Academic literature on the topic '004.728.8, 004.75'

Abstract Objectives To understand how eating behaviors, susceptibility to the food environment, and perceived dietary habit strength differ across self-reported categories of adherence. Methods We used data in a sample (n = 2829) from Adhering to Dietary Approaches for Personal Taste (ADAPT), an online study conducted in self-identified popular diet followers. Adherence was categorized into 3 groups: >95% of the time (high adherers = HA), between 75–95% (moderate adherers = MA); <75% time (lower adherers = LA). The Power of Food Scale (POF) assessed susceptibility to the food environment (availability, presentation, taste), with higher scores indicating food has a higher power over dietary decisions. The Three-Factor Eating Questionnaire captured cognitive restraint (CR), uncontrolled eating (UE), and emotional eating (EE), with higher scores indicating greater response to the specific eating behavior. The Self-Report Habit Index (SRHI) measured perceived habit strength with respect to eating, with a lower score indicating stronger habits. We used ANCOVA adjusting for age, sex, time on diet, and diet group to compare POF, CR, UE, EE, and SRHI outcomes across adherence groups. Results Sixty six percent were HA (n = 1881), 28% MA (n = 787), and 6% LA (n = 161). LA were significantly more susceptible to food availability (mean [95% CI] = 14.9 [13.8–16.1]), presentation (12.1 [11.2–13.1]), and taste (13.4 [12.6–14.2], compared to HA (11 [10.7–11.3], 8 [7.8–8.3],11.6 [11.4–11.9]), respectively. LA indicated significantly greater UE (21 [20.2–21.9]) than HA (17 [16.7–17.4]) and EE (LA = 8 [7.5–8.4] vs. HA = 6.1 [6–6.3]). No significant differences were observed with respect to CR. LA reported weaker SRHI habits (3.4 [3.2–3.6]) compared to HA (1.7 [1.7–1.8]). Differences seen between the LA and MA were similar to those described for HA. Conclusions Our findings show that higher self-reported adherence to dietary patterns is associated with lower susceptibility to negative influences in the food environment, lower uncontrolled and emotional eating, and greater habit strength. Future research should investigate the directionality of the relationship between eating behavior and adherence. Funding Sources USDA Cooperative Agreements 58-8050-9-004 & 58-8050-4-003, General Mills Bell Institute of Health & Nutrition

Abstract Background: Total lymphocyte count (TLC) has been shown to correlate with outcomes in patients (pts) with acute leukemia. The clinical correlation to TLC in pts with chronic myeloid leukemia in chronic phase (CML-CP) who were treated with a tyrosine-kinase inhibitor (TKI) is unclear. Methods: Lymphocyte data in pts with newly diagnosed CML-CP who were enrolled in consecutive or parallel clinical trials with front-line imatinib (IM), nilotinib (Nilo), or dasatinib (Dasa) were collected at the time of diagnosis, and 3 and 6 months (M) after the start of TKI. Relative lymphocytrosis (RLC) was defined as lymphocyte >150% at 3 or 6M compared with baseline at diagnosis. Absolute lymphocytosis (ALC) was defined as lymphocyte > 4,000 /µL at 3 or 6M after the start of TKI. Pts were assessed for response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS) based on ALC and RLC. The Kaplan-Meier method was used to calculate OS, EFS, TFS, and FFS. A log-rank test and Cox regression were used for univariate (UVA) and multivariate analysis (MVA), respectively. Results: