Добірка наукової літератури з теми "Solel Boneh International Group"

Importance Osteoporosis causes increased morbidity and mortality, and thus poses a significant economic burden to the health systems worldwide. Objective The aim of this study was to review and compare the most recently published major guidelines on diagnosis and management of this common medical entity. Evidence Acquisition A thorough comparative review of the most influential guidelines from the RACGP (Royal Australian College of General Practitioners), the ESCEO-IOF (European Society for Clinical and Economic Aspects of Osteoporosis–International Osteoporosis Foundation), the NOGG (National Osteoporosis Guideline Group), the NAMS (North American Menopause Society), the ES (Endocrine Society), and the ACOG (American College of Obstetricians and Gynecologists) was conducted. Results The reviewed guidelines generally agree on the definition, the criteria, and investigations used to diagnose osteoporosis. They also concur regarding the risk factors for osteoporosis and the suggested lifestyle modifications (calcium and vitamin D intake, normal body weight, reduction of alcohol consumption, and smoking cessation). However, there is lack of consensus on indications for fracture risk assessment in the general population and the exact indications for bone mineral density assessment. Referral to a bone specialist is reserved for complex cases of osteoporosis (NOGG, NAMS, and ACOG) or in case of inadequate access to care (RACGP). The use of hip protectors to reduce the risk of fractures is supported by RACGP, NOGG, and NAMS, solely for high-risk elderly patients in residential care settings. All guidelines reviewed recognize the efficacy of the pharmacologic agents (ie, bisphosphonates, denosumab, hormone therapy, and parathyroid hormone analogs). Nonetheless, recommendations regarding monitoring of pharmacotherapy differ, primarily in the case of bisphosphonates. The proposed intervals of repeat bone mineral density testing after initiation of drug therapy are set at 2 years (RACGP), 1–3 years (NAMS, ES, and ACOG), or 3–5 years (ESCEO-IOF and NOGG). All guidelines agree upon the restricted use of bone turnover markers only in bone specialist centers for treatment monitoring purposes. Finally, the definition of treatment failure varies among the reviewed guidelines. Conclusions Osteoporosis is a distressing condition for women, mainly those of postmenopausal age. Thus, it seems of paramount importance to develop consistent international practice protocols for more cost-effective diagnostic and management techniques, in order to improve women's quality of life. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After participating in this activity, the physician should be able to identify early risk factors for osteoporosis; describe the appropriate diagnostic techniques for osteoporosis; and explain available drug agents for the management of osteoporosis, as well as the difference in approach regarding their use.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a clinically defined entity that is recognized by the 2022 International Consensus Classification and the 5 th Edition of the WHO. While the Clonal Hematopoiesis Risk Score (CHRS) incorporates 8 variables that underlie a prognostic framework for prediction of risk for progression to myeloid neoplasm (MN) (Weeks LD et al., NEJM Evidence 2023), there remains debate as to the role of mutations in epigenetic regulators, such as DNMT3A, TET2 and ASXL1 (“DTA”), with respect to clinical outcomes in the real-world setting. Although DTA mutations often occur early in myeloid pathogenesis, the persistence of these mutations as age-related clonal hematopoiesis (CH) might not significantly influence clinical course (Jongen-Lavrencic M et al., NEJM 2018). We have previously observed impaired clearance of DTA-mutant clones with hypomethylating agent or intensive chemotherapy for myelodysplastic neoplasms and acute myeloid leukemia (ASH abstract 4122; Blood (2022) 140 (Supplement 1): 9150-9151), and we now seek to understand the impact of sole DTA mutations in patients with CH. Methods: We studied a pre-selected group of patients who had an indication for undergoing bone marrow evaluation. Such indications included cytopenia(s), elevated blood cell count(s), staging/workup for lymphoma, and radiographic marrow abnormalities. Patients with CH were identified via concurrent morphologic, cytogenetic, and molecular diagnostics of bone marrow aspirates reviewed by UMass and Stanford Hematopathology from 2013 to 2023. CH