 10-4 at w10/16 or positive at w22. Conversely, the maintenance allocation cohort consisted of SR and HR patients with MRD < 10-4 at w10/16 and negative at w22 and of SR patients without MRD study. A family related/unrelated donor search was activated at diagnosis in order to proceed to HCT soon after cycle no. 3 when needed. Results. 205 patients were enrolled, with a median age of 41 years (range 17-67 years, 11% > 60 years). 55% were male, 42 had Ph+ ALL, 119 Ph- B-ALL and 44 T-ALL. Of 163 patients with Ph- ALL, 45% were SR, 13% HR and 42% vHR. CR rate was 98% in Ph+ ALL and T-ALL, and 83% in Ph- B-ALL (88% vs 58% in patients ≤ vs > 60 years, P .0013). The MRD study was successful in 109/142 CR patients with Ph- ALL (77%), contributing to the final risk classification in 63 patients, of whom 41 were MRD responsive (65%) and 22 MRD resistant (35%). Altogether, 55 CR patients constituted the maintenance allocation group (39%) and 87 the HCT allocation group (61%), which included mainly vHR patients (n=61, 43%) selected for HCT independently of MRD study results. According to intention-to-treat, median OS is not reached (53% at 5 years, figure) and median DFS is 4.8 years (48% at 5 years). In Ph- ALL, 5-year OS/DFS are 74%/61% in T-ALL (medians not reached) and 48% each in B-ALL (medians 3.9 and 4.7 years). Median OS is not reached in both HCT and maintenance allocation groups (58% and 73% at 5 years, respectively, P .078), with a median DFS of 4.7 years (48% at 5 years) versus not reached (59% at 5 years) (P .19). Treatment adherence was good with some exceptions in maintenance allocation group (6 HCT, 11%) and a transplant realization of 68% (53 allogeneic; 6 autologous) in HCT allocation group. With HCT, 5-year incidence of nonrelapse mortality was 17%. The MRD analysis proved that DFS of patients achieving an MRD response <10-4 at w4 (n=46/90, 51%) or w10 (n=76/107, 71%) was significantly improved compared to those with MRD ≥ 10-4, with median not reached and 5-year rate 67% versus 4.5 years and 41% (w4 MRD; P .041), and 7.2 years and 64% versus 1 year and 23% (w10 MRD; P .0001). Conclusion. The current PTT and MRD-based risk-oriented strategy was applicable to adults with ALL in a wide age range, with some limitations in patients > 60 years. 5-year OS and DFS of 55% and 52% respectively in Ph- patients aged up to 65 years represent an improvement over prior NILG study (5-year OS and DFS of 36% and 35% respectively). MRD was essential in orientating the HCT choice in SR and HR patients and retained a major prognostic role in all patients. Optimizing the early MRD response with new immunotherapeutics and clarifying the role of HCT in MRD responsive vHR patients are some relevant topics of future research. Figure Figure. Disclosures Ciceri: MolMed SpA: Consultancy. Vitolo:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gallamini:Millenium Takeda: Membership on an entity's Board of Directors or advisory committees.

Background:In the Phase 3 DISCOVER-11 & DISCOVER-22 trials, guselkumab (GUS), a human monoclonal antibody targeting the IL-23p19-subunit, was effective in psoriatic arthritis (PsA) across joint & skin endpoints. At Week 24 (W24), GUS benefit was consistent regardless of baseline (BL) demographic & disease characteristics.3Objectives:We assessed whether GUS efficacy was sustained through W52 in pooled DISCOVER-1 & -2 patients (pts) across select BL subgroups.Methods:Adults with active PsA despite standard therapies were enrolled in DISCOVER-1 (swollen [SJC] ≥3 & tender joint count [TJC] ≥3, C-reactive protein [CRP] ≥0.3 mg/dL) & DISCOVER-2 (SJC ≥5 & TJC ≥5, CRP ≥0.6 mg/dL). 31% of DISCOVER-1 pts had received 1-2 prior tumor necrosis factor inhibitors; DISCOVER-2 pts were biologic naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). Pts randomized to PBO received GUS 100 mg Q4W starting at W24 & were excluded from these analyses assessing maintenance of effect from W24 to W52. GUS effects on joint (American College of Rheumatology [ACR]20/50/70) & skin (Investigator’s Global Assessment [IGA=0/1 + ≥2-grade reduction from W0] in pts with ≥3% body surface area [BSA] with psoriasis & IGA ≥2 at W0) endpoints were evaluated by pt BL SJC, TJC, conventional synthetic disease-modifying antirheumatic drug (csDMARD) use, body mass index (BMI), PsA duration, & % BSA with psoriasis. Missing data were imputed as nonresponse through W52.Results:BL pt characteristics in DISCOVER-1 (N=381) & DISCOVER-2 (N=739) were well balanced across randomized groups.1,2 Among 1120 pooled pts, mean SJC was 11, mean TJC was 21, & 68% used csDMARDs (primarily methotrexate [MTX]). At W24, 62% (232/373) & 60% (225/375), respectively, of GUS Q4W- & Q8W-treated pts achieved ACR20 vs 29% (109/372) of PBO, with GUS effect consistently observed across pt BL subgroups (Figure 1). ACR20 response rates were sustained or increased at W52 in the GUS Q4W (72%) & Q8W (70%) groups & across SJC (61-79%), TJC (68-76%), & csDMARD use (68-80%) subgroups (Table 1) & pt subgroups defined by BL BMI, PsA duration, & % BSA with psoriasis (data not shown). ACR50 & 70 response patterns were similar to ACR20 (Table 1). In pts with ≥3% BSA psoriasis & IGA ≥2 at BL, 71% (193/273) & 66% (171/258) of GUS Q4W- & Q8W-treated pts, respectively, vs 18% (47/261) of PBO, achieved IGA 0/1 at W24, with GUS effect consistently observed across pt BL subgroups (Figure 1). IGA 0/1 response rates were also sustained or increased at W52 in the GUS Q4W (80%) & Q8W (71%) groups & across % BSA with psoriasis (67-87%) & csDMARD use (68-87%) subgroups (Table 1) & pt subgroups defined by BL BMI and PsA duration (data not shown).Conclusion:Treatment with GUS 100 mg Q4W & Q8W resulted in sustained improvement in signs & symptoms of active PsA through W52 regardless of pt BL characteristics.References:[1]Deodhar A, et al. Lancet 2020;395:1115-25;[2]Mease P, et al. Lancet 2020;395:1126-36;[3]Deodhar A, et al. American College of Rheumatology 2020; Poster P0908.Figure 1Figure 1Table 1.ACR & IGA Responses at Weeks 24 & 52 & by Select BL CharacteristicsGuselkumab Q4WGuselkumab Q8WN=373N=375Week 24Week 52Week 24Week 52ACR20, %62726070 SJC (<10/10-15/>15)68/59/5379/61/6757/66/6068/68/76 TJC (<10/10-15/>15)74/67/5673/76/6962/60/6075/68/68 csDMARD use (none/any/MTX)66/60/6380/68/6862/59/5773/68/68ACR50, %34493145 SJC (<10/10-15/>15)41/32/2058/39/3834/28/2646/40/49 TJC (<10/10-15/>15)51/41/2458/53/4340/33/2652/46/43 csDMARD use (none/any/MTX)36/33/3553/46/4836/29/2751/42/40ACR70, %16271627 SJC (<10/10-15/>15)22/10/732/20/2418/10/1930/23/26 TJC (<10/10-15/>15)29/19/934/32/2227/15/1435/28/24 csDMARD use (none/any/MTX)21/13/1430/26/2721/14/1434/24/23N=273N=258IGA 0/1, %71806671 BSA % with psoriasis(≥3-<10/≥10-<20/≥20)61/71/8076/87/7962/64/7267/72/74 csDMARD use (none/any/MTX)84/64/6787/77/7872/63/6477/68/68Disclosure of Interests:Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB Pharma, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Celgene, Janssen, Leo, Eli Lilly, Novartis, UCB Pharma, Consultant of: AbbVie, Almirall, Celgene, Janssen, Leo, Eli Lilly, Novartis, UCB Pharma, Grant/research support from: Pfizer, John Tesser Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Crescendo Biosciences/Myriad, GlaxoSmithKline, Genentech, Janssen, Eli Lilly, and Pfizer, Consultant of: AbbVie, AstraZeneca, Bristol Myers Squibb, Gilead, Janssen, Eli Lilly, Novartis, and Pfizer, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Horizon, Janssen, Eli Lilly, Merck KG, Novartis, Pfizer, Sandoz, Sun Pharma, Setpoint, and UCB Pharma, Elena Schiopu Consultant of: Janssen, Grant/research support from: Janssen, Soumya D Chakravarty Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Global Services, LLC, Yusang Jiang Employee of: Cytel, Inc., providing statistical support (funded by Janssen), Shihong Sheng Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Iain McInnes Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB Pharma, Atul Deodhar Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, UCB Pharma.

Background: Clinical and analytical data on patients suffering from coronavirus disease-2019 (COVID-19) indicate that endothelial damage plays a key role in the pathophysiology of the disease and is responsible for the pulmonary complications and the thrombotic microangiopathy affecting multiple organs, which contribute directly to mortality (Ackerman et al. N Engl J Med 2020). Detection of biomarkers of endothelial injury in circulating blood may provide critical diagnostic and prognostic information on the disease course (Goshua et al. Lancet Haematology 2020). Endothelial injury is also a cornerstone of pathobiology in other septic and potentially life-threatening inflammatory syndromes. Objectives: To identify circulating markers of endothelial damage in COVID-19 patients, and compare their levels with those observed in other septic syndromes. Methods: Plasma samples from non-critically ill patients with confirmed COVID-19 pneumonia (positive nasopharyngeal swab and confirmatory radiological chest imaging) requiring admission (n=42) were collected during the first 36h of hospitalization. Endothelial damage was evaluated by measuring in plasma: i) markers of endothelial function and activation (sVCAM-1, VWF, ADAMTS-13 activity, Protein C and α2-antiplasmin as a marker of fibrinolysis); ii) heparan sulfate (HS) levels, as indicators of endothelial glycocalyx degradation and loss of endothelial barrier function; and iii) C5b9 deposits on endothelial cells in culture, and soluble C5b9 (sC5b9) levels, to measure complement activation. Circulating dsDNA was analyzed as an indicator of the presence of neutrophil extracellular traps (NETs). ELISA tests were used for sVCAM-1, Protein C, HS, and sC5b9 levels. ADAMTS-13 activity was evaluated by FRETS. VWF, Protein C, and α2-antiplasmin were measured at the Atellica COAG 360 (Siemens Healthineers). C5b9 deposits were assessed by immunofluorescence and dsDNA levels by Quant-iT PicoGreen assay kit. Results were compared with those obtained in healthy donors (controls, n=45), and patients with non-infectious systemic inflammatory response syndrome (NI-SIRS, n=8) and septic shock (SS, n=8). Results: Levels of sVCAM-1 were significantly higher in COVID-19 patients vs. controls, NI-SIRS and SS (159±12 vs. 79±4, 57±8 and 80±10 ng/mL, respectively, p&lt;0.005) (Mean±SDM). VWF was elevated in COVID-19 patients vs. controls (240±26 vs. 96±5%, p&lt;0.001), with similar values in NI-SIRS (271±40%), and significantly reduced vs. SS (476±43%, p&lt;0.001). HS levels in COVID-19 patients were twice those detected in controls (1669±174 vs. 839±36 ng/mL, p=0.001), but they did not differ from those in NI-SIRS (1372±368 ng/mL), and were significantly lower than in SS (3677±880 ng/mL, p&lt;0.001 vs COVID-19). Regarding complement activation, deposits of C5b9 on endothelial cells were significantly increased vs. controls (2-fold, p&lt;0.01), with no notable differences vs. NI-SIRS (3±1-fold) and significantly lower than in SS (8±2-fold, p&lt;0.001). Remarkably, sC5b9 levels were much more elevated in COVID-19 patients (1064±120 vs. 204±11 ng/mL, p&lt;0.001), and no significant differences were observed vs. NI-SIRS (902±160 ng/mL) or SS (958±180 ng/mL). Also of note, presence of NETs was significantly elevated in the plasma of COVID-19 patients vs. controls (16±1.3 vs. 2±0.3 ng/ml, p&lt;0.001), but similar to NI-SIRS (19±5 ng/mL) and clearly inferior to SS (33±6 ng/mL, p&lt;0.001) (Figure). Importantly and in contrast, ADAMTS-13 activity, Protein C, and α2-antiplasmin values were within the normal range in COVID-19 patients. Conclusions: Our data clearly demonstrate the presence of endothelial stress products in the circulating blood of non-critically ill COVID-19 patients. These biomarkers of endothelial injury are suggestive indicators of different aspects of the disease: specifically, release of acute phase reactants, degradation of the endothelial cell glycocalyx, and activation of the complement system. Furthermore, this profile of biomarkers in COVID-19 appears specific, with a differential behavior in comparison with septic shock, in which endothelial damage is also known to be critical. Additional studies are needed to validate these biomarkers as diagnostic and prognostic tools of the endothelial complications in COVID-19 patients, both in early disease and later, as well as supporting specific forms of therapeutic intervention. Figure Disclosures Carreras: Jazz Pharmaceuticals: Research Funding, Speakers Bureau; German Jose´ Carreras Leukaemia Foundation: Research Funding. Carlo-Stella:Boehringer Ingelheim and Sanofi: Consultancy; ADC Therapeutics and Rhizen Pharmaceuticals: Research Funding; Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca: Honoraria; Servier, Novartis, Genenta Science srl, ADC Therapeutics, F. Hoffmann-La Roche, Karyopharm, Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Moraleda:Sandoz: Consultancy, Other: Travel Expenses; Novartis: Consultancy, Other: Travel Expenses; Gilead: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Research Funding; Takeda: Consultancy, Other: Travel Expenses. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Diaz-Ricart:German Jose Carreras Leukaemia Foundation: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding.