A total of 483 pts were enrolled in this study: 271 in IM, 105 in Nilo, and 107 in Dasa. Patient characteristics and outcomes are summarized in Table 1. Median age at diagnosis was 48 years, and median follow-up was 85M and ongoing (5-154+). Time from diagnosis to start of TKI, Sokal risk score, and ALC at baseline between groups did not differ clinically. Of 481 pts, 93 (19%) developed RLC at 3 or 6M; IM, 38 (14%); Nilo, 23 (22%); Dasa, 32 (30%) (p= .001). ALC at 3 or 6M was observed in 15 (3%); IM, 3 (1%); Nilo, 1 (1%); Dasa, 11 (10%) (p<.001). Overall, cumulative incidence of complete cytogenetic response (CCyR) at 6M, major molecular response (MMR) at 12M, molecular response with 4.5 log reduction by IS (MR4.5) at 24M did not differ significantly between RLC and non-RLC (3 or 6M), or between ALC and non-ALC (3 or 6M). 5-y TFS, EFS and OS in ALC group were significantly worse than those in non-ALC group (p= .002, p=.016, p=.008, respectively). By UVA and MVA related to OS, age [p <.001; Hazard ratio (HR), 1.062; 95% confidence interval (95%CI), 1.036-1.089], presence of ALC at 3 or 6M [p = .028; HR, 10.948; 95%CI, 1.297-92.415], absence of MMR at 24M [p=.016; HR, 2.263; 95%CI, 1.165-4.393] were identified as adverse prognostic factors for OS. Conclusion: The presence of ALC ≥4,000/µL at 3 or 6M of TKI therapies is rare but is adversely associated with overall survival. Table 1. Patient Characteristics and Outcomes (N=483)a Overall [n= 481] IM [n= 271] Nilo [n= 105] Dasa [n= 107] Age, (year) 48 (15-85) 48 (15-85) 49 (17-82) 48 (16-83) Sokal Risk, No. (%) Low 334 (69) 175 (65) 79 (75) 80 (75) Intermediate 114 (24) 74 (27) 18 (17) 22 (21) High 32 (7) 20 (7) 8 (8) 4 (4) Time from diagnosis to start of TKI, (M) 0.9 (0-12.6) 1.0 (0-12.6) 0.5 (0-5.6) 0.7 (0.1-7.8) ALC at baseline, (/109L) 2.5 (0-86.6) 2.4 (0-16.7) 2.6 (0.4-9.2) 2.7 (0.3-86.6) Incidence of Relative Lymphocytosis, No. (%) At 3M 65 (14) 25 (9) 16 (15) 24 (22) At 6M 76 (16) 32 (12) 20 (19) 24 (22) Overall 93 (19) 38 (14) 23 (22) 32 (30) Incidence of Absolute Lymphocytosis, No. (%) At 3M 8 (2) 1 (0) 0 7 (7) At 6M 11 (2) 3 (1) 1 (1) 7 (7) Overall 15 (3) 3 (1) 1 (1) 11 (10) Outcomes of RLC and ALC at any time in each group, +/- (%/%) (p) <10% BCR-ABL/ABL at 3M RLC 36/40 (.596) 22/44 (.213) 50/37 (.280) 31/38 (.537) ALC 38/39 (.952) 0/42 (.394) 100/39 (.214) 36/35 (.952) Cumulative CCyR at 6M RLC 75/75 (.288) 50/66 (.063) 96/90 (.413) 90/87 (.628) ALC 67/75 (.711) 33/64 (.276) 0/92 (.001) 82/89 (.599) Cumulative MMR at 12M RLC 67/74 (.406) 53/70 (.030) 83/82 (.921) 72/74 (.903) ALC 60/73 (.488) 33/68 (.197) 0/83 (.033) 73/74 (.745) Cumulative MR4.5 at 24M RLC 46/52 (.564) 37/50 (.139) 57/55 (.889) 50/57 (.729) ALC 33/52 (.332) 33/48 (.610) 0/56 (.264) 36/57 (.252) 5-y FFS RLC 61/71 (.133) 56/69 (.167) 62/70 (.710) 61/74 (.285) ALC 50/69 (.076) 0/68 (<.001) 0/70 (<.001) 71/70 (.974) 5-y TFS RLC 90/93 (.369) 88/93 (.597) 91/88 (.115) 91/99 (.213) ALC 72/93 (.002) 67/93 (.014) 0/90 (<.001) 80/97 (.121) 5-y EFS RLC 80/86 (.213) 71/83 (.154) 84/87 (.450) 86/93 (.486) ALC 64/85 (.016) 33/82 (<.001) 0/87 (<.001) 80/92 (.574) 5-y OS RLC 89/93 (.068) 81/94 (.007) 100/84 (.126) 96/99 (.207) ALC 82/93 (.008) 67/93 (.001) 100/88 (.847) 83/99 (.040) a Two in IM and 1 in Dasa were not evaluable due to lack of differential data at 3 and 6M. Figure 1. OS in Pts with ALC Figure 1. OS in Pts with ALC Disclosures O'Brien: Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding.