was defined as presence of a somatic mutation with variant allele frequency (VAF) ≥ 2% on molecular diagnostics or non-myelodysplastic syndrome (MDS)-defining clonal cytogenetic aberration in a patient without morphologic evidence of MN. A total of 79 patients with CH were identified, then segregated based on presence or absence of sole DTA mutations. Results: We assessed the clinical trajectory of patients with CH who did not exclusively have DTA mutations (“non-sole DTA;” n = 58) (Panel A) compared to patients with CH who had DTA mutations alone without any other concurrent mutations (“sole DTA;” n = 21) (Panel B). The median age at detection of CH for sole DTA vs. non-sole DTA was 71.0 ± 2.11 years vs. 71.5 ± 1.45 years, respectively ( p = 0.454). Median number of mutations for sole DTA vs. non-sole DTA patients was 1.24 ± 1.2 vs. 2.24 ± 0.18, respectively ( p < 0.0001). Median follow-up for all patients was 450 days, and the median overall survival was not reached for either group. For non-sole DTA patients, 44 of 58 patients (76%) did not progress, while 14 of 58 patients (24%) progressed to frank MN at the time of analysis. Types of frank MN in the 14 progressors included MDS (50%), MDS/myeloproliferative neoplasm (MPN) overlap (28.6%), AML (14.3%), and MPN (7.1%). For sole DTA patients, 0 of 21 patients (0%) progressed. Regarding distribution of VAFs for sole DTA patients vs. non-sole DTA patients, mean VAF was 13.5% ± 1.91% vs. 31.6% ± 2.18%, respectively ( p < 0.001). For patients with both DTA mutations plus additional mutations, mean VAF for non-progressors vs. progressors was 30.4% ±1.47% vs. 38.6% ± 2.97%, respectively ( p = 0.206). For patients without any DTA mutations but with other somatic mutations, mean VAF for non-progressors vs. progressors was 29.7% ±1.67% vs. 35.2% ± 2.26%, respectively ( p = 0.160). Conclusion: In this study of pre-selected patients with CH, DTA mutations alone were insufficient for progression to frank MN. Progressors included patients with either (1) DTA mutations plus concurrent mutations, or (2) patients without DTA mutations but presence of mutations in other gene clusters. The clinical trajectory of patients with CH in our study differs from that of patients from large consortia possibly because our patients presented with an indication for testing, reflecting real-world data. A limitation of our analysis is the variability in time to recognition and diagnosis of CH, which reflects the high heterogeneity of these patients. Still, our data suggest the need for large-scale studies in the real-world setting to better prognosticate the relevance of DTA mutations for this patient population.

Systemic mastocytosis (SM) is a rare clonal hematologic neoplasm, driven, in almost all cases, by the activating KIT D816V mutation that leads to the growth and accumulation of neoplastic mast cells. While patients with advanced forms of SM have a poor prognosis, the introduction of KIT inhibitors (e.g., midostaurin, and avapritinib) has changed their outlook. Because of the heterogenous nature of advanced SM (advSM), successive iterations of response criteria have tried to capture different dimensions of the disease, including measures of mast cell burden (percentage of bone marrow mast cells and serum tryptase level), and mast cell-related organ damage (referred to as C findings). Historically, response criteria have been anchored to reversion of one or more organ damage finding(s) as a minimal criterion for response. This is a central principle of the Valent criteria, Mayo criteria, and International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria. Irrespective of the response criteria, an ever-present challenge is how to apply response criteria in patients with SM and an associated hematologic neoplasm, where the presence of both diseases complicates assignment of organ damage and adjudication of response. In the context of trials with the selective KIT D816V inhibitor avapritinib, pure pathologic response (PPR) criteria, which rely solely on measures of mast cell burden and exclude consideration of organ damage findings, are being explored as more robust surrogate of overall survival. In addition, the finding that avapritinib can elicit complete molecular responses of KIT D816V allele burden, establishes a new benchmark for advSM and motivates the inclusion of definitions for molecular response in future criteria. Herein, we also outline how the concept of PPR can inform a proposal for new response criteria which use a tiered evaluation of pathologic, molecular, and clinical responses.