Sixty female dairy calves (body weight, BW, 43·2±0·58 kg and age 9·8±0·61 d) were arranged in two groups to compare the short-term and long-term effects of an enhanced-growth feeding programme (EF) with those of a conventional-growth feeding programme (CF). After 1 week of adaptation to a milk replacer (MR), CF calves were fed 4 l/d of MR (25% crude protein, CP; 19·2% ether extract) at 12% dry matter (DM) from days 1 to 27 and 2 l/d at 12% DM from days 28 to 34, and the EF calves were offered the same MR at 18% DM: 4 l/d from days 1 to 6, 6 l/d from days 7 to 13, 7 l/d from days 14 to 20, 6 l/d from days 21 to 27 and 3 l/d from day 28 to weaning at day 34 of the study (50 d of age). Individual calf starter (20·7% CP) intake was recorded daily from the beginning until day 41 of study (57 d of age). Then, calves were placed in groups of six and they received a total mixed ration (TMR) containing 18·5% CP until day 56 d of study (72 d of age). Then, heifers were moved to larger pens and were fed the same TMR in both treatments at each subsequent stage of growth throughout the study. Calves were weighed weekly until day 56 of study and before every pen change (days 94, 149, 200, 387 of study). When heifers were 400 d old and weighed >380 kg, they were moved to a breeding pen where oestruses were checked three times a day. Heifers were inseminated 12 h after the detection of oestrus. One month before calving, heifers were returned to their original farm and milk yield at 305 days in milk was recorded from 28 cows. Starter intake was greater (P<0·001) in CF than in EF calves (0·79 v. 0·29±0·043 kg/d, respectively) during the preweaning period, but TMR consumption was similar in both treatments from days 42 to 56 of study. BW of EF calves was greater (P<0·01) than that of CF calves at weaning (76·4 v. 71·6±1·10 kg, respectively), but BW was not different at day 387 of study (405 d of age) (406·3 v. 401·3±4·05 kg, respectively). There were numerical differences in age at first breeding, fertility at first artificial insemination, age at pregnancy, and milk yield but some of these differences might have reached statistical significance with more replication.

Abstract Mitochondria (mt) provide cells energy through oxidative phosphorylation (OXPHOS), regulate cell survival and death, and likely affect innate and adaptive immune system responses. Polymorphisms in mtDNA can be grouped into haplotypes (mthaps) that are associated with human global migration. Experiments using cybrids (identical cell clones that differ in mthaps) show differences in OXPHOS, reactive oxygen species generation and immune recognition. Numerous association studies have linked specific mthaps to disease occurrence, severity and/or therapy response. Since HCT is a period of high metabolic demand, we explored whether patient or donor mthaps are associated with HCT outcomes. Pre-transplant DNA was available from 437 adult and pediatric patients (6 months-69.6 years) who received an allogeneic transplant at the University of Minnesota for a hematological malignancy between 1995 and 2005, along with DNA from 327 donors. Of the HCTs, 213 were related donor (198 siblings, 15 other), 73 unrelated and 151 umbilical cord blood. Clinical and laboratory data were collected on all patients. Patient and donor DNA were genotyped for 11 common European mthaps (most to least common: H, J, U, T, Z, K, V, X, I, W, K2); 29 samples did not correspond with one of the 11 mtHaps and were labeled as ‘other’. Three separate analyses were performed: 1) sibling transplant outcomes (matched for mthap), 2) related and unrelated transplant outcomes based on patient mthap, and 3) related and unrelated transplant outcomes based on donor mthap. Multivariate models (adjusted for stem cell source, disease risk, conditioning regimen, patient CMV serostatus and patient sex as appropriate) were used to calculate relative risks (RR) and 95% confidence intervals (CI) comparing HCT outcomes to the most common haplotype (H). More than 80% of the 11 mthaps occurred in non-Hispanic whites, although 47% of Z (7/15 patients) were of other race/ethnicity. Among matched siblings, mthap did not differ with HLA mismatch (p=0.59). Compared to mthap H (43 events/83 patients, 52%), recipient siblings with I (5/6) and V (5/5) were significantly more likely to die within 5 years (RR=3.0, 95%CI 1.2-7.9, p=0.02; 4.6, 1.8-12.3, p<0.01, respectively). Patients with W (3/4) experienced significantly higher aGVHD II-IV events (RR=2.1; 1.1-2.4, p=0.03) than H (32/83, 39%), while K2 (0/4), K (1/8) and J (4/21) experienced no or fewer events. For aGVHD III-IV, patients with U (5/19) and V (2/5) experienced significantly higher events than H (9/83, 11%); there were no events for K and K2. Similar results were observed when considering outcomes for all recipients: compared to H (78/156, 57%), fewer aGVHD II-IV events were observed for J (17/59) and K (6/22) patients (0.5, 0.3-0.8, p<0.01; 0.4, 0.2-0.9, p=0.03, respectively). Lastly, when comparing donors relative to H (68/127, 54%), 6/7 recipients with I donors died within 5 years post HCT (2.7, 1.2-6.2, p=0.02), while only 1/7 and 1/4 patients receiving a transplant from a K2 or W donor, respectively, died. Further, compared to H donors (27/127, 23%), no patients who received a HCT from a K2 donor relapsed and only 4/34 patients from U donors relapsed. Ours is the first study to demonstrate that mthaps may be an important consideration in determining patient outcomes following HCT. Given interest in mthaps in disease susceptibility, we will conduct functional studies to better understand the role of patient and donor mthaps in OXPHOS and immune system responses in the presence of HCT. These preliminary results need confirmation in larger studies. If validated, it would be feasible to select donor mthaps associated with less GVHD and/or relapse (e.g., J, K2, U) or avoid use of donor mthaps associated with adverse outcomes (e.g., I,V). Disclosures No relevant conflicts of interest to declare.

Abstract Background and Methods MDS are complex conditions, described with sometimes confusing terminology (e.g., “refractory anemia”), and contemporary drug therapies (tx) for MDS require repeated administration cycles to achieve clinical effect. Lack of disease understanding or premature tx discontinuation may result in poorer outcomes for patients (pts). To better understand physician (MD) and pt perceptions about MDS and tx decisions, we conducted two online surveys: one for pts with MDS and one for healthcare providers (HCP) registered with the non-profit Aplastic Anemia & MDS International Foundation. The protocol and consent were approved by a central Institutional Review Board. Pt and HCP surveys consisted of 57 and 49 questions, respectively, and assessed understanding of MDS, perceptions of specific tx, barriers to tx adherence, and overall tx experience. Data were analyzed using proportions, means, and medians; groups were compared using a Chi-squared test. Results Of 4,039 pts invited to participate via e-mail, 477 (12%) complete responses were received from 42 US States. Of responders, 247 (52%) were men; 63% were ≥age 60; pts were diagnosed with MDS a median of 5 years prior to the survey (range, 0-32 years). Of 4,594 HCPs invited to participate, 120 (3%) complete responses were received. Due to low participation among other HCP groups, only MD responses were examined. Of the 61 MDs (from 23 US states), 35 (57%) practice in an academic setting and 26 (43%) in the community setting. Survey responses from self-designated academic and community MDs did not differ significantly. Among MDs, 48% reported they see 5-19 new MDS pts per year. Only 10% of pts reported MDS was described to them as “cancer”, compared to how 59% of MDs stated they described it (p<.001). Only 29% of pts reported that MDS is “curable”, compared to 52% of MDs (p<.001). Forty-two percent of pts had received at least one disease-modifying tx: azacitidine (AZA, 58%), decitabine (DAC, 27%), lenalidomide (LEN, 35%) or hematopoetic stem cell transplant (HSCT, 26%) (total >100% due to multiple answers). MD and pt perceptions of active tx were significantly different, with MDs overestimating quality of life (QOL) benefits and underestimating the burden of tx on pt activities. [Table 1] MDs interpreted the benefit of active tx significantly higher than pts, however pts perceived the actual tx experience more positively than MDs. [Table 2] Most pts (81%) reported that MDs had the most influence on their tx decisions. Sixty-nine percent of MDs reported recommending stopping tx prior to the completion of tx regimen. Reported reasons diverged between pts and MDs, including burden of tx exceeding the benefit to the pt, as well as perceptions that the impact on the pt and family was too great. [Table 3] Conclusion Physicians and pts with MDS have distinct views of the value of tx for MDS, with MDs underestimating the impact of tx on pt QOL while overestimating it as justification for stopping tx. Improved communication may improve understanding of disease and impact of active treatment and achieve better tx adeherence and responses. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 4949 Background and Methods: Previous studies have suggested that many patients (pts) with MDS have incomplete understanding of their disease and its treatment. In addition, contemporary drug therapies (tx) for MDS often require repeated treatment administration cycles to achieve clinical effect, and premature discontinuation or incomplete adherence may result in lack of benefit in pts who might have responded to a longer course of tx. In order to better understand physician and pt perceptions about MDS and decisions about continuing tx, we conducted two online surveys in February 2012: one for pts with MDS and one for healthcare providers (HCP) registered with the Aplastic Anemia & MDS International Foundation. A $50 Amazon gift card was offered to the first 200 respondents in each group; acceptance constituted consent. The protocol was approved by a central Institutional Review Board. Pt and HCP surveys consisted of 57 and 49 questions, respectively, assessing understanding of MDS, perceptions of specific tx, perceived barriers to tx adherence, and overall tx experience. Data were analyzed using proportions, means and medians, and comparisons between groups were calculated using Pearson's Chi square where appropriate. Results: 477 complete pt responses were received from 42 US States, as well as 120 complete HCP responses. Of pt responders, 247 (52%) were men, 63% were ≥60 years old, and the median time from MDS diagnosis was 5 years (range, 0–32 years). Because of low participation among other HCP groups, only physician (MD) responses are analyzed here. Of the 61 physicians (from 23 US states), 35 (57%) practice in an academic setting and 26 (43%) in the community setting; 48% reported they see 5–19 new MDS pts per year. Survey responses from academic and community physicians did not differ significantly. Only 10% of pts reported agreement that MDS is a “cancer”, compared to 59% of physicians (p<. 001). Only 29% of pts report that MDS is a “curable” condition, compared to 52% of physicians (p<. 001). Forty-two percent of patients had received at least one active tx: azacitidine (AZA, 58%), decitabine (DAC, 27%), lenalidomide (LEN, 35%) or hematopoetic stem cell transplant (HSCT, 26%) (total >100% due to multiple answers). Physicians and pt perceptions of specific active tx were significantly different, especially regarding quality of life (QOL), adverse events and impact of tx on pt activities. [Table 1]. Physicians viewed the potential benefits of active tx significantly greater than did pts, however pts perceived the actual tx experience more positively than doctors. [Table 2] Sixty-nine percent of physicians reported recommending stopping tx prior to the completion of a planned tx course, most commonly due to adverse events and the burden of therapy outweighing benefit. [Table 3] Conclusion: Physicians and pts with MDS have disparate views of MDS characteristics and the value and limitations of tx for MDS. Improved communication and education may increase understanding of disease and achieve better results, including greater treatment adherence. Disclosures: Huber: Celgene: Research Funding, This study was funded by an unrestricted grant from Celgene to the AA&MDS IF. Other. Dennison:Celgene: Research Funding.

Abstract Abstract 861 Background: Omacetaxine is a first-in-class cetaxine with clinical activity against Ph+ CML and a mechanism of action independent of tyrosine kinase inhibition. The development of TKI resistance and intolerance is an emerging problem and patients (Pts) who have failed multiple TKIs may benefit from an alternative therapy for CML. Study Goals: To evaluate the safety and efficacy of SC omacetaxine in CML Pts who are resistant and/or intolerant to two or more TKIs. Methods: Eligible Pts included adult CML Pts in chronic, accelerated, or blast disease phase (CP, AP, BP) with resistance and/or intolerance to at least two TKIs. Bcr-Abl mutational analysis was performed at one of 2 central reference laboratories and Pts harboring the T315I Bcr-Abl mutation were enrolled in a separate clinical trial. Induction schedule: 1.25 mg/m2 SC omacetaxine twice daily for 14 days every 28 days until hematologic response. Maintenance dosing: 1.25 mg/m2 SC omacetaxine twice daily for 7 days every 28 days. Study Results: To date, 99 Pts have enrolled, with data available for analysis on 65 Pts (30 CP, 20 AP and 15 BP). The median age was 57 yrs (23-78) with 52% male and a median disease duration of 77 mo (1-197). Nearly all (64/65, 99%) Pts failed prior IM therapy and 57% failed 3 or more prior TKIs. Baseline mutations were identified in 21 (32%) Pts with 10 non-P Loop, 7 P Loop and 4 compound mutations. Baseline clonal evolution was evident in 5 (17%) CP, 8 (40%) AP, and 13 (87%) BP Pts. Six CP Pts entered the study in CHR. The median follow-up for all Pts is 4.0 mo (0.3 to 14.7). Efficacy: In CP Pts, CHR was achieved in 18 Pts and maintained for more than 8 weeks in the 6 Pts enrolled with baseline CHR, for an overall CHR rate of 80%; median duration 4.7+ mo (1.4 to 13). Major cytogenetic response (MCyR) was achieved in 6 (20%) CP Pts (1 complete, 5 partial); median duration 1.6+ mo (0.0 to 2.9). Major molecular response was achieved in 10% of CP Pts. In AP Pts, overall hematologic response was achieved in 15 (75%) Pts; 12 CHR and 3 return to chronic phase (RCP); median duration 2.5+ mo (1.8 to 10.5). One (5%) AP Pt achieved a complete CyR, identified immediately prior to data cut-off and ongoing. In BP Pts, overall hematologic response was achieved in 8 (53.3%); 6 CHR and 2 RCP. Three Pts (2 CP, 1 AP) received bone marrow/stem cell transplants after achieving major cytogenetic response, a therapeutic option not available to them at study enrollment. No deaths occurred in CP Pts. The median overall survival for AP Pts has not been reached and 13 Pts were alive at the time of data cut-off. Median overall survival was 14.5 mo for BP Pts. Median time to progression was 11.1, 5.7, and 2.6 mo for CP, AP, and BP Pts, respectively. Safety: Grade 3/4 related events occurred in 47/65 (72%) of Pts. The most commonly reported events (>15%) were thrombocytopenia (43%), neutropenia (29%), and anemia (22%). Non-hematologic toxicities were generally grade 1/2 with the most frequently reported; diarrhea (32%), nausea (26%), pyrexia (23%), headache (20%), fatigue (19%), vomiting (17%), and asthenia (17%). Grade 3/4 non-hematologic toxicities were uncommon with no events occurring in >5% of Pts and fatigue (3%) the most common event. Treatment delays occurred in approximately 50% of the Pts with median duration of approximately 9 days for all disease phases and cycles (CP=7, AP=11, and BP=12 days). The primary causes of delay were thrombocytopenia, neutropenia and pancytopenia. Deaths occurred in 6 (9.2%) Pts, including 2 (10%) AP pts and 4 (26.7%) BP Pts. Of the deaths, one occurrence in an AP Pt was considered to be possibly related to omacetaxine treatment (febrile neutropenia). Conclusions: Omacetaxine administered by SC injection produced hematologic and cytogenetic responses with a safety profile primarily consisting of hematologic toxicities. This study demonstrated that omacetaxine may be a potential treatment option for CML Pts who have failed multiple TKIs. Disclosures: Cortes-Franco: ChemGenex: Membership on an entity's Board of Directors or advisory committees, Research Funding. Raghunadharao:ChemGenex: Research Funding. Parikh:ChemGenex: Research Funding. Wetzler:ChemGenex: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lipton:ChemGenex: Membership on an entity's Board of Directors or advisory committees, Research Funding. Jones:ChemGenex: Research Funding. Hochhaus:ChemGenex: Research Funding. Kantarjian:ChemGenex: Membership on an entity's Board of Directors or advisory committees, Research Funding. Craig:ChemGenex: Employment. Benichou:ChemGenex: Employment. Humphriss:ChemGenex: Employment. Nicolini:ChemGenex: Research Funding.