Abstract The multicenter CLL2H trial of the GCLLSG evaluated subcutaneous alemtuzumab 3 × 30 mg weekly in fludarabine refractory CLL. From September 2002 to February 2006, 103 patients were enrolled and received at least one dose of alemtuzumab. Median age was 63 (35.1–81.8) years, 72% were male, 74% were Binet C, and a median of 3 (1–10) prior lines had been given. Unfavorable genetics were frequent (17p deletion: 29%, 11q deletion: 19%, unmutated IgVH: 68%, TP53 mutation 34%). Subcutaneous treatment was performed on an outpatient basis in 96% and had to be temporarily interrupted in 65 patients due to neutropenia (27%), anemia (3%), thrombocytopenia (8%), infections (36%), and was stopped early in 65 cases due to insufficient response (43%), hematotoxicity (14%) and infections (29%). The median alemtuzumab dose given was 722 (3–2203) mg. Toxicity during treatment period was mostly grade I/II apart from hematotoxicity. Grade 3/4 neutropenia, thrombocytopenia, anemia occurred in 56%, 57%, and 50% of patients, respectively. Grade 3/4 non-cytomegalovirus infection occurred in 29%. CMV reactivation was observed in 15 % total, Grade 3/4 occurred in 8% of patients. All CMV episodes were successfully treated with anti-CMV therapy, and there was no CMV-related death. Injection site reaction occurred in 34% and was grade 1 or 2 except in 1 patient who had grade 3 reaction. Pegfilgrastim prophylaxis was scheduled for the second half of the trial. Grade 3/4 neutropenia occurred in 70% vs 46% and non-CMV infections occurred in 32% vs 24% in the first and second half, respectively. Development of anti-alemtuzumab antibody was assessed in samples from 21 patients. Plasma anti-alemtuzumab antibody was detectable in only 1 patient, who had a concentration marginally above the detection threshold and was found to be negative in a re-test 5 months later. Stable disease was achieved in this patient. After a median follow-up time of 37.9 months, there were 75 (73%) deaths, 56% due to disease progression, 31% due to infection, and 13% not related to CLL. Overall response rate was 34% (CR 4%, PR 30%), median progression free survival time was 7.7 months, and median overall survival time was 19.1 months. Clinical and biologic parameters (age, sex, B-symptoms, stage, ECOG, number of prior lines, node size, hepato-spenomegaly, WBC, LDH, β2-MG, TK, VH status, genomic aberrations and TP53 mutation) were evaluated for their prognostic role. In univariate analyses, OS was significantly inferior for age &gt; 65 y (12.2 vs 29.0 mo, p&lt;.001), ECOG &gt; 1 (10.8 vs 21.5 mo, p=.011), TK &gt; median (26U/L) (14.9 vs 29.0 mo, p=.001), and β2- MG &gt; 5 (13.6 vs 27.2 mo, p=.004). Median PFS and OS were not different for 17p-, 11q-, other cytogenetic and TP53 mutation subgroups. Multivariate analysis by Cox regression revealed only age (HR 1.6, p&lt;.001) as significant prognostic factor, while TK (p=.11), β2- MG (p=.089), and 17p- (p=.528) showed no significant impact. The choice of next therapy significantly affected survival. Seventy-four patients received subsequent salvage treatment or allogeneic stem cell transplantation (SCT). The median OS since next therapy in these patients was 11.5 months. The 2-year OS rate for allogeneic SCT as compared to other subsequent treatments (chemo-, immuno-, or chemoimmunotherapies) was 86% and 27% (p=0.009).

Abstract Background: Clinical trials report that chemoimmunotherapy with rituximab (R) improves overall survival (OS) and progression-free survival in the treatment (tx) of symptomatic CLL patients (pts). R has been available for first-line CLL tx in BC, population 4.5 million, since 2004. We compared clinical outcomes with and without addition of R to chemotherapy in a large unselected provincial cohort of pts treated for CLL, to determine the "real world" effectiveness of addition of R to standard chemotherapy. Methods: Three large provincial databases (db) were used to identify eligible pts: the BC Provincial CLL db, the BC Lymphoid Cancer db, and the Providence Hematology CLL db. All pts who received minimum 1 cycle of first-line tx for confirmed CLL were included. Pts with > 1 hematologic malignancy (n=8) were excluded. Baseline features of pts treated with (+R) or without R (No R) were compared using Chi-squared for categorical and Kruskal-Wallis test for continuous variables. OS was calculated from date of initial tx to date of death from any cause. Treatment-free survival (TFS) was calculated from date of initial tx to date of next tx/death from any cause. Multivariate analysis (MVA) was performed using Cox proportional hazard models to evaluate the effect of R on OS/TFS, after controlling for covariates including age (³60 yrs vs <60 yrs), Rai stage (3-4 vs 0-2), CD38 status (pos vs neg), presence of 17p (17p-) and 11q (11q-) deletions, and first-line tx with purine analogs (PAs). Results: A total of 1784 pts diagnosed with CLL from 1973-2014 were identified, of which 726 pts (41%) received tx in follow-up. Of treated pts, 393 (54%) received R and 333 (46%) received chemotherapy alone. Among the No R group, tx included: chlorambucil 56%; fludarabine (F) 34%; cyclophosphamide (C)-based 8%; cladrabine 2%. Among the +R group, tx included: FR 75%; C-based + R 17%; FCR 7%; chlorambucil + R 1%. 