Abstract Abstract 2656 Introduction: The International Prognostic Index (IPI) was first developed in 1993 to risk stratify patients with aggressive Non-Hodgkin's lymphoma (NHL) for outcome prediction (Shipp, NEJM, 1993). Since the addition of rituximab to conventional CHOP chemotherapy for the treatment of DLBCL, there have been many efforts to validate the IPI as well as to improve upon the model's capacity to distinguish subgroups with discrete clinical outcomes, especially high-risk patients. Previous studies have focused on adding clinical or biologic prognostic factor(s) to the original model or regrouping the original IPI score (R-IPI; Sehn, Blood, 2007). We, therefore, built anew a modern IPI based solely on clinical factors available in the real world NCCN clinical database. Methods: Using the nationwide population-based NHL lymphoma database from NCCN, patients with newly diagnosed DLBCL enrolled between June 2000 and Dec. 2010 at 7 NCCN cancer centers were included with at least 1 year and up to 5 years of follow-up. Clinical characteristics including age, Ann Arbor stage, ECOG performance status, disease in extranodal sites (including positivity in bone marrow, CNS, liver/GI tract, lung, other sites and spleen), LDH, presence of bulky disease (>10 cm) as well as B symptoms were studied as potential predictors for model development using COX proportional hazards regression. IPI scores were assigned proportionally based on parameter estimates of the statistically significant predictors in the final COX model. Model selection and its comparison to the original IPI model were made based on Akaike Criteria (AIC) and the likelihood ratio test. Categorization of age and LDH was decided by testing the linearity assumption and Martingale residuals. Kaplan-Meier curves were plotted for stratified risk groups per the new and original IPI. Finally, both IPI models were compared using the initial randomly selected 15% validation sample. Results: There were 1,650 DLBCL patients with complete clinical information included for model development. The new IPI model consisted of similar component predictors but used a maximum of 8 scoring points by further categorizing age group into >40–60 (score of 1), >60–75 (score of 2) and >75 yrs (score of 3), and normalized LDH between >1–3 times (score of 1) and 33 times (score of 2) upper limit of normal. These categorizations minimized the Martingale residuals. Age effect was linear and 20-year increments fit the model best, whereas the effect of normalized LDH was not linear and reached plateau at a ratio of 3. Lymphomatous involvement either of bone marrow, CNS, Liver/GI tract or lung appeared as a stronger predictor (p<0.001) than number of extranodal sites (p=0.91). Four risk groups (Low, Low-intermediate, High-intermediate and High) were identified using the current IPI (Table 1) with enhanced discrimination power when compared with the original IPI and better global model fitting statistics, i.e. smaller AIC and significant likelihood ratio test (p<0.001). It was possible to identify a high risk group (score 3 6) with 5-year overall survival of 33% (95% CI: 22%–45%). Better model prediction was also shown in the validation sample. Conclusions: We were able to develop an enhanced IPI model for clinical prediction among previously untreated DLBCL cases by using patient level data from the NCCN NHL database. The NCCN-IPI demonstrates better risk stratification and identifies a poor risk subgroup with <50% 5-year overall survival in the current real-world clinical setting as compared to the original IPI model developed for aggressive lymphoma prior to the rituximab era. Disclosures: No relevant conflicts of interest to declare.