Abstract Background and objective. Inotuzumab ozogamicin (InO) was approved for patients (pts) with relapsed/refractory (R/R) CD22-positive acute lymphoblastic leukemia (ALL) based on the results of INO-VATE trial (Kantarjian et al, 2016). There are scarce studies evaluating the results of InO therapy in real life in similar pts as those from the INO-VATE trial. Our objective was to analyze the outcomes of pts included in the compassionate program of InO in Spain (June 2013-April 2018) before definitive approval. Patients and Methods. Inclusion criteria were age &gt;18 yrs., CD22+ ALL, R/R resistant to ≥2 previous lines, Ph+ ALL resistant/intolerant to TKI, ECOG ≤2 or &gt;2 if due to ALL, Bilirubin &lt;1.5 ULN, AST & ALT &lt;2.5 ULN, Creatinine ≤ 1.5 ULN. Exclusion criteria included mature B ALL, active CNS leukemia, chemotherapy in the two previous weeks, HSCT in the previous 6 months, grade ≥2 aGVHD or cGVHD, acute or chronic hepatitis B or C, HIV infection, VOD/SOS and antecedent chronic liver disease. Cycles of InO (0.8 mg/m 2 IV d1, and 0.5mg/m 2 IV on d8 and d15) were given every 21 days. Main outcomes: early death, CR/CRi, CR duration, PFS, OS and HSCT realization after InO. Results. 34 pts were included in the trial, 21 males, median age 43 yrs (range 19-73), ECOG &lt;2 22/26, WBC count 7.8 x10 9/L (0.3-388), pro B ALL 4/33, common 26/33, pre-B 3/33, Ph+ ALL 5/34 (15%), BM blast cells &gt;50% 15/33 (45%). 25/34 (73%) of pts received &gt;2 previous lines of therapy and 20 (59%) were previously transplanted. The duration of first CR remission before InO was &lt;12 months in 16/33 pts (49%) and 16/34 pts were refractory to the last treatment before InO. The median number of InO cycles was 2 (1-6). One pt withdrew the study before evaluation, 5 (15%) dead during therapy and 21 (64%) achieved CR/CRi. Ten pts (29%) were transplanted. With a median follow-up for alive patients after InO start of 26 months, the medians (95%CI) of DR, PFS and OS were 4.7 months (2.4-7.0), 3.5 (2.0-5.0) and 4.0 months (1.9-6.1), respectively. CR duration, PFS and OS were significantly shorter in refractory ALL (Figure 1A), pts with first CR (CR1) duration &lt;12 months (Figure 1B) and in those without previous HSCT. The number of previous lines of therapy did not show impact on outcome. The most frequent adverse events were hepatic (24%), infectious (18%), hematologic (15%) and gastrointestinal (9%). 3/10 transplanted patients showed grade 3-4 VOD/SOS. Grade 5 toxic events were hepatic (n=2), infection (n=2) and hemorrhage (n=1). Conclusion. The results in this series of compassionate use of InO for R/R ALL before approval for clinical use were slightly inferior to that of the INO-VATE trial. However, patients form this series had poorer risk factors than those included in that trial. The frequency and type of AE were similar to that of observed in the INO-VATE trial. Supported in part by grant 2017 SGR288 (GRC) Generalitat de Catalunya and "La Caixa" Foundation. Figure 1. Overall survival according to ALL status at inotuzumab start (A) and to duration of first complete remission (B) Figure 1 Figure 1. Disclosures Ribera: AMGEN: Consultancy, Research Funding, Speakers Bureau; SHIRE: Consultancy, Speakers Bureau; ARIAD: Consultancy, Research Funding, Speakers Bureau; TAKEDA: Consultancy, Research Funding, Speakers Bureau; NOVARTIS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau. Hernández-Rivas: Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract Rational: Patients with t-AML are those previously treated for primary malignancy and are categorized with poor prognosis. t-AML treatment options include intensive chemotherapy (IC), hypomethylating agents (HMA) or low dose cytarabine (LDC). However, survival remains poor and allogeneic hematopoietic cell transplantation (Allo-HCT) could lead to better outcomes. The aim of this analysis is to assess the outcome of all consecutive t-AML pts from two regional centers in France, based on treatment intensity, and to identify prognostic factors. Patients and Methods: between January 2006 and December 2019, 112 adult pts diagnosed with t-AML occurring after treatment of solid tumors (ST; n=72), hematologic malignancies (HM; n=34) or autoimmune diseases (AID; n=6). Pts received chemotherapy and/or radiotherapy or high dose chemotherapy followed by autologous hematopoietic cell transplantation (Auto-HCT) in some. All eligible t-AML pts received intensive chemotherapy (IC, n=55) with the combination of anthracycline and cytarabine in 48 pts and CPX-351 in 7 pts. Unfit pts received non-IC (9 LDC, 24 HMA). The third study group (24 pts) received best supportive care (BSC). Fifteen pts underwent HSCT in first CR. Statistical analysis: We performed a descriptive analysis of the baseline characteristics and each treatment group was compared with a Kruskal-Wallis test and a Pearson's Chi-square test. Survival curves (Kaplan-Meier method) were compared with a log-rank test. Univariate and multivariate analyses on survival, relapse and NRM were done using Cox regression, Gray test, Fine & Gray regression. The bilateral level of significance was set at 5%. All analyses and graphics were made under the R program (v3.5.1). A pair-matched control analysis with de novo AML was performed only on pts who received IC matched for age, cytogenetics and ELN 2010 classification. Results: A total of 112 t-AML pts were identified, 56 were males (50%) with a median age of 68 yrs (19-87) at t-AML diagnosis. Before t-AML, 72 pts had ST (64.5%), 34 HM (30.5%) and 6 AID (5%). Forty-six pts (41%) received chemotherapy alone for their primary cancer, 17 (15%) radiotherapy alone, 49 (44%) radio chemotherapy, 17 (15%) auto-HCT and 6 (5%) long-term methotrexate for AID. Median interval from treatment of previous ST or HM to t-AML diagnosis was 4.7 years in ST, 6.6 years in HM and 21 years in AID (p=0.03). At t-AML diagnosis, 42% of pts presented an unfavorable karyotype and 44% an unfavorable ELN 2010 classification. Regarding molecular alterations, FLT3-ITD, FLT3-TKD, NPM1 and IDH1/2 mutations were observed in 6.9, 2.3, 11.5 and 2.3% of pts respectively. MECOM1 was overexpressed in 25.5% of cases. Among treated pts (n=88), 43 pts (49%) achieved CR: 4 from 33 (12%) in non-IC pts (3 in HMA and 1 in LDC) and 39 from 55 (71%) in IC pts. Fifteen pts (17%) underwent Allo-HCT with a median interval between AML diagnosis and Allo-HCT of 4.7 mo (2.6-17.5). The best response after transplantation was CR in 10 pts; at the last follow up, 4 pts are alive (3 in CR and 1 in relapse) and 11 died (5 from relapse, 5 from TRM causes and 1 from another subsequent malignancy). Overall, with a median follow up of 5.5 mo (0-144), the median OS and DFS were 9 mo (5.9-13.5) and 6.3 mo (5.3-10.3) respectively (Figure). There was a significant difference between the 3 treatment groups concerning OS (p&lt;0.001) and DFS (p&lt;0.001) with a significant difference in OS between IC and non-IC groups (p=0.02). In the 88 treated t-AML pts, with a median follow up of 8.2 mo (0.3-144), the median OS was 13.5 mo (10.3-19.6) and the median DFS was 8.2 mo (7-13.7). Multivariate analysis for total and treated populations showed no impact of all variables related to previous malignancies except for auto-HCT pre-t-AML (significant negative impact on OS, DFS, NRM), WBC at t-AML diagnosis (negative impact on OS, DFS) and chemotherapy (positive in total population on OS, DFS, NRM and negative impact of IC on OS and NRM in treated pts) . In IC treated pts, we showed, in a pair-matched analysis with de novo AML, no difference in term of OS and DFS due to a significant higher CI of NRM (p=0.045) at 24 mo (40% in t-AML versus 27.4% for de novo AML) and a lower CI of relapse (NS) at 24 mo (33% in t-AML versus 47.6% for de novo AML). Conclusion: The prognosis of t-AML remains poor and our study showed the advantage of using intensive chemotherapy whenever possible and, in comparison with de-novo AML, a higher NRM and a lower incidence relapse. Figure 1 Figure 1. Disclosures Nicolini: Sun Pharma Ltd.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kartos Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations, expenses, Research Funding; Incyte Biosciences: Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau; BMS: Honoraria.

Background: Optimal treatment for medically less fit adults with acute myeloid leukemia (AML) remains uncertain. Retrospective data suggest intensive therapy may lead to better outcomes in these patients. However, these findings must be interpreted cautiously because of the possibility of selection bias and other confounders. Ideally, the optimal treatment intensity is defined via randomized trial but whether patients and their physicians are amenable to such a study is unknown. We therefore designed a trial (NCT03012672) to 1) evaluate the feasibility of randomization between intensive and non-intensive therapy in this population and 2) examine the impact of treatment intensity on response rate and survival. We used CLAG-M as high-dose cytarabine-based intensive induction therapy. Rather than selecting different classes of drugs in the 2 treatment arms- which may have different modes of action and therefore confound the question of treatment intensity - we used reduced-dose ("mini") CLAG-M as the non-intensive comparator. Methods: Adults ≥18 years were eligible if they had untreated AML or high-grade myeloid neoplasms (≥10% blasts in blood or marrow) and were medically less fit as defined by having a "treatment related mortality" (TRM) score of ≥13.1, corresponding to a &gt;10-15% 28-day mortality with intensive chemotherapy. Left ventricular ejection fraction ≤45% was the only organ function exclusion. Patient-physician pairs were first asked if they were amenable to randomized treatment allocation. If so, they were randomized 1:1 to mini- vs. regular-dose CLAG-M. If not, in order to evaluate our secondary endpoints, the patient or physician could choose the treatment arm and still enroll on study. Patients and physicians then completed surveys elucidating their decision-making processes. Up to 2 induction courses were given with mini- vs. regular-dose CLAG-M: cladribine 2 or 5 mg/m2/day (days 1-5), cytarabine 100 or 2,000 mg/m2/day (days 1-5), G-CSF 300 or 480µcg/day for weight &lt;/≥76kg in both arms (days 0-5), and mitoxantrone 6 or 18 mg/m2/day (days 1-3). CLAG at identical doses was used for post-remission therapy for up to 4 (regular-dose CLAG) or 12 (mini-CLAG) cycles. The primary endpoint was feasibility of randomization, defined as ≥26/50 of patient-physician pairs agreeing to randomization. Secondary outcomes included rate of complete remission (CR) negative for measurable ("minimal") residual disease (MRD), rate of CR plus CR with incomplete hematologic recovery (CR+CRi), and overall survival (OS). Results: This trial enrolled 33 patients. Only 3 (9%) patient/physician pairs agreed to randomization and thus randomization was deemed infeasible (primary endpoint). Eighteen pairs chose mini-CLAG-M and 12 regular-dose CLAG-M for a total of 19 subjects in the lower dose and 14 subjects in the higher dose arms. The decision favoring lower dose treatment was made largely by the physician in 5/18 (28%) cases, the patient in 11/18 (61%) cases and both in 2/18 (11%). The decision favoring the higher dose arm was made by the patient in most cases 9/12 (75%), both physician and patient in 2/12 (16%) and the physician in only 1/12 (8%) cases. Despite the limitations of lack of randomization, patients' baseline characteristics were well balanced with regard to age, performance status, TRM score, lab values and cytogenetic/mutational risk categories (Table 1). One patient was not yet evaluable for response or TRM at data cutoff. Rates of MRDneg CR were comparable: 6/19 (32%) in the lower and 3/14 (21%) in the higher dose groups (p=0.70). CR+CRi rates were also similar in both arms (43% vs. 56% in lower vs. higher dose arms; p=0.47). Three (16%) patients experienced early death in the lower dose arm vs. 1 (7%) in the higher dose arm (p=0.43). With a median follow up of 4.2 months, there was no survival difference between the two groups (median OS of 6.1 months in the lower vs. 4.7 months in the higher dose arm; p=0.81; Figure 1). Conclusions: Randomization of medically unfit patients to lower- vs. higher-intensity therapy was not feasible, and physicians rarely chose higher intensity therapy in this patient group. Acknowledging the limitation of short follow-up time and small sample size, our trial did not identify significant differences in outcomes between intensive and non-intensive chemotherapy. Analysis of differences in QOL and healthcare resource utilization between groups is ongoing. Disclosures Halpern: Pfizer Pharmaceuticals: Research Funding; Bayer Pharmaceuticals: Research Funding. Othus:Celgene: Other: Data Safety and Monitoring Committee. Gardner:Abbvie: Speakers Bureau. Percival:Genentech: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc.: Research Funding; Nohla Therapeutics: Research Funding. Scott:Incyte: Consultancy; Novartis: Consultancy; Agios: Consultancy; Celgene: Consultancy. Becker:AbbVie, Amgen, Bristol-Myers Squibb, Glycomimetics, Invivoscribe, JW Pharmaceuticals, Novartis, Trovagene: Research Funding; Accordant Health Services/Caremark: Consultancy; The France Foundation: Honoraria. Oehler:Pfizer Inc.: Research Funding; Blueprint Medicines: Consultancy. Walter:BioLineRx: Consultancy; Astellas: Consultancy; Argenx BVBA: Consultancy; BiVictriX: Consultancy; Agios: Consultancy; Amgen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Boehringer Ingelheim: Consultancy; Boston Biomedical: Consultancy; Covagen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Seattle Genetics: Research Funding; Race Oncology: Consultancy; Aptevo Therapeutics: Consultancy, Research Funding; Kite Pharma: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding. OffLabel Disclosure: Cladribine is FDA-approved for Hairy Cell Leukemia. Here we describe its use for AML, where is is also widely used with prior publications supporting its use