103 pts underwent bone marrow transplant (BMT) during their tx course (19% No R vs 10% +R, P=.002). Median age at diagnosis (dx) and tx between groups were not statistically different (No R vs +R: 60.6 vs 60.8 yrs and 64.7 vs 63.9 yrs, respectively). There were no clinically significant differences in diagnostic parameters including % with elevated LDH, lymphocyte count >20x109/L , Rai stage 3-4. Median follow-up time in survivors was longer in the No R group (13.0 vs 6.8 yrs, P<.001). Among 467 pts with known CD38 status, CD38 pos was more common in +R vs No R groups (47 vs 36%, P=.02). FISH was performed in 586 pts, with no significant differences in abnormalities between tx groups. Poor-risk FISH, 17p- or 11q-, were present in 29% (No R) and 27% (+R). Median time from dx to initial tx was 2.8 yrs (range 0-20.6) in No R vs 2.5 yrs (range 0-22.7) in +R groups (P=.84). OS was longer in the +R cohort (median OS 11.8 vs 7.1 yrs, P<.001), Fig. 1. Significant improvements in OS were also seen in pts <60 yrs of age at tx (median OS 11.3 vs 3.1 yrs, P<.0001), without 17p- (median OS 9.3 vs 5.2 yrs, P<.0001), and treated with PAs (median OS 9.4 vs 6.4 yrs, P=.0001). Median TFS was longer in pts treated with R (3.3 vs 2.3 yrs, P= .004), Fig. 2, and in those without 17p- (median TFS 3.1 vs 1.3 yrs, P<.001). MVA confirmed that the addition of R to chemotherapy remained a strong independent predictor of mortality (HR 0.66, 95% CI: 0.44-0.98, P=.04) and TFS (HR 0.6, 95% CI: 0.46-0.79, P<.001) after controlling for covariates. Other independent predictors of OS included age ³60 yrs (HR 2.77, 95% CI 1.87-4.10, P<.001) and presence of 17p- (HR 1.23, 95% CI 1.62-3.76, P<.001), whereas for TFS, presence of 17p- (HR 2.08, 95% CI: 1.49-2.91, P<.001) and CD38+ (HR 1.32, 95% CI: 1.03-1.68, P=.025) were independent negative predictors. Conclusion: In this large, population based cohort of pts treated for CLL, we confirm that the addition of R to chemoimmunotherapy as initial tx significantly improves OS, resulting in a 44% lower risk of overall mortality (95% CI, 2% to 66%) after controlling for covariates. We have also demonstrated that the addition of R to first-line therapy significantly delays the time to subsequent therapy, a finding not previously reported in a population based setting to our knowledge. This study complements clinical trial [Hallek, Lancet 2010] and US Registry data [Danese, Blood 2011], demonstrating benefit of the addition of R to standard therapy for first-line treatment of CLL and shows the generalizability of such results in a real world setting. Figure 1 Figure 1. Disclosures Gerrie: Roche: Honoraria, Research Funding. Ramadan:Roche: Honoraria, Research Funding.

Abstract Objectives To evaluate the nutrient adequacy of theoretical, modern-day Paleo meal plans relative to the U.S. Dietary Reference Intakes (DRIs). Methods This analysis used data from the Adhering to Dietary Approaches for Personal Taste (ADAPT) Feasibility Study, which captured data on 9 726 self-reported, popular diet followers. Paleo respondents (N = 925) reported sources of recipes and diet guidance. Five days from each of the top six sources were used to generate 30 days of meal plans among a random sample of n = 200 Paleo respondents. Nutrition Data System for Research (NDSR) was used to estimate daily nutrient content of meal plans which was compared to DRIs and recommendations, as follows: recommended daily allowances (RDAs) for vitamins D, E, and folate, which do not vary by age (years, y)/sex; sex and age-specific RDAs for vitamins A, C, calcium (Ca), magnesium (Mg), and iron (Fe); adequate intakes (AIs) for potassium (K) and fiber; upper intake level (UL) for sodium (Na); and Dietary Guidelines for Americans (DGA) upper threshold to limit saturated fat and Na. Results Estimated daily nutrient intakes of theoretical Paleo meal plans met or exceeded RDAs for the following (Paleo vs. RDA): vitamin A for men or women (1481 RAE µg vs. 900 μg and 700 µg), vitamin D (56 µg vs. 15 μg), vitamin E (27 mg vs. 15 mg), folate (489 µg vs. 400 μg), vitamin C for men or women (225 mg vs. 90 mg and 75 mg), Mg for men and women 31–70 y (539 mg vs. 420 mg and 320 mg), and Fe for men (16 mg vs. 8 mg). Theoretical estimates did not meet the following: RDAs for carbohydrate (91 g vs. 130 g), Fe for women 19–50 y (16 g vs.18 mg), Ca for men and women 61–70 y (562 mg vs. 1000 mg and 1200 mg), and AI for K (4027 mg vs. 4700 mg) or dietary fiber (25 g vs. 28 g/2000 kcal). Estimated levels of Na exceeded the UL (2763 mg vs. 2300 mg), saturated fat exceeded the DGA (19% vs. 10% kcal), and added sugar levels fell within the recommendation (1% vs. 10%). Conclusions While certain aspects of the Paleo diet offer improvements over typical reported intakes of US adults, saturated fat is high, and carbohydrate, fiber, Ca, and K levels of these theoretical diets do not meet DRIs. High levels of saturated fat present concern for cardiovascular health. Optimal nutrition may be challenging to sustain on a Paleo diet. Funding Sources Supported by USDA Cooperative Agreements 58-8050-9-004 and 58-8050-9-003.