BackgroundPhysipathological mechanisms of spondyloarthritis (SA) are very complex. The role of the interleukin (IL)- 8, which is an angiogenic chemokine, has been suggested [1].ObjectivesWe aimed to evaluate the discriminative value of interleukin 8 in SA.MethodsWe conducted a cross-sectional study during two years (2019-2020) including 144 subjects divided into two groups: a group G1 that included 72 patients followed for spondyloarthritis meeting the Assessement of SpondyloArthritis international Society (ASAS) criteria and a group (G2) including 72 healthy controls. The two groups were matched by age and sex.IL-8 was measured for each participant using chemiluminescence.We performed a ROC analysis and computed the air under the curve (AUC) at IL-8 to assess the ability of this chemokine to diagnose SA and to distinguish between SA patients from healthy controls. Statistical analysis was performed using SPSS.ResultsWe included 57 men and 15 females in each group. The mean age was 44.84 ± 13.42 years. In G1, the mean disease duration was 10.25 ±7.7 years. Axial and peripheral involvements were found in 85% of cases (n=65) and 50% of cases, respectively.The mean BASDAI and ASDAS-CRP were 3.21 ± 1.87 and 2.92 ±1.55, respectively.IL-8 was able to distinguish SA patients from healthy controls with a cutoff of 4.5 pg/mL. The AUC was good at 0.855 (p<0.0001). The sensibility and the specificity were 92.8% and 81.6% (Figure 1).Figure 1.AUC at IL-8 between SA patients and healthy controls 0.855 (p<0.0001)ConclusionSeveral studies have found that IL-8 was significantly higher in SA patients comparing to controls [2,3]. Our study showed that IL-8 could distinguish SA patients from controls with a cutoff of 4.5 pg/mL. This suggests that IL-8 could play a role in the pathophysiology of SA.References[1]König A, Krenn V, Gillitzer R, Glöckner J, Janssen E, Gohlke F, et al. Inflammatory infiltrate and interleukin-8 expression in the synovium of psoriatic arthritis--an immunohistochemical and mRNA analysis. Rheumatol Int. 1997;17(4):159‑68.[2]Limón-Camacho L, Vargas-Rojas MI, Vázquez-Mellado J, Casasola-Vargas J, Moctezuma JF, Burgos-Vargas R, et al. In vivo peripheral blood proinflammatory T cells in patients with ankylosing spondylitis. J Rheumatol. avr 2012;39(4):830‑5.[3]Sonel B, Tutkak H, Düzgün N. Serum levels of IL-1beta, TNF-alpha, IL-8, and acute phase proteins in seronegative spondyloarthropathies. Joint Bone Spine. 1 oct 2002;69(5):463‑7.Disclosure of InterestsNone declared

Abstract Deletion of the long arm of chromosome 5 is the most frequent chromosomal abnormality in MDS (10–15% of MDS cases). Patients with del(5q), particularly those with the ‘5q-syndrome’ have a much better prognosis than other MDS subtypes. Although the presence of additional chromosome abnormalities (ACA), apart from 5q-, has been suggested to negatively influence this favourable outcome, the exact prognostic impact of ACA remains unknown. The aim of the present study was to analyse the prognostic value of ACA in a large series of patients with MDS with 5q- abnormality, treated with supportive care. Three-hundred and five MDS patients with del(5q) were selected from a 3128 cases database that included 1004 patients from the Spanish Haematological Cytogenetics Working Group (GCECGH) (Solé et al., 2005) and 2124 patients from the German-Austrian MDS Study Group (Haase et al., 2007). Patients were separated into two groups: group A (n=204), all del(5q) cases as a single anomaly and group B (n=101) with additional cytogenetic anomalies. Patients in Group B were subdivided according to: the number of additional anomalies (1 to 3 5 anomalies); and the type of additional cytogenetic aberrations: chromosomes 1 and 3, monosomy 7, 7q-, trisomy 8, trisomy 11, trisomy 13, 12p-, involvement of chromosome 17, -18/18q-, 20q-, trisomy 21, loss of X/Y chromosome, and unrelated clones. The series includes 90 males (29.5%) and 215 females (70.5%) with a median age of 66 years (range: 3–92 yr). Using FAB criteria (n=294): 52% had RA, 9% RARS, 30% RAEB, 8% RAEB-t and 1% CMML. WHO classification was available for 217 patients: 52% had ‘5q- syndrome’, 1% RA, 0% RARS, 2% RCMD, 2% RSCMD, 13% RAEB-1, 20% RAEB-2, 1% CMML, 8% AML