Abstract Background: Acute T-cell lymphoblastic leukemia (T-ALL)/ lymphoma (T-LBL) are immature T-cell malignancies with very poor outcomes. In patients with relapsed disease, survival is often < 12 months (Marks et al, Blood, 2009). Prognostic correlates and treatment outcomes after relapse remain largely unknown. Aims: To evaluate prognostic correlates and treatment outcomes in patients with relapsed T-ALL/LBL. Methods: After IRB approval, 92 consecutive patients with T-cell ALL/LBL were identified. 41 patients with relapsed disease after achieving a first complete remission (CR1) were included in the study group. Features at the time of relapse were retrospectively abstracted and analyzed. Survival time after relapse was calculated from the time of relapse until death or last follow-up. Conventional methods were used for statistical analysis. Results: A. Baseline characteristics of all patients 92 patients were identified [41 LBL, 51 ALL]. Median age was 33 years (range; 18-88) and 66 (72%) were males. Median follow-up was 25 months (range 0.9-260). 13(14%) received palliative care or were lost to follow-up before treatment initiation. At last follow-up, there were 41 (52%, n = 79) relapses and 42 (46%, n = 92) deaths. Of 79 patients, 71 (90%) achieved a CR1 and 8 (10%) had primary refractory disease. Comparisons between ALL and LBL revealed expected differences in presenting features such as frequency of primary mediastinal mass at presentation in LBL and high leukocyte count in ALL. Significant differences in treatment were seen. Asparaginase-based and ALL-directed therapy were more common in the ALL group (71% vs. 45%, p = 0.009; 88% vs. 71%, p = 0.04). 13 (81%) LBL and 14 (27%) ALL underwent allogeneic SCT. The remaining three in each group underwent autologous SCT in CR1. B. Characteristics of relapsed patients 41 relapsed after achieving CR1 [23 LBL, 18 ALL]. Median time to relapse was 8.0 months (range 2.3-130), with no difference between ALL and LBL groups. Median age was 34 years (range 19-71) and 29 (71%) were males. Median follow-up after relapse was 7.2 months (range 0.3-207). At time of last follow-up, there were 30 (73%) deaths, 25 (61%) achieved a second complete remission (CR2) and 14 (34%) had persistent disease. 12 (48%) had relapse following CR2. 34 (83%) relapsed following CR1 after induction chemotherapy alone. 6 (15%) and 1 (2%) relapsed following allogeneic and autologous SCT respectively. 27 (66%) had BM involvement, 5 (12%) had CNS involvement, 13 (32%) had mediastinal involvement, and 3 (7%) had isolated extramedullary relapse. Ten (43%) patients with LBL relapsed with ALL. Of 27 patients with available data, 9 (33%) had high-risk cytogenetics at relapse, defined as ≥ 5 chromosomal abnormalities and/or markers known to confer an unfavorable prognosis. 16 of these 27 patients had follow-up cytogenetic studies performed, of which 8 (50%) had evidence of clonal evolution. Patients were treated with up to five regimens. 12 (31%) received asparaginase-based therapy and 13 (33%) received nelarabine with CR2 rates of 75% and 25% respectively. Median number of regimens needed to achieve CR2 was one. 18 (46%) went onto SCT following CR2: 14 (allogeneic), 3 (autologous), and 1 (donor lymphocyte infusion). The majority received myeloablative conditioning (92%). C. Outcomes and prognostic correlates for survival after relapse Median survival following relapse was 8.2 months (IQR 4.1-21.3) and did not differ between LBL and ALL. Nine (36%) who achieved CR2 are alive at time of last follow-up. 25 (61%) achieved CR2, but 12 (48%) relapsed following CR2, with median time to second relapse of 7.6 months (IQR 4.7-14). Nine of 18 who underwent SCT following CR2 had disease relapse (8 allogeneic, 1 autologous). Only BM involvement at relapse significantly correlated with post-relapse survival (HR 2.4 [1.1, 5.1], p = 0.03). Clonal evolution, high-risk cytogenetics, nelarabine therapy, achieving CR2, and SCT were not independent predictors of survival in our small subset of patients. Conclusion: Patients with relapsed T-ALL/LBL have dismal outcomes, in spite of advances in therapy with newer agents such as nelarabine and the use of allogeneic SCT. Regardless of T-ALL/LBL subtype, BM involvement at relapse appears to be a significant factor negatively impacting post-relapse survival. Further studies are needed to validate these findings. Disclosures Al-Kali: Celgene: Research Funding. Thompson:Kite Pharma: Research Funding.

Introduction: The most common cause of treatment failure after allogeneic hematopoetic stem cell transplantation (aHSCT) is relapse. The combination of venetoclax and the hypomethylating agents (HMA) azacitidine (AZA) or decitabine (DAC) have shown promising efficacy in elderly patients with AML. We here present clinical data on 32 patients, who were treated with an HMA/venetoclax combination therapy (HMAClax) for relapse of a myeloid malignancy after aHSCT, collected retrospectively from 11 German centers. Results: Sixteen patients (50%) were male, median age was 54 years (30.8-71.5). Diagnoses at aHSCT were 25 AML (17 primary, 8 emerging from MDS, CMML or OMF), 5 MDS, 1 CMML and one atypical CML. Twenty six patients were treated for relapse after their 1st and 6 after their 2nd aHSCT. Only 9 patients were in CR at aHSCT. The majority received a graft of a matched unrelated donor (21), 4 from an HLA-identical sibling and 7 from a haploidentical relative. Conditioning was myeloablative in 15 and RIC in 17patients. Median time from aHSCT to last relapse was 5.7ms (1.1-67.8). Five patients had molecular (MR) and 23 had hematologic relapses (HR), 4 patients had extramedullary manifestations 3 with concurrent HR and 1 with MR. Twenty-one patients were treated for 1st and 5 for 2nd relapse after 1st aHSCT. Four patients were treated for 1st and 2 for 2nd relapse after 2nd aHSCT. HMAClax was first line therapy for relapse in 8, 2nd line in 22, 3rd line 1 and 4th line in 1 patient. In 21 patients relapse had been refractory to HMA (+/- DLI, +/- lenalidomide). Median time from relapse to HMAClax was 1.8 ms (0.3-42.9). Twelve patients received AZA and 19 DAC with venetoclax. One patient was switched from AZAClax to DAClax because of rising MRD after 6 cycles and back to AZAClax after another 7 cycles. Six patients received DLI. Median number of cycles was 2 (1-15). Six patients are still on therapy. In total 75 cycles were given. Three patients had non-fatal tumor lysis syndrome. All but one patient had grade 3/4 neutropenia and 25 patients (78%) had grade 3/4 thrombocytopenia. Hospital admission for grade 3/4 infections was necessary in 23 patients (72%), 5 of these infections (22%) were fatal. Overall response rate was 43% (12/28, 2 CR MRD-, 4 CR, 2 CRi, 3 PR, 1 MLFS). Two patients died of infection before first response evaluation and in another 2 response has not been evaluated yet. ORR for patients who received first line HMAClax was 80% (4/5) and 35% (8/23) for salvage treatment. Three of 5 patients with MR reached CR, 2 received HMAClax first line. Time to best response was 1.2ms (0.7-3.8). Six patients lost best response after 1ms (0.4-3.3.) 2 underwent second transplant in remission, 4 have ongoing responses (0.4, 0.7, 3.1 and 8.8ms at last follow up). On July 25th 2019, median follow up was 3.3 ms (0.9-17.3), 20 patients (63%) had died and 12 were alive. Six were continuing HMAClax. One patient developed cGvHD and 4 underwent second aHSCT (2 in remission). Estimated median overall survival was 3.7ms (CI 2.9-4.7). Four responders are continuing treatment with HMAClax. Patients, who responded had an estimated OS of 11.1ms (2 underwent second aHSCT in remission). Median survival of patients with HMAClax first line therapy was 5.8ms and of patients with HMAClax salvage therapy 3.7ms. Conclusion: For patients relapsing after aHSCT, venetoclax plus AZA or DAC seems to be an effective, but also highly hematotoxic therapy. Responses occurred fast and were more frequently seen during 1st line treatment for relapse. Duration of response was short, especially in patients receiving HMAClax as 2nd, 3rd or 4th line therapy. Therefore HMAClax should be explored as 1st line therapy for relapse after aHSCT in combination with DLI or as a bridge to 2nd transplant. Disclosures Schuler: Celgene: Other: travel grants; Novartis: Honoraria, Other: travel grants; Alexion: Other: travel grants. Bug:Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Hexal: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Other: travel grants; Celgene Neovii: Other: travel grant. Crysandt:Incyte: Membership on an entity's Board of Directors or advisory committees; Amgem: Other: travel grant; celgene: Other: travel grant; Pfizer: Other: travel grant; Gilead: Other: travel grant. Jost:Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Gilead: Other: travel grants; Daiichi: Honoraria. Kaivers:Jazz Pharmaceuticals: Other: Travel Support. Mueller:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; CTI Life Sciences: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Financing of Scientific Research; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Gentium: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Jazz: Honoraria; Pharmaceuticals: Honoraria; Neovii: Honoraria; Novartis: Honoraria; Sanofi: Honoraria. Rautenberg:Jazz Pharmaceuticals: Other: Travel Support; Celgene: Honoraria, Other: Travel Support. Wolff:Takeda: Honoraria; Mallinckrodt: Honoraria; Novartis: Honoraria; Neovi: Honoraria. Schroeder:Celgene Corporation: Consultancy, Honoraria, Research Funding. Off Label Use: Venetoclax was used in combination with azacitidine or decitabine. The combination is not approved in the EU so far.. Kobbe:Pfizer: Honoraria, Other: Travel support; Abbvie: Honoraria, Other: Travel support; Biotest: Honoraria, Other: Travel support; Roche: Honoraria, Other: Travel support; Jazz: Honoraria, Other: Travel support; MSD: Honoraria, Other: Travel support; Celgene: Honoraria, Other: Travel support, Research Funding; Takeda: Honoraria, Other: Travel support; Amgen: Honoraria, Other: Travel support, Research Funding; Neovii: Honoraria, Other: Travel support; Medac: Honoraria, Other: Travel support; Novartis: Honoraria, Other: Travel support. OffLabel Disclosure: Venetoclax was used in combination with azacitidine or decitabine. The combination is not approved in the EU so far.