Introduction Cytoreduction either with hypomethylating agents (HMA) or induction chemotherapy (IC) before hematopoietic cell transplantation (HCT) for patients with advanced myelodysplastic syndromes (MDS) has been used in an attempt to decrease post-HCT relapse, but the benefit for post-HCT long-term survival remains a debatable issue. We investigated the impact of previous therapy, and depth of response, as well as donor source on the outcome of allo-HCT for patients with advanced MDS. Method After excluding patients who had chronic myelomonocytic leukemia, we analyzed 303 advanced MDS patients (96 (32%) with RAEB-I, 148 (49%) with RAEB-2, and 59 (19%) with tAML) who underwent transplantation from a matched related/unrelated (MSD/URD, n=75/12) or haploidentical (n= 216) donor (HID) after preparation with myeloablative conditioning regimens (identical with BUCY for MSD and BUCY+ATG for HID) between year 2015 and 2018. Results Baseline characteristics Median age was 42 years old. Of the 303, 142 (47%) received only best supportive care (BSC) before HCT; 18 (6%) received IC, 54 (18%) received HMA, and 89 (29%) received both (IC+HMA). Before therapy, 45 (15%), 141 (46%) and 117 (39%) patients had intermediate 1,2 or high-risk scores per the International Prognostic Scoring System (IPSS). Thirty-six (12%) achieved complete remission (CR), 81 (27%) had marrow CR, 160 (53%) had stable disease, and 26 (9%) had progressive disease before HCT defined by International Working Group (IWG). Patients in CR or marrow CR were grouped together as responders (OR) while patients not in CR were grouped together as non-responders (NR) at HCT. Patients had more high-risk disease by WHO and IPSS in the IC and IC+HMA groups. Other patient and donor characteristics known to affect outcomes such as age, time from diagnosis to HCT, IPSS-R, donor source are comparable between groups. Outcome for the entire cohort CR rate at HCT was 6%, 33%, and 30% for HMA, IC, and IC+HMA groups, respectively (P =.001) while OR rate was 37%, 56%, and 70%, respectively (P =.001). With a median follow-up of 727 days, 2-year disease-free survival (DFS) was 77%, 69%,60%, and 62% for BSC, HMA, IC, and IC+HMA groups, respectively (P = .075); 2-y DFS was 77%, 72%,and 56% for untreated, OR, and NR groups, respectively (P = .026); 2-y DFS was 77%, 78%,and 60% for untreated, CR, and non-CR groups, respectively (P = .008); 2-y DFS was 80% and 57% for MSD/URD and HID groups, respectively (P = .051). Multivariate analyses revealed that older age (hazard ratio [HR], 1.03; P< .0001); higher-risk histologic subtypes (HR, 2.3; P =.003), time from diagnosis to HCT (HR,1.005; P =.027), haploidentical donor (HR, 1.9; P =.012) and NR at HCT (HR, 1.6; P =.05) were poor prognostic factors for DFS. Outcome for patients with EB2 and t-AML Focusing on the 207 patients who had BM blasts of 10% or higher before therapy, CR rate at HCT was 6%, 35%, and 33% for HMA, IC, and IC+HMA groups, respectively (P =.007) while OR rate was 44%, 59%, and 74%, respectively (P =.001); 2-year DFS was 77%, 68%,58%, and 62% for BSC, HMA, IC, and IC+HMA groups, respectively (P = .20); 2-y DFS was 77%, 71%,and 50% for untreated, OR, and NR groups, respectively (P = .025); 2-y DFS was 77%, 77%,and 58% for untreated, CR, and non-CR groups, respectively (P = .015); 2-y DFS was 75% and 64% for MSD/URD and HID groups, respectively (P = .43). Propensity score analysis To allow for potential confounding factors between treatments that could influence outcome, a 1:1 ratio propensity score matching was also performed. Included in the propensity score model were: WHO stage, IPSS score, age, time from diagnosis to HCT, and donor source. We were able to pair-match 104 untreated with 104 cytoreductive and 2-y DFS were 80% vs 68% (p= .14); 2-y DFS was 80%, 76%,and 63% for untreated, OR, and NR groups, respectively (P = .19); 2-y DFS was 80%, 94%,and 64% for untreated, CR, and non-CR groups, respectively (P = .015); 2-y DFS was 85% and 68% for MSD/URD and HID groups (P = .044) and the rate was 82% vs 70% after excluding EB-1 (p= .30). After excluding IC group (n=8), 2-year DFS was 80%, 67%, and 75% for BSC, HMA, and IC+HMA groups, respectively (P = .28). Conclusion In this analysis, various therapy approaches before HCT did not lead to different transplantation outcomes. There was no evidence of a benefit in post-HCT outcome associated with prior cytoreductive therapy for advanced MDS. Further randomized studies need to delineate the role of debulking strategy. Disclosures No relevant conflicts of interest to declare.