and 1% were unclassifiable. Overall, 204 (67%) of the patients presented 5q- isolated, 52 (17%) 5q- with one additional abnormality, 10 (3%), 6 (2%), 7 (2%) and 26 (9%) with 2, 3, 4 and 5 or more additional abnormalities, respectively. Follow-up data were available for 273 patients (89.5%). Median survival was 48 months for all. Median survival for patients with isolated del(5q), with one additional abnormality and with two or more additional abnormalities (complex karyotypes) was 69, 55 and 8 months, respectively (P&lt;0.0001). However, no statistical differences were found between patients with isolated del(5q) and patients with only one additional abnormality (P=0.35). Complex karyotypes showed a very adverse outcome. None of the single additional anomalies analysed showed a particular better or worse prognosis. Preliminary results of a multivariate analysis (n=76) showed a highest predictive survival time value for cytogenetics complexity followed by the number of cytopenias and the age. In conclusion, patients with 5q- associated with two or more additional chromosomal abnormalities have a significantly worse overall survival than patients with isolated 5q- or with only one additional anomaly. Our results do not support the exclusion of patients with one single additional chromosomal abnormality and typical bone marrow features from the ‘5q- syndrome’ WHO category. This work is presented on behalf of the Grupo Cooperativo Español de Citogenética Hematológica (GCECGH), German-Austrian MDS Study Group (GASMSG), International Working Group on MDS Cytogenetics of the MDS Foundation.

Abstract Background: Follicular lymphoma (FL) is a heterogenous disease. The optimal timing, sequence and choice of therapy remain matters of debate and there is no optimal prognostic tool. The FLIPI (Follicular Lymphoma International Prognostic Index) is based on five bio-clinical parameters and is widely used, but not as guide for choice of treatment. Recently a new prognostic score (PRIMA-PI), based solely on two parameters, bone marrow involvement and serum beta2 microglobulin (ß2m) was proposed for patients treated with immunochemotherapy (Bachy E., Blood 2018). The Nordic Lymphoma Group (NLG) performed two randomized trials including patients with symptomatic/progressive indolent CD20+ lymphoma, with rituximab monotherapy or rituximab in combination with interferon (IFN)-α2a as primary treatment, without maintenance (Kimby E., 2008, 2015). The 10 years follow-up of these patients showed a good survival with no major safety issues and no need for later chemotherapy in 38% of FL patients (Lockmer S, JCO 2018). Aim/Purpose: To evaluate two different prognostic systems (the new PRIMA-PI and the FLIPI), for overall survival (OS) and time to treatment failure (TTF) in a cohort of symptomatic/progressive FL patients treated with a rituximab-containing first-line regimen without chemotherapy. Methods: Previously untreated patients with a confirmed FL diagnosis (n=269) or indolent lymphoma not otherwise specified (n=22, most FLs with insufficient material for grading), treated in the NLG randomized trials with two cycles rituximab (375 mg/m2 x 4 weeks), with or without IFN-α2a, were classified into the three PRIMA-PI categories: high-risk: ß2m> 3mg / L, intermediate-risk: ß2m ≤ 3 mg / L with bone marrow involvement and low-risk: ß2m ≤ 3 mg / without bone marrow involvement. The FLIPI scores were also assessed. TTF, defined as the interval between randomization and either initiation of new lymphoma therapy due to relapse or intolerance, or death from any cause, as well as OS were estimated using the Kaplan Meier method. The log-rank test was used for comparison between risk groups. Results: Out of 291 patients, 252 had complete data on PRIMA-PI and FLIPI (at the time of randomization in the original trials) and were available for analyses of TTF and OS. Patient characteristics are shown in Table 1. PRIMA-PI seemed to identify a true high-risk group of 47 patients, 32 of them being high risk also according to FLIPI, while a larger patient group (n=117) was classified as FLIPI high-risk. After a long follow-up time, median 9.9 years (0.4 -18.8) from randomization, median 10.6 years for the 214 patients (74%) still alive, 76 patients (26%) were failure-free and 108 (37%) without need of any chemotherapy, Patients with PRIMA-PI high showed a shorter TTF compared to PRIMA-PI intermediate and low (Fig 1a), whereas the FLIPI risk-groups were not significantly separated (Fig 1b). Evidence of transformation to aggressive disease was seen in 55 patients, with no significant difference in frequency between the PRIMA-PI groups, nor between FLIPI groups. Both PRIMA-PI and FLIPI were of significant value for predicting OS, most evident after a long follow-up time (Fig 1c and d). In 41 patients the cause of death was progressive disease or therapy complications, regarded as lymphoma-related death, whereas 21 died of other causes. The lymphoma-specific survival was related to the PRIMA-PI (log-rank p=0.03), but not to the FLIPI (n.s). Prognosis was worse for the PRIMA-PI high-risk group than the for the low-risk, also when adjusted for sex, high age (>60 years), diagnosis, stage, ECOG and FLIPI risk-group; TTF HR 1.82 (95% CI 1.16-2.85, p=0.01) and OS HR 2.3 (95% CI 1.00-5.38, p=0.05). Conclusion: FL patients included in two NLG trials with complete clinical data and a median follow-up of >10 years after randomization have been assessed for validation of different prognostic indices. In these patients, all with chemo-free first-line therapy, the PRIMA-PI was shown a valid predictor of both TTF and OS and seemed more useful than the FLIPI. The PRIMA-PI high risk identified a group of patients (19% of all) with true poor prognosis. Disclosures Kimby: Roche: Honoraria; Roche: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees. Holte:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees; Roche, Norway: Research Funding. Wahlin:Roche: Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Hagberg:Roche: Honoraria.

Abstract Abstract 649 TRM is among the major challenges for the success of HCT. Over the past two decades advances in the prevention and treatment of the major sources of TRM; regimen related toxicity, graft-versus-host disease (GVHD) and infections, have been made. To estimate the combined effect of these advances over time, we assessed changes in the incidence of TRM from 1985 through 2004 in 5,972 patients younger than 50 years, who received bone marrow (BM) or peripheral blood (PB) HCT with myeloablative conditioning for AML in first (CR1) or second (CR2) complete remission reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The incidence of TRM was determined for four consecutive five-year periods for HLA-matched sibling donors (MRD) and the later three for unrelated donor (URD) separately by donor type and disease status at transplant. Cox proportional hazard regression models of TRM and overall survival outcomes were constructed with time periods as the main effect. Adjustments for patient and disease characteristics including age, performance score, coexistent diseases and cytogenetics were made in all multivariate models. Subgroup analyses were performed to account for the influence of major changes in transplant characteristics over time, i.e. GVHD prophylaxis, graft source and HLA matching. We observed a steady drop in the risk of TRM over time among patients in CR1 and CR2 receiving MRD transplants, which was associated with a significant reduction in risk of death (table below). Among URD recipients, TRM also improved with lower RR in 2000-2004 compared to earlier periods. No improvements in long term OS was observed in URD CR1 group. For patients in CR2, the RR for overall mortality was 0.74 (0.6-0.9, p=0.03) for 2000-2004 compared to 1990-1994. Subgroup analyses restricted to recipients of BM grafts, cyclosporine/methotrexate for all transplants and partially HLA-matched grafts for URD resulted in similar trends, suggesting that improvements in TRM were not solely related to utilization of PB, newer GVHD prophylaxis or better HLA matching. In conclusion, our results demonstrate lower risk for TRM over time in patients receiving HCT from MRD and URD for AML in CR1 and CR2. These reductions in risk of TRM have been accompanied by reduced risk of overall mortality in most groups of patients studied. Disclosures: No relevant conflicts of interest to declare.