Background: Multiple myeloma (MM) is an incurable disease, and clinical trials with newer agents have shown improved patient outcomes. There is a need for effective and tolerable treatment for patients with relapsed/refractory MM (RRMM). Proteasome inhibitors (bortezomib, carfilzomib, ixazomib) remain an integral part of regimens used in RRMM or newly diagnosed (ND) MM. This meta-analysis aims to assess the efficacy and safety of ixazomib (Ixa) based regimens in RRMM. Methods: A comprehensive literature search was performed on PubMed, Cochrane, Embase, Web of Science, and clinicaltrials.gov. We used MeSH and Emtree terms, "ixazomib" AND "multiple myeloma" from the inception of literature till 06/01/2020. We screened 1529 articles and included 3 randomized clinical trials (RCT, N=907) and 8 non-randomized clinical trials (NRCT, N=321). We excluded case reports, case series, review articles, meta-analysis, observational studies, and clinical trials that didn't provide data about the efficacy and safety of Ixa in RRMM. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: In 11 clinical trials (N=1228), the age range of patients was 30-91 years. In Phase III RCTs (N=837) comparing Ixa + Lenalidomide (Len) + dexamethasone (Dex) vs. placebo + Len + Dex, risk ratio of overall response rate (ORR), complete response (CR), and very good partial response (VGPR) were 1.14 (95% CI=1.05-1.24, I2=80%), 1.87 (95% CI=1.17-2.99, I2=0), and 1.15 (95% CI=0.95-1.40, I2=0), respectively in favor of Ixa + Len + Dex. (Fig 1-3) Grade 3 or higher treatment-related adverse events (TRAEs) thrombocytopenia, diarrhea, and rash were reported in 20%, 5.7% and 6.4% of the patients in the Ixa group vs. 10%, 2.1%, and 2.8% in the placebo group, respectively. In a Phase II RCT by Kumar et al (N=70) comparing the Ixa dosage, 4 mg Ixa + Dex yielded an ORR of 31%, CR 2.8%, and VGPR 17.1%, while 5.5 mg Ixa yielded improved ORR of 54%, CR 2.8%, and VGPR 25.7%. In a NRCT by Costello et al. (N=6), Ixa + daratumumab (Dara) + Pom + Dex yielded 100% ORR, CR 5% (95% CI=0.17-0.83), and VGPR 50% (95% CI=0.17-0.83). ≥Grade 3 TRAEs were hypertension (16%), and hematological (33%). Among 417 patients from two RCT in single arm who received Ixa + Len + Dex, pooled ORR was 70% (95% CI=0.53-0.82, I2=84%), pooled CR 11% (95% CI=0.8-0.14, I2=0), and pooled VGPR was 29% (95% CI=0.18-0.43, I2=66%). In a NRCT by Dhakal et al. (N=19), Ixa + bendamustine + Dex yielded an ORR 58% (95% CI=0.36-0.77), CR 0, and VGPR 11% (95% CI =0.03-0.34). ≥Grade 3 TRAEs were neutropenia 31%, thrombocytopenia 52%, and diarrhea 10%. In 2 NRCT (N=106), Ixa + cyclophosphamide (Cyc) + Dex yielded a pooled ORR 52% (95% CI=0.42-0.61, I2=0), CR 4% (95% CI=0.01-0.10, I2=0), and VGPR 17% (95% CI=0.11-0.25, I2=0). ≥Grade 3 TRAEs were thrombocytopenia (15%), and upper abdominal pain (4%). In a NRCT by Ludwig et al. (N=90), Ixa + thalidomide (Thal) + Dex yielded an ORR 51% (95% CI=0.41-0.61), CR 9% (95% CI=0.5-0.17), and VGPR 14% (95% CI=0.09-0.23). ≥Grade 3 TRAEs were anemia (17.8%), and infections (16.1%). In a NRCT by Krishnan et al. (N=31), Ixa + Pomalidomide (Pom) + Dex yielded an ORR 48% (95% CI=0.32-0.65) and VGPR 16% (95% CI=0.07-0.33). (Fig 4-6) ≥Grade 3 TRAEs were neutropenia (10%), and lymphopenia (35%). In 2 NRCT by Kumar et al. (N=70) of two drugs combination, Ixa + Dex yielded a pooled ORR 43% (95% CI=0.28-0.59, I2=47%), pooled CR 1% (95% CI=0-0.09, I2=0), and pooled VGPR 24% (95% CI=0.16-0.36, I2=0). ≥Grade 3 TRAEs were hematological (28%), and non-hematological (22.8%). In 2 NRCT of Ixa monotherapy (N=69), pooled ORR was 17% (95% CI=0.10-0.28, I2=0), and pooled CR 6% (95% CI=0.2-0.22, I2=0). (Fig 4-6) ≥Grade 3 TRAEs were anemia (11%), thrombocytopenia (5.4%), and neutropenia (2.7%). Conclusion: Our study provides useful insight into relative efficacy of various Ixa regimens for the treatment of RRMM. The pooled analysis of RCT showed that the combination of Ixa + Len + Dex yielded better response as compared to placebo. In the pooled analysis of outcomes in single arm NRCT, Ixa + Dara + Pom + Dex and Ixa + Len + Dex showed better efficacy outcomes as compared to Ixa + Dex in combination with Thal, Cyc, or Bendamustin. Three drugs Ixa combination regimens had better efficacy as compared to two drugs combination of Ixa + Dex and Ixa monotherapy. Ixa was well tolerated with acceptable safety profile. Additional multicenter, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Aims/Objectives/BackgroundGlobally, injuries cause more than 5 million deaths annually. Children and young people are a particularly vulnerable group and injuries are the leading cause of death in people aged 5–24 years globally and a leading cause of disability.In most low and middle-income countries where the majority of global child injury burden occurs, systems for routinely collecting injury data are limited. There is a continuing need for better data on childhood injuries and for injury surveillance.The aim of our study was to introduce a hospital-based injury surveillance tool – the first of its kind in Nepal and explore its feasibility. We undertook prospective collection of data on all injuries/trauma presenting to 2 hospital emergency departments to describe the epidemiology of paediatric hospital injury presentations and associated risk factors.Methods/DesignA new injury surveillance system for use in emergency departments in Nepal was designed and used to collect data on patients presenting with injuries. Data were collected prospectively in two hospitals 24 h a day over 12 months (April 2019 - March 2020) by trained data collectors using tablet computers.Abstract 432 Table 1Socio-demographic profile and characteristics of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020 (N=2696)CharacteristicsFrequencyGender Male 1778 Female 918 Age groups 0–4 years 653 5–9 years 866 10–14 years 680 15–17 years 497 Median year (IRQ) 8 (5 – 13) Ethnicity/caste Janajati 1384 Brahmin/Chhetri 892 Dalit 148 Madhesi 146 Muslim 74 Others 50 Unknown 2 Place where injury occurred Home/Compound 1576 Highway/road/street 636 School 233 Recreational area 138 Workplace 76 Other 37 Activities at the time injury occurred Leisure/Play 1889 Travelling (other than to/from school/work) 296 Work 202 Travelling (to/from school/work) 184 Education 42 Organised sports 11 Other 52 Unknown 20 Intent of injury Unintentional 2560 Intentional (self-harm) 61 Intentional (assault) 75 Unintentional (n=2560) Fall 912 Animal or insect related 728 Road traffic injury 356 Injured by a blunt force 201 Stabbed, cut or pierced 176 Fire, burn or scald 65 Poisoning 52 Suffocation/choking 36 Electrocution 12 Drowning and submersion 7 Other 13 Unknown 2 Self-harm (n=61) Poisoning 38 Hanging, strangulation, suffocation 12 Stabbed, cut or pierced 6 Injured by blunt object 4 Other 1 Assault (n=75) Bodily force (physical violence) 43 Injured by blunt object 18 Stabbed, cut or pierced 8 Pushing from a high place 2 Poisoning 2 Sexual assault 1 Other 1 Nature of injury (one most severe) Cuts, bites or open wound 1378 Bruise or superficial injury 383 Fracture 299 Sprain, strain or dislocation 243 Internal injury 124 Head Injury/Concussion 83 Burns 67 Other 115 Unknown 2 Not recorded 2 Severity of injury No apparent injury 125 Minor 1645 Moderate 813 Severe 111 Not recorded 2 Disposition Discharged 2317 Admitted to hospital 164 Transferred to another hospital 179 Died 21 Leave Against Medical Advice (LAMA) 11 Unknown 2 Not recorded 2 Note:Not recorded = missing cases95% CI calculated using one proportion test and normal approximation method in Minitab.Abstract 432 Table 2Distribution of injuries by age-group, sex and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups & Sex0 - 4 years5 - 9 years10–14 years15–17 yearsMaleFemaleTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 239 (26.2) 328 (36.0) 249 (27.3) 96 (10.5) 636 (69.7) 276 (30.3) 912 (100) Animal or insect related 175 (24.0) 260 (35.7) 190 (26.1) 103 (14.1) 470 (64.6) 258 (35.4) 728 (100) Road traffic injury 49 (13.8) 108 (30.3) 86 (24.2) 113 (31.7) 223 (62.6) 133 (37.4) 356 (100) Injured by a blunt force 54 (26.9) 74 (36.8) 49 (24.4) 24 (11.9) 150 (74.6) 51 (25.4) 201 (100) Stabbed, cut or pierced 20 (11.4) 56 (31.8) 49 (27.8) 51 (29.0) 127 (72.2) 49 (27.8) 176 (100) Fire, burn or scald 42 (64.6) 10 (15.4) 9 (13.8) 4 (6.2) 27 (41.5) 38 (58.5) 65 (100) Poisoning 33 (63.5) 6 (11.5) 5 (9.6) 8 (15.4) 26 (50.0) 26 (50.0) 52 (100) Suffocation/choking 24 (66.7) 5 (13.9) 2 (5.6) 5 (13.9) 20 (55.6) 16 (44.4) 36 (100) Electrocution 2 (15.7) 0 (0.0) 3 (25.0) 7 (58.3) 10 (83.3) 2 (16.7) 12 (100) Drowning and submersion 1 (14.3) 1 (14.3) 3 (42.9) 2 (28.6) 3 (42.9) 4 (57.1) 7 (100) Other 6 (46.2) 4 (30.8) 3 (23.1) 0 (0.0) 10 (76.9) 3 (23.1) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) 2 (100) Total 647 (25.3) 852 (33.3) 648 (25.3) 413 (16.1) 1702 (66.5) 858 (33.5) 2560 (100) Self-harm Poisoning 0 (0.0) 0 (0.0) 6 (15.8) 32 (84.2) 7 (18.4) 31 (81.6) 38 (100) Hanging 0 (0.0) 0 (0.0) 3 (25.0) 9 (75.0) 4 (33.3) 8 (66.7) 12 (100) Stabbed, cut or pierced 0 (0.0) 0 (0.0) 2 (33.3) 4 (66.7) 1 (16.7) 5 (83.3) 6 (100) Injured by blunt object 0 (0.0) 2 (50.0) 2 (50.0) 0 (0.0) 4 (100) 0 (0.0) 4 (100) Other 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) 0 (0.0) 1 (100) Total 0 (0.0) 2 (3.3) 13 (21.3) 46 (75.4) 17 (27.9) 44 (72.1) 61 (100) Assault Bodily force (physical violence) 3 (7.0) 1 (2.3) 11 (25.6) 28 (65.1) 37 (86.0) 6 (14.0) 43 (100) Injured by blunt object 2 (11.1) 8 (44.4) 4 (22.2) 4 (22.2) 13 (72.2) 5 (27.8) 18 (100) Stabbed, cut or pierced 1 (12.5) 0 (0.0) 2 (25.0) 5 (62.5) 7 (87.5) 1 (12.5) 8 (100) Pushing from a high place 0 (0.0) 1 (50.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 2 (100) Poisoning 0 (0.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 1 (50.0) 2 (100) Sexual assault 0 (0.0) 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Other 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Total 6 (8.0) 12 (16.0) 19 (25.3) 38 (50.7) 59 (78.7) 16 (21.3) 75 (100) Abstract 432 Table 3Association of injury location, nature and severity with age among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups0 – 4 years5 – 9 years10–14 years15–17 yearsTotalChi-SquareInjury characteristicsn (%)n (%)n (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 537 (34.1) 504 (32.0) 319 (20.2) 216 (13.7) 1576 (100) <0.001 Highway/road/street 85 (13.4) 196 (30.8) 190 (29.9) 165 (25.9) 636 (100) School 15 (6.4) 107 (45.9) 85 (36.5) 26 (11.2) 233 (100) Recreational area 9 (6.5) 44 (31.9) 55 (39.9) 30 (21.7) 138 (100) Workplace 1 (1.3) 4 (5.3) 19 (25.0) 52 (68.4) 76 (100) Other 6 (16.2) 11 (29.7) 12 (32.4) 8 (21.6) 37 (100) Total 653 (24.2) 866 (32.1) 680 (25.2) 497 (18.4) 2696 (100) Nature of injury Cuts, bites or open wound 328 (23.8) 506 (36.7) 314 (22.8) 230 (16.7) 1378 (100) <0.001 Bruise or superficial injury 81 (21.1) 99 (25.8) 118 (30.8) 85 (22.2) 383 (100) Fracture 48 (16.1) 101 (33.8) 112 (37.5) 38 (12.7) 299 (100) Sprain, strain or dislocation 48 (19.8) 78 (32.1) 72 (29.6) 45 (18.5) 243 (100) Internal injury 44 (35.5) 8 (6.5) 18 (14.5) 54 (43.5) 124 (100) Head Injury/Concussion 18 (21.7) 26 (31.3) 18 (21.7) 21 (25.3) 83 (100) Burns 42 (62.7) 9 (13.4) 10 (14.9) 6 (9.0) 67 (100) Other 41 (35.7) 38 (33.0) 18 (15.7) 18 (15.7) 115 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Severity of injury No apparent injury 39 (31.2) 45 (36.0) 26 (20.8) 15 (12.0) 125 (100) <0.001 Minor 419 (25.5) 535 (32.5) 406 (24.7) 285 (17.3) 1645 (100) Moderate 171 (21.0) 262 (32.2) 225 (27.7) 155 (19.1) 813 (100) Severe 23 (20.7) 23 (20.7) 23 (20.7) 42 (37.8) 111 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Abstract 432 Table 4Association of injury location, nature and severity with sex among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020SexMaleFemaleTotalChi-SquareInjury characteristicsn (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 979 (62.1) 597 (37.9) 1576 (100) <0.001 Highway/road/street 421 (66.2) 215 (33.8) 636 (100) School 176 (75.5) 57 (24.5) 233 (100) Recreational area 111 (80.4) 27 (19.6) 138 (100) Workplace 62 (81.6) 14 (18.4) 76 (100) Other 29 (78.4) 8 (21.6) 37 (100) Total 1778 (65.9) 918 (34.1) 2696 (100) Nature of injury Cuts, bites or open wound 959 (69.6) 419 (30.4) 1378 (100) <0.001 Bruise or superficial injury 246 (64.2) 137 (35.8) 383 (100) Fracture 200 (66.9) 99 (33.1) 299 (100) Sprain, strain or dislocation 154 (63.4) 89 (36.6) 243 (100) Internal injury 50 (40.3) 74 (59.7) 124 (100) Head Injury/Concussion 59 (71.1) 24 (28.9) 83 (100) Burns 27 (40.3) 40 (59.7) 67 (100) Other 79 (68.7) 36 (31.3) 115 (100) Unknown 2 (100) 0 (0.0) 2 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Severity of injury No apparent injury 81 (64.8) 44 (35.2) 125 (100) 0.048 Minor 1102 (67.0) 543 (33.0) 1645 (100) Moderate 533 (65.6) 280 (34.4) 813 (100) Severe 60 (54.1) 51 (45.9) 111 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Abstract 432 Table 5Distribution of injuries by outcome and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Outcome of injuryDischargedAdmittedTransferredDiedLAMAUnknownTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 787 (86.5) 65 (7.1) 53 (5.8) 0 (0.0) 4 (0.4) 1 (0.1) 910 (100) Animal/insect bite/sting 704 (96.7) 3 (0.4) 19 (2.6) 0 (0.0) 1 (0.1) 1 (0.1) 728 (100) Road traffic injury 260 (73.0) 47 (13.2) 44 (12.4) 5 (1.4) 0 (0.0) 0 (0.0) 356 (100) Injured by a blunt force 190 (94.5) 4 (2.0) 6 (3.0) 0 (0.0) 1 (0.5) 0 (0.0) 201 (100) Stabbed, cut or pierced 165 (93.8) 8 (4.5) 3 (1.7) 0 (0.0) 0 (0.0) 0 (0.0) 176 (100) Fire, burn or scald 52 (80.0) 12 (18.5) 1 (1.5) 0 (0.0) 0 (0.0) 0 (0.0) 65 (100) Poisoning 30 (57.7) 4 (7.7) 16 (30.8) 1 (1.9) 1 (1.9) 0 (0.0) 52 (100) Suffocation/choking/asphyxia 24 (66.7) 4 (11.1) 6 (16.7) 1 (2.8) 1 (2.8) 0 (0.0) 36 (100) Electrocution 7 (58.3) 2 (16.7) 2 (16.7) 1 (8.3) 0 (0.0) 0 (0.0) 12 (100) Drowning and submersion 4 (57.1) 0 (0.0) 0 (0.0) 3 (42.9) 0 (0.0) 0 (0.0) 7 (100) Other 12 (92.3) 1 (7.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 2237 (87.5) 150 (5.9) 150 (5.9) 11 (0.4) 8 (0.3) 2 (0.1) 2558 (100) Self-harm Poisoning 5 (13.2) 8 (21.1) 23 (60.5) 0 (0.0) 2 (5.3) 0 (0.0) 38 (100) Hanging 1 (8.3) 0 (0.0) 1 (8.3) 10 (83.3) 0 (0.0) 0 (0.0) 12 (100) Stabbed, cut or pierced 6 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 6 (100) Injured by blunt object 4 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 17 (27.9) 8 (13.1) 24 (39.3) 10 (16.4) 2 (3.3) 0 (0.0) 61 (100) Assault Bodily force (physical violence) 34 (79.1) 5 (11.6) 3 (7.0) 0 (0.0) 1 (2.3) 0 (0.0) 43 (100) Injured by blunt object 18 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 18 (100) Stabbed, cut or pierced 6 (75.0) 1 (12.5) 1 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 8 (100) Pushing from a high place 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Poisoning 1 (50) 0 (0.0) 1 (50.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Sexual assault 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 63 (84.0) 6 (8.0) 5 (6.7) 0 (0.0) 1 (1.3) 0 (0.0) 75 (100) Abstract 432 Figure 1Seasonal variation of injuries identified by the injury surveillance system over a year among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Results/ConclusionsThe total number of ED patients with injury in the study was 10,154.2,696 were patients aged <18 years. Most injuries in children were unintentional and over half of children presenting with injuries were <10 years of age. Falls, animal bites/stings and road traffic injuries accounted for nearly 75% of all injuries with some (drowning, poisonings and burns) under-represented. Over half of injuries were cuts, bites and open wounds. The next most common injury types were superficial injuries (14.2%); fractures (11.1%); sprains/dislocations (9.0%). Child mortality was 1%.This is the biggest prospective injury surveillance study in a low or middle country in recent years and supports the use of injury surveillance in Nepal for reducing child morbidity and mortality through improved data.CHILD PAPER: RESULTS SECTIONTotal number of ED patients: 33046Total number of ED patient with injury: 10154 (adult=7458 & children=2696)8.2% (n=2696) patients with injury were children aged <18 yearsHetauda hospital: 2274 (84.3%)Chure hill hospital: 422 (15.7%)