Abstract INTRODUCTION: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with usually poor prognosis. Age was identified as the independent risk factors in many studies. Elderly patients suffer from comorbidities, impaired organ functions, and poor performance status resulting in worse tolerance of therapy and its efficacy. Data on outcome, prognosis and treatment efficacy for elderly patients with PTCLs are sparse. METHODS: We used data of 941 newly diagnosed PTCLs registered into CLSG database between January 1999 and March 2015 with last follow-up in February 2016. CLSG database covers approximately 85% of all newly diagnosed NonHodgkin´s lymphomas (NHLs) in Czech Republic. For the analysis, 208 patients with age >70 years at diagnosis were selected. RESULTS: Totally, PTCLs accounted for about 8.7% (454/5210) patients of all NHLs in population younger 60 years, but only about 5.8% (208/3561) NHL patients older 70 years. Median age was 76ys (71-91ys), 94 (45%) were women, lactate dehydrogenase (LDH) was elevated in 130/208 (62.5%) pts., ECOG ≥2 had 80 (38%) pts., and advanced clinical stage III-IV presented 132/208 (63.5%) pts. We identified following PTCL subtypes: PTCL-NOS (Peripheral T-cell lymphoma not otherwise specified) 89/208 (43%), Anaplastic large cell lymphoma (ALCL) 34/208 (16.3%), Cutaneous Anaplastic large cell lymphoma (C-ALCL) 10/208 (4.8%), Mycosis fungoides/ Sézary syndrome (MF/SS) together 29/208 (14%), NK/T nasal lymphoma (NK/T) 2/208 (1%), Angioimmunoblastic lymphoma (AITL) 17/208 (8.1%), Cutaneous CD30+ T lymphoproliferative disease 1/208 (0.5%), T-lymphoblastic lymphoma/leukemia (T-LBL) 3/208 (1.4%), T-cell lymphoma without specification (T-NHL) 17/208 (8.1%). Distribution of PTCL subtypes changed significantly with age. There was higher proportion of PTCL-NOS (43% vs. 34%; p.001) and MF/SS (14% vs. 4.8%; p<.001) in elderly patients (>70ys) compared to younger cohort (≤70ys; n=725). Contrary, percentage of ALCL (16.3% vs. 27%; p<.001) with main difference in ALK+ cases (2% vs. 11%; p<.001), and NK/T (1% vs. 5%; p.003) was lower in elderly PTCLs, whereas the incidence of AITL (8.1% vs. 6.6%) or EATL (3.4% vs. 3%) was similar in both age subgroups. For the whole cohort of PTCLs (>70ys), the 5-year overall survival (OS) was 30% and 5-year progression free survival (PFS) was 21% regardless of subtype or stage. Progression is fatal event in elderly patients with median survival about 8 months only. There were significant survival differences between patients (>70ys vs. ≤70ys) according to PTCL subtype; PTCL-NOS 5 yr-OS 23% vs. 43% (p.00001), ALCL ALK+ 5-yr OS not reached vs. 79% (p.01), ALCL ALK- 5 yr-OS 24% vs. 50% (p.001). Patients with AITL or EATL showed no age-related survival differences. First-line chemotherapy was administered in majority of cases (67%); CHOP-like regimen was given in 78 (37%) pts., COP-like in 44 (21%) pts., and other chemotherapy in 18 (9%) cases. Local therapy (surgery, radiotherapy) was administered in first line in 17 (8%) pts., no or palliative therapy (corticoids) was given in 34 (17%) pts., initial therapy was unknown in 17 (8%) cases. We compared two subgroups of patients according to first line chemotherapy CHOP (n=75) vs. COP (n=41). Median age was 74ys (71-84) vs. 79ys (71-89), high IPI was presented in 29% vs. 50% of patients (p.001). Complete response (CR) was achieved in 35/75 (47%) CHOP treated patients, and in 7/41 (17%) patients managed with COP (p.001). Contrary, there were 12/75 (16%) progression in CHOP arm compared to 10/41 (24%) COP treated pts. Five-year OS was 28% vs. 15% better in CHOP group (p.029) and 5-yr PFS 25% vs. 10%, respectively. CONCLUSIONS: In population-based analysis of adult Caucasian PTCL patients, we identified mild decreasing incidence with age. There were significant age-related distribution differences of PTCL subtypes with shift to preponderance of PTCL-NOS, Mycosis fungoides, and NK/T nasal lymphoma in elderly. Worse survival in elderly PTCLs in comparison to younger patients was evident especially for PTCL-NOS and ALCL subtypes. Despite the baseline differences (COP managed pts. had higher IPI), there is tendency that anthracycline-based chemotherapy (CHOP) brings better results with higher proportion of CR and lower progression/relapse rate projected in longer survival. Disclosures Belada: Seattle Genetics: Research Funding. Mayer:AOP Orphan Pharmaceuticals: Research Funding; Novartis: Research Funding.