Abstract An HLA-matched sibling has been considered the optimal donor for allogeneic hematopoietic cell transplantation (HSCT). However, several potential transplant recipients may have a haploidentical sibling or an offspring who may also serve as donors. In this study, we sought to determine the optimal alternative related donor (haploidentical sibling or an offspring) as compared to an HLA-matched sibling. The primary objective was comparison of chronic graft-versus-host disease (GVHD). Secondary outcomes included acute GVHD, non-relapse mortality (NRM), relapse, treatment failure (relapse or death, inverse of relapse-free survival) and overall mortality. The study population included 4540 donor-recipient pairs (n=218 haploidentical sibling; n=218 offspring; n=4104 HLA-matched sibling) with acute myeloid (n=3617) and acute lymphoblastic (n=923) leukemia transplanted in 2008 to 2015. There were few offspring (n=87) who donated to patients aged 18-54 years and haploidentical siblings (n=61) who donated to patients aged 55-76 years and were excluded from the analysis. Post-transplant cyclophosphamide (PT-Cy) with calcineurin inhibitor (CNI) and mycophenolate was used for GVHD prophylaxis for all haploidentical HSCTs. HLA-matched siblings received CNI-containing GVHD prophylaxis; CNI with methotrexate was the predominant prophylaxis regimen. Patient age was correlated with donor age and donor-recipient relationship. Bone marrow was the predominant graft for haploidentical HSCTs (64%) and peripheral blood (89%) for HLA-matched sibling HSCTs. Younger patients (age 18-54 years) of were more likely to receive reduced intensity conditioning regimens for haploidentical HSCTs compared to HLA-matched sibling HSCTs (22%). Among older patients, conditioning regimen intensity did not differ by donor type. Exploratory analysis confirmed differences in survival by patient age. Therefore, based on differences in survival by patient age, two age groups were created: 18 - 54 years and 55 - 76 years and within each patient age group, donor-recipient relationship and its effect on transplant outcomes were tested using Cox regression models. In addition to the standard Cox regression model, we also performed a matched-pair analysis. Recipients of haploidentical HSCT (cases; n=436) were matched to HLA-matched siblings (controls; n=1707) on age, disease and disease risk index. 88% of patients aged 18-54 years were matched to 4 controls and 96% of patients aged 55-76 years were matched to 4 controls. The median difference in age between cases and controls were 0.08 (range 0-9.9) years for patients aged 18-54 years and 0.05 (0 - 9.5) years for patients aged 55-76 years. The results of multivariate Cox regression and matched-pair analysis are shown in Tables 1, 2. Among patients aged 18-54 years, chronic GVHD risks were lower after haploidentical sibling compared to HLA-matched sibling HSCT. There were no differences in acute GVHD, NRM, relapse, treatment failure or overall mortality. Among patients aged 55-76 years, acute and chronic GVHD risks were lower after offspring compared to HLA-matched sibling HSCT. But risks for NRM, treatment failure and overall mortality were higher after offspring compared to HLA-matched sibling HSCT. The 2-year probabilities of overall survival, adjusted for disease risk index and sex are shown in Figure 1. In summary, chronic GVHD rates were lower after haploidentical HSCT with PT-Cy containing GVHD prophylaxis regimens compared to HLA-matched sibling HSCT for all patients. Whether this can be attributed solely to the GVHD prophylaxis regimen or in part attributed to use of peripheral blood grafts for HLA-matched sibling HSCT must be studied further in a setting in which PT-Cy containing GVHD prophylaxis is used for HLA-matched sibling HSCT. Despite lower chronic GVHD with haploidentical sibling donor HSCT with PT-Cy, NRM and overall survival did not differ by donor type for patients aged 18-54 years. However, for patients aged 55 - 76 years, despite lower chronic GVHD with offspring donor HSCT with PT-Cy, NRM was higher and overall survival was lower compared to HLA-matched sibling HSCT. Definitive proof of these findings would require a prospective randomized trial. Disclosures Ciceri: GSK: Other: B-thalassemia gene therapy was developed by Fondazione Telethon and Ospedale San Raffaele and has been inlicenced by GSK that provides funding for the clinical trial, Research Funding. Mohty: Sanofi: Honoraria, Speakers Bureau.

Abstract Introduction: Second-Harmonic Generation microscopy (SHG) has provided progresses in extracellular matrix research, mainly regarding automated analysis of collagen fibers. Nodular sclerosis-classical Hodgkin lymphoma (NS) often has a rich collagen deposition, which remains poorly explored in its biological significance and potential prognostic role. The aim of this study was to characterize the collagen component of NS using SHG, and to investigate its clinical value. Methods: Hematoxylin and eosin stained slides from 53 consecutive samples of paraffin embedded NS tissue were analyzed by SHG imaging in an Inverted Zeiss LSM 780-NLO. HIV-positive individuals were excluded. For comparative purposes, 11 reactive lymph nodes (RL) were also randomly selected. In each slide, 3 capsular areas and 3 sclerotic regions (perinodular septa - PS - in NS and fibrotic foci around germinal centers in RL) were chosen. Collagen near blood vessels was not considered. We evaluated quantity, uniformity and organization of the fibers with ImageJ and OrientationJ plug-in in 4 hotspots from each image. Shapiro-Wilk test was used to assess data normality, while t-tests and Pearson correlations were performed to analyze collagen parameters between two groups. Overall survival (OS) was defined as time from diagnosis until death from the disease or last follow-up. Event-free survival (EFS) was set as time from diagnosis until progressive disease, death from the disease or last follow-up. Collagen data were used in survival analyses as continuous variables (in Cox-hazards model) or categorical ones (by choosing the mean value as a threshold for Kaplan-Meier curves and log-rank test). Significance was set at p<0.05. Results: NS patients were mostly female (58.5%). The mean and median values of age at diagnosis were, respectively, 33 and 29 years (range: 14-82 years). Forty-two patients (79.2%) had B-symptoms, while bulky disease was seen in 23 cases (43.3%). Bone marrow was infiltrated in 4 patients (7.5%). Based on the International Prognostic Score (IPS), patients were stratified as follows: 39 (73.5%) as low-risk (IPS ≤ 3) and 14 (26.5%) as high-risk (IPS > 3). The first-line treatment was ABVD in 40 cases (75.5%) and BEACOPP in 13 patients (24.5%). Radiotherapy was performed in 27 (50.9%) patients. Tumor PS presented more dense (p<0.01), organized (p<0.01) and uniform (p=0.02) fibers than sclerosis in RL. NS capsule had only a more organized collagen than RL (p=0.02). Considering solely NS, we found significant correlations of collagen fibers quantity (r=0.67), uniformity (r=0.78) and organization (r=0.49) between capsule and PS, suggesting a proportional deposition of collagen in these compartments. When clinical data were analyzed in the entire patient group, the presence of more organized PS collagen was associated with low-risk IPS (p=0.03), grade 2 tumors (p= 0.04), extranodal disease (p=0.003) and a higher risk of death (p=0.02). On the other hand, a higher fiber organization in NS capsule was only associated with low-risk IPS (p=0.03). The presence of high-risk IPS was associated with a shorter EFS (p=0.002), but had no relationship to OS. Collagen parameters had no impact on EFS. However, in univariate Cox regression, higher collagen quantity (p=0.04) in PS was the only factor associated with a worse OS. When only high-risk IPS cases were analyzed in Cox regression model, PS collagen had association with unfavorable OS regarding higher collagen quantity (p=0.03) and uniformity (p<0.01). In this setting, a higher quantity of capsular collagen was also associated with a worse OS (p=0.02). We did not perform multivariate analysis in this group due to the small amount of patients (14). Also in the high-risk cases, using the mean value of PS collagen quantity (15.19) as a threshold to binarize data, we found a trend to worse OS in cases with a higher collagen quantity (p=0.05, figure 1). Considering only low-risk IPS cases, collagen factors had no association with OS. Conclusion: Collagen parameters in NS have distinct features than in RL and affect clinical presentation of the tumor. Moreover, collagen quantity and uniformity in cases with high-risk IPS were associated with survival, which indicates that incorporation of collagen information might be relevant in the prognostication of NS. Figure 1. Survival curve of high-risk patients (n=14) stratified according to the perinodular collagen (pCOL) quantity threshold. Figure 1. Survival curve of high-risk patients (n=14) stratified according to the perinodular collagen (pCOL) quantity threshold. Disclosures No relevant conflicts of interest to declare.