Abstract Introduction Effective recruitment and subsequent enrollment of diverse populations is often a challenge in randomized controlled trials, especially those focused on weight loss. In the civilian literature, individuals identified as racial and ethnic minorities, men, and younger and older adults are poorly represented in weight loss interventions. There are limited weight loss trials within military populations, and to our knowledge, none reported participant characteristics associated with enrollment. There may be unique motives and barriers for active duty personnel for enrollment in weight management trials. Given substantial costs and consequences of overweight and obesity in the U.S. military, identifying predictors and limitations to diverse enrollment can inform future interventions within this population. The study aims to describe the recruitment, screening, and enrollment process of a military weight loss intervention. Demographic and lifestyle characteristics of military personnel lost between screening and randomization are compared to characteristics of personnel randomized in the study and characteristics of the Air Force in general. Materials and Methods The Fit Blue study, a randomized controlled behavioral weight loss trial for active duty personnel, was approved by the Institutional Review Board of the Wilford Hall Ambulatory Surgical Center in San Antonio, TX, USA and acknowledged by the Institutional Review Board at the University of Tennessee Health Science Center. Logistic regressions compared participant demographics, anthropometric data, and health behaviors between personnel that attended a screening visit but were not randomized and those randomized. Multivariable models were constructed for the likelihood of being randomized using a liberal entry and stay criteria of 0.10 for the p-values in a stepwise variable selection algorithm. Descriptive statistics compared the randomized Fit Blue cohort demographics to those of the U.S. Air Force Results In univariate analyses, older age (p < 0.02), having a college degree or higher (p < 0.007) and higher military rank (p < 0.02) were associated with completing the randomization process. The randomized cohort reported a lower percentage of total daily kilocalories for fat compared to the non-randomized cohort (p = 0.033). The non-randomized cohort reported more total minutes and intensity of physical activity (p = 0.073). In the multivariate model, only those with a college degree or higher were 3.2 times more likely to go onto randomization. (OR = 3.2, 95% CI = 2.0, 5.6, p < 0.0001). The Fit Blue study included a higher representation of personnel who identified as African American (19.4% versus 15.0%) and Hispanic/Latino (22.7% versus 14.3%) compared with the U.S. Air Force in general; however, men were underrepresented (49.4% versus 80.0%). TABLE I.Comparisons of Demographic Characteristics of Randomized Fit Blue Cohort to Screened Non-Randomized CohortFit Blue Randomized Participants (N = 248)Non-Randomized Cohort (N = 111)All Screened Participants (N = 359)p-ValueSex N (%)0.73 Male122 (49.2)52 (46.8)174 (48.5) Female126 (50.8)59 (53.2)183 (51.5)Age Mean (±SD) years34 (±7.5)32 (±6.7)33 (±7.3)0.02Race N (%)0.89 African American49 (19.8)22 (19.8)71 (19.8) Caucasian163 (65.7)75 (67.6)238 (66.3) Other36 (14.5)14 (12.2)50 (13.9)Ethnicity N (%)0.59 Hispanic/Latino56 (22.6)28 (25.2)84 (23.4) Non-Hispanic/Latino192 (77.4)83 (74.8)275 (76.6)Education N (%)<0.0001 Less than college degree123 (49.6)82 (73.9)205 (57.1) College degree or greater125 (50.4)29 (26.1)154 (42.9)Marital status N (%)0.83 Single/never married40 (16.1)20 (18)60 (16.7) Married/living as married169 (68.1)72 (64.9)241 (67.1) Separated/divorced39 (15.7)19 (17.1)58 (16.2)Number of additional adults in household N (%)0.82 046 (18.5)22 (19.8)68 (18.9) 1162 (65.3)73 (65.8)235 (65.5) 231 (12.5)14 (12.6)45 (12.5) 3 or more9 (3.6)2 (1.8)11 (3.1)Number of children in household N (%)0.56 091 (36.7)37 (33.3)128 (35.7) 159 (23.8)23 (20.7)82 (22.8) 257 (23)26 (23.4)83 (23.1) 3 or more41 (16.5)25 (22.5)66 (18.4)Years in service mean (± SD)12 (±6.6)11 (±6.1)12 (±6.4)0.20Military gradeaN (%)0.02 E1–E434 (13.7)19 (17.1)53 (14.8) E5–E6105 (42.3)58 (52.3)163 (45.4) E7–E952 (21)21 (18.9)73 (20.3) O1–O317 (6.9)9 (8.1)26 (7.2) O4–O639 (15.7)4 (3.6)43 (12)Branch0.68 Army4 (1.6)1 (0.9)5 (1.4) Air Force234 (94.4)105 (94.6)339 (94.4) Navy8 (3.2)5 (4.5)13 (3.6) Marine Corp2 (0.8)0 (0.0)2 (0.6)BMI (m2/kg) N (%)30.6 (±2.7)30.4 (±2.9)30.6 (±2.8)BMI category N (%)0.76 Overweight115 (46.4)52 (48.1)167 (46.9) Obese133 (53.6)56 (51.9)189 (53.1)aMilitary ranking; Enlisted (E) categories: E1–E4 (enlisted), E5–E6 (non-commissioned officers), E7–E9 (senior non-commissioned officers) and two Officer categories (O): O1–O3 (Company Grade Officer) and O4–O6 (Field Grade Officer); standard deviation (SD).Table II.Comparisons of Anthropometric Characteristics of Randomized Fit Blue Cohort to Screened Non-Randomized CohortFit Blue Randomized Participants (N = 248)Non-Randomized Cohort (N = 111)All Screened Participants (N = 359)p-ValuePhysical activity Total physical activity2525 (±3218)2840 (±2541)2621 (±3028)0.027 (mean (±SD) minutes per week) Total sedentary physical activity5046 (±239)472 (±221)494 (±234)0.35 (mean (±SD) minutes per week) Vigorous physical activity34 (±145)54 (±152)40 (±147)0.036 (mean (±SD) minutes per week)Dietary intake Total sweetened beverages (kcal per day)165 (±206)152.9 (±166)160.8 (±194)0.80 Fruit and vegetable consumption (cups per day)3 (±1)3 (±1)3 (±1)0.52 Dietary fat (% total kcal)35 (±4)34 (±4)35 (±4)0.033 Conclusions Accounting for all influencing characteristics, higher educational status was the only independent predictor of randomization. Perhaps, highly educated personnel are more invested in a military career, and thus, more concerned with consequences of failing required fitness tests. Thus, it may be important for future weight loss interventions to focus recruitment on less-educated personnel. Results suggest that weight loss interventions within a military population offer a unique opportunity to recruit a higher prevalence of males and individuals who identify as racial or ethnic minorities which are populations commonly underrepresented in weight loss research.

Abstract Introduction: The myelodysplastic syndromes (MDS) are a group of clonal diseases derived from hematopoietic stem cells (HSC). Colony-forming unit cell (CFU-C) assay is an effective method to study the number and the function of HSC in vitro. In this study, we focus on the characteristics and the prognostic value of CFU-C in patients with MDS. Patients and Method: CFU-C assays were performed according to the protocol of MethoCultTM H4435 Enriched (STEMCELL Technologies). A colony was defined as an aggregate of >40 cells. Clusters consisted of 4 to 40 cells. 560 consecutive newly-diagnosed, untreated subjects with MDS diagnosed from March, 2001 to April, 2013 were studied. All subjects were reclassified according to the 2008 WHO criteria. 535 subjects with evaluable cytogenetics were classified using the International Prognostic Scoring System (IPSS) and the revised International Prognostic Scoring System (IPSS-R) criteria. Follow-up data were available for 470£¨84%£©subjects. Median follow-up of survivors was 26 months (range, 1-170) months. Subjects receiving an allotransplants were censored in survival analyses. Erythroid and myeloid colonies were isolated from each subject with one cytogenetic abnormality such as del(5/5q-) or +8. Cytogenetic abnormalities of each colony were analyzed by fluorescence in situ hybridization (FISH). SPSS 17.0 software was used to make statistical analysis. Results: Frequencies of burst-forming units-erythroid (BFU-E), colony forming unit-erythroid (CFU-E) and colony forming unit-granulocytes/macrophages (CFU-G/M) were significantly lower than normals (P<0.05) (Table 1). Subjects classified as lower risk in IPSS and IPSS-R had significantly higher numbers of BFU-E and CFU-E (P<0.05) but similar numbers CFU-G/M and clusters-G/M compared with higher risk subjects (Table 2). In 11 subjects with del(-5/5q-) or +8 identified by G- and/or R-banding, both normal and abnormal CFU-Cs were identified in 8 subjects studied by FISH. A high ratio of cluster- to CFU-G/M (>0.6) was associated with poor-risk cytogenetics (Table 2) and with worse overall survival in univariable (Figure 1, P=0.001) and multivariable analyses (HR 1.748, [1.01-3.0]; P=0.046) after adjusting for IPSS. Conclusions: These data suggest abnormalities of proliferation and differentiation of erythroid and myeloid precursor cells in vitro parallel the ineffective hematopoiesis typical of MDS and may be useful in predicting outcomes of patients with MDS. Table 1. CFU-C in MDS subtypes N BFU-E CFU-E CFU-G/M N Ratio of cluster- to CFU-G/M RA 21 8 (0-44) 40 (0-134) 14 (0-127)1 6 0.25 (0.40-1.00) RT 4 18 (4-55) 75 (60-90)1 30 (18-70)1 2 2 RARS 27 12 (0-33) 35 (1-140) 12 (0-70)1 10 0.45 (0.17-0.80) RCMD 275 10 (0-80) 33 (0-178) 14 (0-100) 126 0.35 (0-0.83) RAEB1 112 10 (0-258) 32 (0-312) 14 (0-89) 53 0.47 (0-1.00) RAEB2 103 9 (0-46) 25 (0-120) 13 (0-72) 42 0.37 (0-1.00) MDS-U 15 4 (0-58) 25 (0-161) 10 (0-43) 3 2 Del(5q) 3 2 (2-4) 15 (0-20) 5 (5-41)1 1 2 1No significant difference compared with normals. 2Too few cases to analyze. Table 2. Associations between CFU-C and clinical and laboratory variables N BFU-E P CFU-E P CFU-G/M P Number Ratio of cluster- to CFU-GM P IPSS 0.064 0.006 0.361 0.089 Low 30 13 (0-44) 60 (0-169) 19 (0-45) 10 0.44 (0.24-0.70) Int-1 361 10 (0-258) 33 (0-312) 14 (0-127) 150 0.33 (0-1.00) Int-2 115 9 (0-61) 30 (0-137) 14 (0-72) 52 0.45 (0-1.00) High 29 7 (0-34) 21 (0-93) 12 (0-67) 12 0.44 (0-1.00) IPSS-R 0.003 0.003 0.125 0.209 Very low 7 16 (9-25) 30 (15-120) 18 (5-33) 2 0.29 (0.10-0.49) Low 130 14 (0-80) 42 (0-178) 17 (0-70) 48 0.31 (0-0.77) Intermediate 173 10 (0-66) 34 (0-161) 13 (0-127) 81 0.37 (0-1.00) High 139 9 (0-259) 29 (0-312) 11 (0-89) 51 0.33 (0-1.00) Very high 86 8 (0-61) 25 (0-137) 14 (0-91) 42 0.47 (0-1.00) Cytogenetics (IPSS) 0.867 0.055 0.290 0.007 Good 327 10 (0-258) 36 (0-312) 15 (0-89) 133 0.33 (0-1.00) Intermediate 133 10 (0-69) 30 (0-162) 12 (0-127) 63 0.45 (0-1.00) Poor 75 10 (0-61) 25 (0-137) 14 (0-91) 28 0.42 (0-1.00) Cytogenetics (IPSS-R) 0.990 0.090 0.676 0.022 Very good 7 11 (4-20) 48 (1-110) 14 (8-28) 2 0.49 (0.43-0.56) Good 324 10 (0-258) 35 (0-312) 15 (0-89) 132 0.33 (0-1.00) Intermediate 129 10 (0-69) 30 (0-162) 12 (0-127) 62 0.45 (0-1.00) Poor 27 10 (0-61) 35 (0-137) 16 (0-48) 8 0.36 (0.15-1.00) Very poor 48 11 (0-42) 22 (0-120) 14 (0-91) 20 0.53 (0-1.00) Figure 1. Overall survival in subjects with cluster- to CFU-G/M ratios ¡Ü or > 60%. Figure 1. Overall survival in subjects with cluster- to CFU-G/M ratios ¡Ü or > 60%. Disclosures No relevant conflicts of interest to declare.

Background:Idiopathic inflammatory myopathies (IIM) are heterogeneous groups of connective tissue diseases. Diagnosis of IIM is sometimes challenging, but newly defined myositis specific autoantibodies (MSAs) are helpful in diagnosing of IIM and revealing the clinical signs [1].Objectives:To describe demographic and clinical features of IIMs and to evaluate the frequency and clinical associations of myositis-specific and myositis associated antibodies (MAAs) in IIM.Methods:Samples obtained from patients tested for MSA/MAA as of 2017 to 2020 were retrospectively evaluated. Patients were diagnosed with IIM according to clinician diagnosis. The prevalence and clinical associations of myositis-related antibodies were assessed with univariate and multivariate analysis.Results:152 patients (70.4% female) were tested for myositis-related antibodies during the study period. 81 patients were diagnosed with IIM (38 DM, 43PM). DM patients were diagnosed at an earlier age and its association with malignancy was more relevant, although the relationship with malignancy was not statistically significant. Differences of clinical characteristics between DM and PM patients were skin features which were more frequent in DM, and interstitial lung disease which was more common in PM patients.MSAs/MAAS were found in 65.4% and 43.2% in IIM patients, more frequently than patients without IIM (p=0.000 and 0.0225, respectively). MSAs were equally frequent in both IIM groups, whereas MAAs were more common in the PM group (although no significant difference in overlap with other connective tissue diseases within these two diseases). The most common MSAs in DM were anti-TIF1-γ (23%), anti-MDA5 (16%), anti-NXP2 (13%) and in PM were anti-Jo-1 (28%), anti-MDA5 (12%), anti-ku (12%), anti-PL7 (12%) respectively. Predictors of ILD in IIM were Anti-Jo-1 positivity and age (RR:10 [CI:2-41] p=0.003 and RR:1.07 [CI:1.02-1.12] p=0.04 respectively)Conclusion:The general characteristics of DM and PM patients and the frequencies of myositis-specific autoantibodies were similar to the literature, except that anti-TIF1-γ antibodies (14%) were more common in our Turkish cohort [2].References:[1]Cruellas, M.G., et al., Myositis-specific and myositis-associated autoantibody profiles and their clinical associations in a large series of patients with polymyositis and dermatomyositis. Clinics (Sao Paulo), 2013. 68(7): p. 909-14.[2]Gonzalez-Bello, Y., et al., Myositis-Specific Antibodies and Myositis-Associated Antibodies in Patients With Idiopathic Inflammatory Myopathies From the PANLAR Myositis Study Group. J Clin Rheumatol, 2020.Table 1.Baseline characteristics of the patients with DM and PMDM (n=38)PM (n=43)PFemale, n (%)27 (71.1)29 (67.4)0.457Age at onset, years33 (15-48)47 (38-58)0.002Skeletal muscle features Muscle weakness, n (%)34 (89.5)37 (86.0)0.451 Myalgia, n (%)23 (60.5)30 (69.8)0.261 Artritis, n (%)8 (21.1)9 (20.9)0.601Skin features, n (%) Heliotrope rash, n (%)18 (47.4)0 (0)<0.001 Gottron papules, n (%)25 (65.8)0 (0)<0.001 Gottron sign, n (%)18 (47.4)0 (0)<0.001 Generalize erythema, n (%)10 (26.3)0 (0)<0.001Calcinosis, n (%)4 (10.5)1 (2.3)0.143Dysphagia, n(%)10 (26.3)12 (27.9)0.537Interstitial lung disease (ILD), n (%)8 (21.1)20 (47.6)0.012Other connective tissue diseases overlap, n (%)6 (15.8)13 (30.2)0.102Malignancies, n (%)5 (13.5)3 (7)0.275Laboratory data Creatine kinase (IU/L)505 (110-3616)801 (402-1868)0.655 C-reactive protein (mg/dl)0.3 (0.1-0.8)1.2 (0.5-2.8)<0.001 ESR (mm/h)19 (8-27)25 (17-48)0.005MAAs (Ro-52, pm-scl 100, pm-scl75), n (%)11 (28.9)24 (55.8)0.013MSAs, n (%)28 (73.7)25 (58.1)0.108 Anti- TIF1- γ, n (%)9 (23.7)2 (4.7)0.014 Anti-Jo-1, n (%)2 (5.3)12 (27.9)0.007 Anti-PL-7, n (%)05 (11.6)0.038Disclosure of Interests:None declared.

Background Limited data are available on the clinical activity of venetoclax (ven) in mantle cell lymphoma (MCL). In 2 small retrospective studies of patients (pts) with MCL previously treated with BTK inhibitors (BTKi), ven resulted in overall response rates (ORRs) of 50-53% and median overall survival (OS) of 9-14 months (Eyre et al, Haematologica 2019; Zhao et al, Am J Hematol 2020). We sought to report the clinical activity of ven and identify factors associated with outcomes in a larger cohort of pts. Methods We included pts with relapsed MCL from 12 US medical centers treated with ven alone or in combination with an antiCD20 monoclonal antibody (mAb) or a BTKi. Response was determined by the local investigator. We defined OS as time from start of ven to death. Pts not experiencing an event were censored at their last known follow up. OS was determined using the Kaplan-Meier method, and univariable (UVA) and multivariable (MVA) models were developed to identify predictors of response and OS. Results Eighty-one pts were included. Pt characteristics (Table) at diagnosis (dx) were: median age 64 years (yrs) (range 38-87), male 79%, stage III/IV 95%, Ki67 &gt;30% in 61% (available n=62), blastoid/pleomorphic histology 29% (available n=75) and ≥3 cytogenetic abnormalities 34% (available n=62). BCL2 expression was present in 93% (available n=40). Frontline treatment (tx) included intensive chemotherapy [defined as including high-dose cytarabine and/or autologous transplant (ASCT) in first remission] in 52% with ASCT in first remission in 32%. Median number of therapies prior to ven was 3 (range 1-8) including antiCD20 mAb 99%, alkylator 93%, BTKi 91%, anthracycline 58%, cytarabine 56%, and lenalidomide 37%. 55% were refractory (defined as stable (SD) or progressive disease (PD)) to last tx prior to ven. ORR to BTKi prior to ven (n=70) was 66% (complete response (CR) 20%) with median duration of tx of 6.4 months (range 0.5-69). BTKi was stopped due to PD 82% and toxicity 18%. Median time from dx to start of ven was 3.9 yrs (range 0.2-17.8). Ven was given as monotherapy in 62% (n=50) and in combination with BTKi 20% (n=16), antiCD20 mAb 14% (n=11), or other 5% (n=4). Ten pts treated with ven in combination with BTKi received prior tx with BTKi with ORR to BTKi of 40% (all PR). Ven highest dose received was 20-100 mg in 12% (n=9), 200 mg 11% (n=8), 400 mg 61% (n=46), and 800 mg 17% (n=13). Median duration of tx with ven was 2.8 months (range 0.1-30). The best response to ven was CR 18%, partial response (PR) 24%, SD 11%, and PD 47% with ORR of 42%; 19 pts (23%) did not have available data for response. ORR was not significantly different with ven monotherapy 36% (13/36) vs ven + antiCD20 mAb 56% (5/9) vs ven + BTKi 43% (6/14) (p=.559), or with ven monotherapy 36% vs combination therapy 50% (13/26) (p=.274). Ven was stopped due to PD 69%, toxicity 9%, allogeneic transplant 3% or other reasons 19%. Laboratory tumor lysis syndrome (TLS) occurred in 10 pts (12%) including 3 (3.7%) with clinical TLS. 38 pts received post-ven tx with median time from stopping ven to next tx of 0.24 months (range 0-2.2); for the 33 pts with available data, the best response to post-ven tx was CR 24%, PR 27%, SD 9% and PD 39% with ORR of 51%. For the 75 pts with available data, median OS was 12.5 months (95% CI 6-17) with 3-year OS of 13.1% (95% CI 1.4-38.0%) (Figure A). Median OS was numerically longer with ven combination (28.7 months, 95% CI 4-not reached) vs monotherapy (8.6 months, 95% CI 4.7-14.4), p=.0825 (Figure B). Median OS did not significantly differ based on response (CR/PR vs SD/PD) to prior tx with BTKi (14.4 vs 9.5 months, p=.53, Figure C) or last tx prior to ven (16.7 vs 12.4 months, p=.14, Figure D). In MVA for response, achieving CR/PR with BTKi prior to ven (vs SD/PD) was associated with response to ven (odds ratio 3.48, 95% CI 1.01-12.05, p=.049). In MVA for OS, ven combination vs monotherapy (HR 0.13, 95% CI 0.03-0.53; p=.006), longer time from dx to start of ven (&gt;4 vs ≤4 yrs) (HR 0.08, 95% CI 0.02-0.36; p=.001), and higher dose of ven (≥400 mg vs &lt;400) (HR 0.17, 95% CI 0.04-0.72; p=.016) were associated with superior OS, while longer duration of tx with BTKi (&gt;6 vs ≤6 months) (HR 3.47, 95% CI 1.10-10.99; p=.038) was associated with inferior OS. Conclusions In these high-risk and heavily pretreated pts with MCL, ven resulted in low response rate and poor OS. Ven may have a better role in MCL in earlier lines of therapy and when combined with other agents such as BTKi and/or antiCD20 mAbs. Disclosures Kamdar: Roche: Research Funding. Greenwell:Lymphoma Research Foundation: Research Funding; Acrotech Biopharma LLC, Kyowa Kirin: Consultancy. Hess:ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS, AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Portell:Acerta/AstraZeneca: Research Funding; Kite: Consultancy, Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; AbbVie: Research Funding; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding. Goldsmith:Wugen Inc.: Consultancy. Grover:Genentech: Research Funding; Tessa: Consultancy. Riedell:Morphosys: Research Funding; Celgene/Bristol-Myers Squibb Company: Honoraria, Research Funding; Verastem Oncology: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Kite Pharmaceuticals/Gilead: Honoraria, Research Funding; Bayer: Honoraria; Karyopharm Therapeutics: Honoraria. Karmali:BeiGene: Speakers Bureau; AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Takeda: Research Funding; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau. Kumar:AbbVie: Research Funding; Kite Pharmaceuticals: Honoraria, Other: Honoraria for Advisory Board; Astra Zeneca: Honoraria, Other: Honoraria for Advisory Board; Celgene: Honoraria, Other: Honoraria for Advisory Board; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Adaptive Biotechnologies,: Research Funding. Hill:Abbvie: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding. Kahl:AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Pharmacyclics LLC: Consultancy; Roche Laboratories Inc: Consultancy; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy. OffLabel Disclosure: Venetoclax is not licensed for use in mantle cell lymphoma

Bullying behaviour can have a negative impact on a child's physical and psychological health. Bullying in the classroom is a challenge for early-childhood educators. Preschool is the first place outside the home where children face social challenges when interacting with their classmates. Child-Friendly Class is the first step and part of the Children Friendly School (CSF) as a UNICEF program and an important Indonesian government policy to prevent the emergence of child bullying behaviour. This study aims to identify needs in the process of developing a Child-Friendly Classroom Management model to anticipate bullying behaviour. This research and development method uses an adaptation of the Rowntree model which includes three stages of the process and data collection techniques using interviews, questionnaires, and observation. The results of this study indicate that the preparation of an effective classroom management guidebook to create child-friendly classes needs to be followed up immediately. Several findings related to teachers' perceptions of classroom management, and child-friendly classes prove that child-friendly classes have not been implemented properly in PAUD institutions, with bullying behaviour still appearing in early childhood in PAUD institutions. PAUD teachers understand that it is important to implement classroom management but so far there has been no manual on how to manage effective classrooms as well as training related to the implementation of effective classroom management. The creation of child-friendly classes is believed to be able to help teachers suppress the emergence of bullying behaviour in early childhood. Keywords: Child-Friendly Classroom Management, Bullying Prevention, Early Childhood Education References: Allday, R. A., Hinkson-Lee, K., Hudson, T. 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Sharenting is a habit of using social media to share content that disseminates pictures, videos, information, and parenting styles for their children. The purpose of this article is to describe the sharenting phenomenon that occurs among young parents, and the importance of parenting programs, rather than protecting children's privacy. Writing articles use a qualitative approach as a literature review method that utilizes various scientific articles describing the sharenting phenomenon in various countries. The findings show that sharenting behaviour can create the spread of children's identity openly on social media and tends not to protect children's privacy and even seems to exploit children. Apart from that, sharenting can also create pressure on the children themselves and can even have an impact on online crime. This article is expected to provide benefits to parents regarding the importance of maintaining attitudes and behaviour when sharing and maintaining children's privacy and rights on social media. Keywords: Sharenting on social media, Children's Privacy, Parenting Program References: Åberg, E., & Huvila, J. (2019). Hip children, good mothers – children’s clothing as capital investment? Young Consumers, 20(3), 153–166. https://doi.org/10.1108/YC-06-2018-00816 Altafim, E. R. P., & Linhares, M. B. M. (2016). Universal violence and child maltreatment prevention programs for parents: A systematic review. Psychosocial Intervention, 25(1), 27–38. https://doi.org/10.1016/j.psi.2015.10.003 Archer, C., & Kao, K.-T. (2018). Mother, baby, and Facebook makes three: Does social media provide social support for new mothers? Media International Australia, 168(1), 122–139. https://doi.org/10.1177/1329878X18783016 Bartholomew, M. K., Schoppe-Sullivan, S. J., Glassman, M., Kamp Dush, C. 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BACKGROUND: In newly diagnosed AML, high remission rates are typically achieved with IC, but the response is often transient, and detectable residual disease in the bone marrow post-chemotherapy is predictive of early relapse. Emerging data show that the identification of ≥ 0.1% MRD by multiparameter flow cytometry (MFC) in patients with AML in remission after IC is an important prognostic marker that may help guide treatment (Tx) decisions. CC-486 is an oral hypomethylating agent that allows for extended dosing schedules to prolong drug exposure over the Tx cycle. In the QUAZAR AML-001 Maintenance Trial, Tx with CC-486 300 mg QD for 14 days/28-day Tx cycle was associated with significantly improved overall (OS) and relapse-free survival (RFS) vs. placebo (PBO) in patients (pts) with AML in first remission after induction chemotherapy ± consolidation. Samples for MFC were obtained prior to randomization and serially throughout the study to assess the impact of MRD on OS and RFS, and to evaluate rates of conversion from MRD positivity (+) to negativity (-) in the CC-486 and PBO arms. METHODS: Eligible pts aged ≥ 55 years with AML were randomized 1:1 to CC-486 300 mg or PBO within 4 months of achieving first complete remission (CR) or CR with incomplete blood count recovery (CRi). MFC assessments of bone marrow aspirates were performed centrally at screening; at cycles 3, 6, 9, 12, 15, 18, 21, 24, 30, and 36; and as clinically indicated. Samples were analyzed with a panel of 22 cell surface markers using an MRD+ cutoff of ≥ 0.1% (per ELN MRD guidelines). For pts MRD+ at baseline (BL; ie, at randomization), an MRD response was defined as achievement of MRD- for ≥ 2 consecutive assessments. MRD- duration was calculated from the time of randomization (for pts MRD- at BL) or from the first of ≥ 2 consecutive MRD- tests (for pts MRD+ at BL), until the last MRD- assessment (for pts who became MRD+) or Tx discontinuation. OS, RFS, and MRD- durations were estimated using Kaplan-Meier methods. Multivariate (MV) Cox regression analyses were performed to evaluate the association of BL MRD status (MRD+ vs. MRD-) and randomized Tx arm (CC-486 vs. PBO) with OS and RFS. RESULTS: The MRD-evaluable cohort comprised 463/472 randomized pts (98.1%; CC-486, n=236; PBO, n=227) who had samples available for evaluation at BL and at ≥ 1 post-BL visit. At BL, 43% of pts (n=103) in the CC-486 arm and 50% (n=116) in the PBO arm were MRD+. Overall, BL characteristics were similar between MRD+ and MRD- pts: median ages were 69 (range 55-84) and 68 (55-86) years, respectively; 84% and 88% had intermediate-risk cytogenetics at diagnosis; 52% and 46% of pts had an ECOG PS of 0; and 79% and 82% received ≥ 1 cycle of consolidation after induction. CC-486 Tx resulted in improved OS from time of randomization compared with PBO in pts who were either MRD+ (median 14.6 vs. 10.4 mo, respectively; HR 0.69 [95%CI 0.51, 0.93]) or MRD- (median 30.1 vs. 24.3 mo; HR 0.81 [0.59, 1.12]) at BL. Median RFS was also extended with CC-486 vs. PBO for both MRD+ (7.1 vs. 2.7 mo, respectively; HR 0.58 [95%CI 0.43, 0.78]) and MRD- pts (13.4 vs. 7.8 mo; HR 0.71 [0.52, 0.98]). In MV analyses, BL MRD status (MRD+ vs. MRD-) was significantly associated with OS (HR 1.85; P &lt; 0.0001) and RFS (HR 2.04; P &lt; 0.0001), and CC-486 showed a significant Tx benefit vs. PBO on both OS (HR 0.74; P = 0.0067) and RFS (HR 0.63; P &lt; 0.0001) independent of MRD status at BL (Figure). The median duration of MRD negativity was extended with CC-486 vs. PBO: 11.0 vs. 5.0 mo, respectively (HR 0.62 [95%CI 0.48, 0.78]). Tx with CC-486 also resulted in a higher rate of MRD response (MRD+ to MRD-) vs. PBO: 37% vs. 19%, respectively. Among MRD responders, 9/38 patients (24%) in the CC-486 arm achieved MRD negativity &gt; 6 mo after randomization, compared with only 1/22 patients (5%) in the PBO arm. CONCLUSIONS: The QUAZAR AML-001 Maintenance Trial was the first prospective, randomized trial to include long-term longitudinal assessment of MRD in older patients with AML in remission. In both treatment arms, MRD+ status (≥ 0.1%) after induction ± consolidation was associated with significantly shorter OS and RFS compared with MRD- status. Approximately one-fourth of MRD responders treated with CC-486 achieved MRD negativity &gt; 6 mo after study entry, suggesting that CC-486 could induce MRD negativity after prolonged MRD+ status. Maintenance Tx with CC-486 substantially improved OS and RFS independent of MRD status at BL. Disclosures Roboz: Otsuka: Consultancy; AstraZeneca: Consultancy; Orsenix: Consultancy; Astellas: Consultancy; Argenx: Consultancy; Actinium: Consultancy; Sandoz: Consultancy; Roche/Genentech: Consultancy; Jazz: Consultancy; Eisai: Consultancy; Celltrion: Consultancy; MEI Pharma: Consultancy; Helsinn: Consultancy; Epizyme: Consultancy; Jasper Therapeutics: Consultancy; Cellectis: Research Funding; Trovagene: Consultancy; Takeda: Consultancy; Astex: Consultancy; Amphivena: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Bayer: Consultancy; Array BioPharma: Consultancy; Daiichi Sankyo: Consultancy. Ravandi:Abbvie: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Macrogenics: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Orsenix: Consultancy, Honoraria, Research Funding. Wei:Pfizer: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria; Walter and Eliza Hall Institute of Medical Research: Patents & Royalties: AW is eligible for royalty payments related to venetoclax; Roche: Honoraria; Amgen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau; Abbvie: Honoraria, Research Funding, Speakers Bureau; Servier: Consultancy, Honoraria, Research Funding; Macrogenics: Honoraria; Astra Zeneca: Honoraria, Research Funding. Dombret:Menarini: Consultancy; Janssen: Consultancy; Cellectis: Consultancy; Shire-Baxalta: Consultancy; Immunogen: Consultancy; Otsuka: Consultancy; Abbvie: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Servier: Consultancy, Research Funding; Sunesis: Consultancy; Amgen: Consultancy, Research Funding; Jazz Pharma: Consultancy, Research Funding; Celgene: Consultancy; Nova: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Döhner:Astex: Consultancy, Honoraria; Astellas: Consultancy, Honoraria, Research Funding; AROG: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; GEMoaB: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Oxford Biomedicals: Consultancy, Honoraria; Sunesis: Research Funding; Pfizer: Research Funding; Roche: Consultancy, Honoraria; Jazz: Consultancy, Honoraria, Research Funding; Helsinn: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Thol:Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. Voso:Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Porkka:Novartis: Consultancy, Honoraria, Research Funding; BMS/Celgene: Honoraria, Research Funding. La Torre:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Skikne:Bristol Myers Squibb: Current Employment. Kumar:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Dong:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Beach:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Risueño:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: Named in BMS (before Celgene) patent filings related to predictive patient response biomarkers in hematological malignancies. Lopes de Menezes:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Ossenkoppele:Novartis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Roche: Consultancy; J&J: Consultancy, Research Funding; Agios: Consultancy; Jazz: Consultancy; Astellas: Consultancy; Daiichi Sayko: Consultancy; Amgen: Consultancy.