Abstract Abstract 2987 Acute graft-versus-host disease (GVHD) is a frequent complication after allogeneic bone marrow transplantation (BMT). We previously showed that the adoptive transfer of donor-type CD4+CD25+ regulatory T cells (Treg) at the time of BMT prevents acute GVHD in murine models. However, the therapeutic potential of donor-derived Treg cells for the treatment of established acute GVHD has not yet been examined in detail. In analogy to potential clinical applications we now tested the capacity of in vitro expanded Treg cells to ameliorate acute GVHD after haploidentical BMT (BALB/c→CB6F1). CD4+CD25highCD62L+ Treg cells were purified by FACS and stimulated polyclonally using anti-CD3/CD28-coated beads. Cells expanded on average 130±19-fold (n=7) within 2 wks and maintained high levels of FoxP3 expression (96, 8±0, 8% FoxP3+ cells; n=7) as well as potent immunosuppressive activity in vitro. For the induction of acute GVHD CB6F1 recipients were lethally irradiated and transplanted with 2.5×106 BM cells in combination with 5×106 splenocytes. All animals developed severe GVHD by d11, as revealed by an increase of the GVHD severity score (2.3±0.4 in GVHD animals vs 0±0 in BM controls, p<0.001, n=1–11) and by histological analyses of the gut (score: 7.8±0.4 for the GVHD group vs 0.2±0.2 for BM controls, p =0.046, n=3). When animals with acute GVHD were treated with 5×106 expanded CD4+CD25highCD62L+ Treg cells on d11 after BMT, they initially developed progressive GVHD comparable to non-treated GVHD animals, as indicated by weight loss and an increase of the GVHD score. However from d44 post BMT onwards, Treg-treated GVHD animals regained body weight (d44: 75±3% vs 67±2% of initial weight; p <0.05; n=9–10) and their clinical GVHD score (d44: 6±0 vs 4.3±0.4; p <0.05; n=9–10) decreased. While all non-treated GVHD animals succumbed to disease by d67 after transplantation, 50% of Treg-treated GVHD animals survived for at least 100d (p =0, 002; n=16–21). As immune reconstitution and in particular reconstitution of the lymphocyte compartment is impaired in animals with GVHD, we analyzed the effect of Treg therapy on the reconstitution of the lymphoid and myeloid compartment. At d21 after BMT spleen and BM of non-treated as well as Treg-treated GVHD animals were completely lymphopenic as compared to control mice and both organs contained exceptionally high numbers of granulocytes. Unlike non-treated GVHD animals, however, Treg-treated recipients by d60 showed a recovery of the lymphocyte compartment in spleen (10±2.6×106 T cells and 23.5±12.5×106 B cells in Treg-treated vs 3.0±0.6×106 T cells and 1.5±0.4×106 B cells in non-treated GVHD animals vs 26.25±2.6×106 T cells and 63.9±9.1×106 B cells in BM controls) and BM (0.7±0.1×106 T cells and 8.6±4×106 B cells in Treg-treated vs 0.3±0.01×106 T cells and 0.7±0.4 ×106 B cells in non-treated GVHD animals vs 0.4±0.03×106 T cells and 11.2±0.6×106 B cells in BM controls), while the number of granulocytes decreased constantly. Successful treatment with Treg cells was finally accompanied by a reconstitution of the lymphatic system comparable to control mice. Furthermore, successfully treated mice showed only mild histological signs of gut GVHD at d100 that was significantly lower then those in non-treated GVHD animals with end-stage disease (score: 4.2±1 vs 9.9±1.5 in treated vs non-treated animals, p =0.006, n=4–6). Taken together, these results indicate that in vitro expanded natural Treg cells may not only be effective for the prevention, but also for the treatment of acute GVHD after allogeneic BMT. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction In patients (pts) receiving novel anti-multiple myeloma (MM) therapy, an early marker of response would be useful for predicting patient outcomes. Markers in blood with a short half-life, such as serum free light chain (sFLC), may have the potential to be predictive of early response to treatment. Herein, we report results from a retrospective analysis evaluating the relationship of a reduction in sFLC to best overall response (OR) and progression-free survival (PFS) from 2 phase 2 studies of single-agent carfilzomib (CFZ) in pts with relapsed and/or refractory MM (R/RRMM) (PX-171-003-A1 [003; NCT00511238], median 5 [range 1–20] prior therapies; PX-171-004 [004; NCT00530816], median 2 [range 1–3] prior therapies) and a phase 1/2 study of CFZ, lenalidomide (LEN), and dexamethasone (DEX) (CRd) in pts with relapsed or progressive MM (PX-171-006 [006; NCT00603447], median 2 [range 1–5] prior therapies). Methods Pts in the 003 and 004 studies received CFZ on days (d) 1, 2, 8, 9, 15, and 16 in 28-day cycles. Pts in the 003 study received CFZ at a starting dose of 20 mg/m2 in cycle 1; pts had their dose escalated to a target dose of 27 mg/m2 thereafter for up to 12 cycles. The 004 study included bortezomib (BTZ)-naive and BTZ-treated pts; pts received