This article provides the review of the medical use of pH- and temperature-sensitive polymer hydrogels. Such polymers are characterised by their thermal and pH sensitivity in aqueous solutions at the functioning temperature of living organisms and can react to the slightest changes in environmental conditions. Due to these properties, they are called stimuli-sensitive polymers. This response to an external stimulus occurs due to the amphiphilicity (diphilicity) of these (co)polymers. The term hydrogels includes several concepts of macrogels and microgels. Microgels, unlike macrogels, are polymer particles dispersed in a liquid and are nano- or micro-objects. The review presents studies reflecting the main methods of obtainingsuch polymeric materials, including precipitation polymerisation, as the main, simplest, and most accessible method for mini-emulsion polymerisation, microfluidics, and layer-by-layer adsorption of polyelectrolytes. Such systems will undoubtedly be promising for use in biotechnology and medicine due to the fact that they are liquid-swollen particles capable of binding and carrying various low to high molecular weight substances. It is also important that slight heating and cooling or a slight change in the pH of the medium shifts the system from a homogeneous to a heterogeneous state and vice versa. This providesthe opportunity to use these polymers as a means of targeted drug delivery, thereby reducing the negative effect of toxic substances used for treatment on the entire body and directing the action to a specific point. In addition, such polymers can be used to create smart coatings of implanted materials, as well as an artificial matrix for cell and tissue regeneration, contributing to a significant increase in the survival rate and regeneration rate of cells and tissues. References 1. Gisser K. R. C., Geselbracht M. J., Cappellari A.,Hunsberger L., Ellis A. B., Perepezko J., et al. 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Climate change induced sea-level rise (SLR) is on its increase globally. Regionally the lowlands of China, Vietnam, Bangladesh, and islands of the Malaysian, Indonesian and Philippine archipelagos are among the world’s most threatened regions. Sea-level rise has major impacts on the ecosystems and society. It threatens coastal populations, economic activities, and fragile ecosystems as mangroves, coastal salt-marches and wetlands. This paper provides a summary of the current state of knowledge of sea level-rise and its effects on both human and natural ecosystems. The focus is on coastal urban areas and low lying deltas in South-East Asia and Vietnam, as one of the most threatened areas in the world. About 3 mm per year reflects the growing consensus on the average SLR worldwide. The trend speeds up during recent decades. The figures are subject to local, temporal and methodological variation. In Vietnam the average values of 3.3 mm per year during the 1993-2014 period are above the worldwide average. Although a basic conceptual understanding exists that the increasing global frequency of the strongest tropical cyclones is related with the increasing temperature and SLR, this relationship is insufficiently understood. Moreover the precise, complex environmental, economic, social, and health impacts are currently unclear. SLR, storms and changing precipitation patterns increase flood risks, in particular in urban areas. Part of the current scientific debate is on how urban agglomeration can be made more resilient to flood risks. Where originally mainly technical interventions dominated this discussion, it becomes increasingly clear that proactive special planning, flood defense, flood risk mitigation, flood preparation, and flood recovery are important, but costly instruments. Next to the main focus on SLR and its effects on resilience, the paper reviews main SLR associated impacts: Floods and inundation, salinization, shoreline change, and effects on mangroves and wetlands. The hazards of SLR related floods increase fastest in urban areas. This is related with both the increasing surface major cities are expected to occupy during the decades to come and the increasing coastal population. In particular Asia and its megacities in the southern part of the continent are increasingly at risk. The discussion points to complexity, inter-disciplinarity, and the related uncertainty, as core characteristics. An integrated combination of mitigation, adaptation and resilience measures is currently considered as the most indicated way to resist SLR today and in the near future.References Aerts J.C.J.H., Hassan A., Savenije H.H.G., Khan M.F., 2000. Using GIS tools and rapid assessment techniques for determining salt intrusion: Stream a river basin management instrument. 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Abstract Background Coronary flow velocity reserve (CFVR) and heart rate reserve (HRR) during vasodilator stress echocardiography (SE) assess coronary microvascular function and cardiac sympathetic reserve respectively. Both CFVR and HRR can be impaired in hypertrophic cardiomyopathy (HCM). Objectives To evaluate the prognostic value of CFVR and HRR during vasodilator SE in HCM. Methods We enrolled 244 HCM patients (age=51±15 years, 116 men) studied with vasodilator SE from 1999 to 2019 in 5 certified centers. Stress modality was either adenosine (Ado, 0.14 mg/kg/min in 2', n=171) or dipyridamole (Dip, 0.84 mg/kg in 6', n=73). Left ventricular outflow tract obstruction was present at rest in 80 patients (33%). We assessed CFVR in left anterior descending coronary artery (by TTE in 225, and TEE in 19 patients) and HRR (peak/rest heart rate). Abnormal values of HRR were based on receiver operating characteristics for Ado and Dip separately calculated. All patients completed the follow-up. Results CFVR was 2.17±0.46 for Dip and 2.13±0.43 for Ado (p=ns); HRR was 1.36±0.19 for Dip and 1.10±0.16 for Ado (p&lt;0.001). An abnormal CFVR (&lt;2.0 for both Ado and Dip) was present in 28 patients for Dip and 73 for Ado (38% vs 43%, p=ns). An abnormal HRR (≤1.34 for Dip and ≤1.03 for Ado) was present in 39 patients for Dip and in 70 patients for Ado (53% vs 41%, p=ns). During a median follow-up of 67 months (interquartile range: 29–103 months), 97 spontaneous events occurred in 71 patients: 29 all-cause deaths, 32 new hospital admission for acute heart failure, 3 sustained ventricular tachycardias, 32 atrial fibrillations and 1 heart transplantation. Event rate was 2.5%/year in patients with normal CFVR and HRR, 4.7%/year in patients with only one abnormal criterion and 10.9%/year in patients with abnormal responses of both criteria (see figure). At multivariate analysis, abnormality of both CFVR and HRR (Hazard ratio 4.033, 95% CI 1.863–8.729, p&lt;0.001) was independent predictor of events. Conclusions A reduced CFVR and blunted HRR during vasodilator SE identify distinct phenotypes and show independent value in predicting outcome in HCM patients. Funding Acknowledgement Type of funding sources: None. Figure 1. Kaplan-Meier spontaneous event-free survival curves based on HRR and CFVR. Kaplan-Meier survival curves (considering spontaneous events) in patients stratified with the abnormal HRR and/or CFVR. Number of patients at risk per year is shown.

Abstract Background and Aims Disturbances in calcium-phosphate homeostasis are common after kidney transplantation. The clinical implications of changes in calcium-phosphate homeostasis after transplantation are unclear. The aim of this study was to assess the relationship between time-updated serum calcium and phosphate levels and subsequent graft and patient outcomes. Method Kidney transplant recipients with ≥2 serum calcium and phosphate measurements were included from a large single-center cohort; only first transplants were considered. Patients with graft failure &lt;3 months were excluded, as were measurements obtained when eGFR was &lt;15 mL/min/1.73m2 or during intensive care unit admission. Normocalcemia was defined as (albumin-corrected) calcium between 2.20 and 2.60 mmol/L (8.8-10.4 mg/dL), and normophosphatemia as 0.70-1.50 mmol/L (2.17-4.64 mg/dL). Time-updated multivariable Cox regression analyses and time-updated restricted cubic splines analyses were performed to assess the relationship between post-KTx serum corrected calcium and phosphate levels and mortality and death-censored graft failure (DCGF). Final models were adjusted for recipient age, sex, BMI, eGFR, proteinuria, systolic BP (all time-updated), antihypertensive drug use, recipient CMV status, donor age, sex, and status (living or post-mortal), cold and warm ischemia times, HLA mismatches, primary kidney disease, and serum phosphate (in calcium analyses) or corrected calcium (in phosphate analyses). Results A total of 2,769 patients with 138,496 serum corrected calcium and phosphate levels post-KTx were included (median [IQR] 43 [31-61] measurements per patient). Mean age was 47 ± 14 yrs, 42.3% was female, and 19% underwent a pre-emptive transplantation. Hypercalcemia was more common in the first year (15%) and declined to ∼5% during long-term follow-up; hypocalcemia occurred in ∼10% throughout. Hypophosphatemia (24.3%) and hyperphosphatemia (15.5%) were particularly common during the first 30 days post-transplant, and stabilized at ∼10% and ∼5% after the first year. During median follow-up of 16.3 (8.7 – 25.2) years, 477 patients (17.2%) developed DCGF and 1050 (37.9%) patients died. In multivariable regression analyses, post-transplant hypocalcaemia was associated with an increased risk of DCGF (fully adjusted hazard ratio [HR] 2.01 [95% CI 1.61-2.50], P&lt;0.0001; Figure 1A), but not mortality (HR 1.06 [95% CI 0.88-1.27], P=0.55; Figure 1B). Post-transplant hypercalcaemia was associated with an increased risk of mortality (HR 1.77 [95% CI 1.44-2.17], P&lt;0.0001), but not DCGF (HR 0.79 [95% CI 0.48-1.32], P=0.37). Patients with post-KTx hyperphosphatemia were at increased risk of both DCGF (HR 37.12 [95% CI 30.33-45.42], P&lt;0.0001; Figure 1C) and mortality (HR 3.17 [95% CI 1.65-3.86], P&lt;0.0001; Figure 1D). Patients with hypophosphataemia had a lower risk of developing DCGF (HR 0.48 [95% CI 0.28-0.81], P&lt;0.01), but not mortality (HR 0.92 [95% CI 0.72-1.18], P=0.42). Similar results were obtained in sensitivity analyses in a subgroup with parathyroid hormone data available (N=1,412) or after exclusion of the highest and lowest 0.5% of calcium or phosphate levels. Conclusion Post-transplant hypocalcaemia and hyperphosphatemia are associated with an increased risk of DCGF, while hypophosphataemia was linked with a lower DCGF risk. Hypercalcaemia and hyperphosphataemia were associated with an increased mortality risk. These findings underline the relevance of keeping calcium and phosphate within normal range after kidney transplantation.