either CFZ 20 mg/m2 during all cycles or a starting dose of 20 mg/m2 during cycle 1 and a target dose of 27 mg/m2 thereafter. Pts in 006 received CRd in 28-day cycles—CFZ (15–27 mg/m2) on d1, 2, 8, 9, 15, 16; LEN (10–25 mg) orally d1–21; and weekly DEX (40 mg). Responses were assessed by IMWG criteria with minimal response per EBMT criteria on d15 of cycle 1, d1 of cycles 2–12, and at the end of the study. Pts with measurable disease by serum or urine protein electrophoresis were included; pts with disease measurable only by sFLC assay were excluded. An analysis of longitudinal changes in the difference between involved and uninvolved sFLC levels before first evidence of a very good partial response (VGPR) was conducted in pts with k/l <0.26 or >1.65 and involved sFLC ≥50 mg/L. sFLC changes were evaluated using 2 mixed linear models (single-agent: 003 and 004; combination: 006): best OR (≥VGPR vs <VGPR) and time points (d15, 29, 57 of therapy) were the covariates in model 1; PFS (≤6 months, >6 months) and time points (d15, 29, 57) were the covariates in model 2. Correlation between sFLC reduction at d15 and best OR was evaluated using a chi-squared test. Reported P values are 2-sided and with no multiplicity adjustment. Results A total of 221 out of 503 enrolled pts were included in the sFLC analysis. Of these 221 pts, 160 had their sFLC measured at d15. When sFLC changes were assessed in model 1, pts achieving ≥VGPR had greater decreases in sFLC at d15 vs baseline (BL) compared with pts whose best response was <VGPR in both the 003 and 004 populations (P<.0001) and the 006 population (P<.0001). In model 2, pts with PFS >6 months had greater decreases in sFLC from BL vs pts with PFS ≤6 months in 003 and 004 (P<.0001). Pts with PFS >6 months had greater decreases in sFLC from BL vs pts with PFS ≤6 months in 006 study; this change was not significant (P=.1859). Results in Table 1 showed that sFLC decreased significantly more in pts with best OR ≥VGPR than in those with best OR <VGPR at d57 (003), d15 (004) and d15, d29 and d57 (006). In 003, 004, and 006, significantly more pts with a ≥75% reduction in sFLC from BL to d15 achieved ≥VGPR (17/30 [57%]) compared with pts with <75% reduction from BL to d15 (8/130 [6%]; P<.0001) (Table 2). Findings were similar whether pts received single-agent CFZ (003 and 004, P<.0001) or CRd (006, P=.0127). When study groups were compared (003 and 004 vs 006), a significantly greater proportion of pts treated with CRd achieved a ≥75% reduction in sFLC from BL to d15 compared with pts who were treated with single-agent CFZ (45% vs 10%; P<.0001) (Table 3). Conclusions Findings from this retrospective analysis indicate that pts with R/RRMM who are treated with either single-agent CFZ (003, 004) or CRd combination therapy (006), and who exhibit rapid reduction of sFLC levels by d15 of therapy, show a greater predilection for achieving a best response of VGPR or better. A decrease of ≥75% in sFLC from BL on d15 may be associated with increased response (as measured by best OR ≥VGPR) and is more common with CRd than single-agent CFZ. The findings from this analysis—specifically the association of a decline in sFLC at d15—merit further exploration in additional CFZ studies. Disclosures: Vij: BMS: Honoraria; Lilly: Honoraria; Celgene: Research Funding, Speakers Bureau; Onyx: Research Funding, Speakers Bureau; Millenium: Speakers Bureau. Off Label Use: Carfilzomib is a selective proteasome inhibitor that is approved in the US for the treatment of relapsed and refractory multiple myeloma. Wang:Novartis: Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding; Millennium: Research Funding; Celgene: Honoraria, Research Funding; Onyx: Honoraria, Research Funding. Jagannath:Millennium: Honoraria; Celgene: Honoraria; Onyx Pharmaceuticals: Honoraria; Merck: Honoraria; Ortho Biotech: Membership on an entity’s Board of Directors or advisory committees; Imedex: Membership on an entity’s Board of Directors or advisory committees; Medicom WorldWide: Membership on an entity’s Board of Directors or advisory committees; OptumHealth Education: Membership on an entity’s Board of Directors or advisory committees; PER Group: Membership on an entity’s Board of Directors or advisory committees. Niesvizky:Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millennium: The Takeda Oncology Company: Consultancy, Honoraria, Research Funding, Speakers Bureau. Jakubowiak:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Millennium: Consultancy, Honoraria, Research Funding; Onyx: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding; Janssen-Silag: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding. Kavalerchik:Onyx: Employment, Equity Ownership. Huang:Onyx: Employment, Equity Ownership. Siegel:Celgene Corporation: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Millennium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau.