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Introduction: High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) may provide survival benefit in patients with non-hodgkin lymphoma (NHL). Retrospective analyses suggest that the benefit of HDT extends to elderly patients with NHL, which is an important finding considering that the median age at diagnosis is 67 years (range: 65-74) for NHL in United States, using 2010-2014 US SEER data. We aimed to define the efficacy and toxicity of AHCT in patients >60 years with NHL. Patients and Methods: From January 2005 through January 2021, data from 36 patients with aggressive NHL above 60 years of age who were eligible for AHCT according to geriatric assessment (GA) were evaluated. Their diagnoses were as following; 21 diffuse large B cell lymphoma (primary refractory or relapsed disease), 11 mantle cell lymphoma (first complete remission), 2 follicular lymphoma, 1 peripheral T cell lymphoma and 1 anaplastic large cell lymphoma. We compared the toxicity profile and outcome between the research group: patient aged 60 years and above and the control group: patient Results: All of the patients were stage III or IV at diagnosis; ten out of 36 elderly patients had active disease at the time of AHCT. The median follow-up was 20.5 months (range, 1-60 mos). Prior to transplantation majority (85%) of the elderly patients received BEAM protocol as conditioning treatment. Bone marrow stem cell was used in only 1 patient None of the patient had mobilization failure, the median peripheral CD34 level was 5.24x10 6/kg. Forty-eight percent of the patients experienced grade 3-4 mucositis and 77% of the patients had microbiology-documented infection. Sixty-two percent of the patients had diarrhea with median duration of 8 days (range, 5-20 days). Renal toxicity was occurred in 7 (27%) patients while hepatic toxicity in 1(10%) patients. Median time to neutrophil recovery was 10 days (range, 8-18 days) and platelet recovery 11 days (range, 10-32 days). Overall response was obtained from all patients (23% CR). At the time of data collection, 7 patients (19.4%) of patients' ≥ 60 years have deceased. Relapse (n=3) was the main course of death. The probability of 4-year progression free survival (PFS) and estimated overall survival (OS) in elderly patients were 44.4% and 39.4%, respectively. Conclusion: Based on this single center study, AHCT is safe and efficacious in the treatment of elderly lymphoma patients. We emphasize the need for further research in order to determine the risk-benefit threshold for stem cell transplantation based on age coupled with comorbidity and fragility. Disclosures Özcan: Bayer: Research Funding; Archigen: Research Funding; Amgen: Honoraria, Other: Travel/Accommodations/Expenses; Janssen: Other: Travel/Accommodations/Expenses, Research Funding; Roche: Other: Travel/Accommodations/Expenses, Research Funding; Celgene: Research Funding; MSD: Research Funding; Abbvie: Other: Travel/Accommodations/Expenses, Research Funding; AstraZeneca: Research Funding; Takeda: Honoraria, Other: Travel/Accommodations/Expenses, Research Funding; Pfizer: Research Funding; BMS: Other: Travel/Accommodations/Expenses; Jazz: Other: Travel/Accommodations/Expenses; Sanofi: Other: Travel/Accommodations/Expenses; Abdi Ibrahim: Other: Travel/Accommodations/Expenses. Beksac: Amgen,Celgene,Janssen,Takeda,Oncopeptides,Sanofi: Consultancy, Speakers Bureau.

Introduction: Post-induction minimal residual disease (MRD) within but not outside (peripheral blood/stem cell graft) of marrow among transplant eligible patients with multiple myeloma (MM) is currently recognized as poor-prognostic. Emerging number of studies are evaluating MRD within the context of cytogenetic risk. In this study we aimed to quantify circulating plasma cells (PCs) by flow in apheresis products (graft=gMRD) and compare with marrow MRD(mMRD) and outcome according to cytogenetics. Patients & Methods: Four hundred eleven subsequent newly diagnosed multiple myeloma (NDMM) patients transplanted (AHCT) between September 2006 - June 2021 were included prospectively. Standard-risk cytogenetics(SR) is defined as t(11;14), t(6;14), or a normal karyotype , whereas del(17p13), t(4;14), t(14;16), t(14;20), + 1q21 and complex findings are high-risk cytogenetics (HR). In the sample drawn for HPSC quantification of the graft and bone marrow, the number of clonal PCs were quantified by Flow. CD27 PC7 orCD27 A750, CD56 A700, CD19 ECD, CD38 FITC orCD38 A750, CD138 APC, CD45 KO, CD81 PE, CD117 PC7, polyclonal Rabbit Anti-Human Kappa or Lambda Chains /FITC antibodies and acquisition of at least 10 5 cells per tube Analysis was performed using the Navios Flow Cytometer (3L10C, Beckman Coulter) using the Kaluza software (Beckman Coulter, USA) according to the criteria defined by Montero et al and also abnormal distribution of kappa vs. Lambda expression. Undetectable MRD was defined as absence of clonal PCs at a sensitivity of 10 -4 prior to 2017(n=217) and 10 -5 after 2017(n=131). MRD assessment is similar in the graft and marrow. Impact of postinduction MRD analysis was performed in 131 patients with MRD data of 10 -5 sensitivity level. Results were reported in the intention-to-treat (ITT) population for mMRD. Results: Median follow-up after AHCT was 61.5 months (range:3.2-168) (prior to 2017) and 17.7 months (range: 3-47.4) (after 2017). Induction regimen consisted of bortezomib without or with immunomodulatory drug (IMID) 78.8%, 2.8% (prior to 2017) and 74.1%, 22.9% (after 2017). Consolidation 18% (n=39/217), 22.1% (n=29/131) (prior and after 2017) and maintenance 21.2% (n=46/217), 35.1% (n=46/131) (prior and after 2017) were administered based on the response to AHCT. Cytogenetically HR was observed 14.1% (n=47) (among total cohort) and 15.8% (n=19) (after 2017 cohort). Post-induction biochemical response distribution among patients with undetectable MRD are shown in Table-1. MRD assessments were performed at a sensitivity of 10 -4 and 10 -5 in graft (n=147 and 76), marrow (n=18 and 4) or both (n=52 and 51). A statistically significant correlation was detected between marrow and graft MRD only at sensitivity level 10 -5 (SE: 0.638, p Conclusion: Our real-world triplet drug induction-based experience shows for the first-time post-induction mMRD and MRD to be correlated with each other and with PFS. PFS with MRD(-) at 10 -5 results have displayed a better outcome compared to 10 -4. MVA showed MRD and age to determine PFS, independent from post-induction CR, ISS and cytogenetic risk. Although observed less frequently, achieving post-induction MRD(-) either in graft or marrow may ameliorate the poor prognosis of HR. With improvement in induction it may be possible to achieve more frequent MRD(-) and thus analyze the impact of each cytogenetics risk group ie 1q amplification separately. Furthermore, MRD in graft may be a non-invasive therapeutic efficacy tool which is subject to less sampling variation. Figure 1 Figure 1. Disclosures Beksac: Amgen,Celgene,Janssen,Takeda,Oncopeptides,Sanofi: Consultancy, Speakers Bureau.

Background:Waldenström Macroglobulinemia (WM) remains an incurable disease with a heterogeneous course, relapse following initial treatment happens in virtually all patients. Ibrutinib, a Bruton Tyrosine Kinase inhibitor, is a promising drug used in WM, chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and chronic graft versus host disease. Ibrutinib first received FDA approval in WM as a monotherapy in January 2015 and expanded the approved use of ibrutinib with rituximab in August 2018.Ibrutinib-related prior data in Waldenström Macroglobulinemia (WM) remain sparse, particularly outside of clinical trials. Herein, we share a real-life experience using off-label ibrutinib in the treatment of heavily pretreated WM. Methods:This multicenter retrospective study conducted in eight different sites included 13 adult patients diagnosed with WM and used off-label ibrutinib monotherapy or with rituximab from April 2016 to November 2019. Disease-refractoriness to prior therapy was defined as progression on therapy or within 2 months of treatment interruption. The response rates were assessed by the modified Third International Workshop on WM Response Criteria. Results:TwelveRRWM patients received ibrutinib monotherapy for active/symptomatic WM during the study period; median follow up of the entire cohort was 29 months for the subset that received ibrutinib as salvage therapy. The median time on therapy for the entire cohort was 12.5 months. WM IPSS score was calculated intermediate in three patients and high in nine patients. MYD88 mutation status was assessed in five patients and detected positive at the time of WM diagnose. Before therapy, six of the 12 (50%) had a serum level of 3000 mg per deciliter or higher; after treatment, at the time of best response, two of the 12 patients (16.6%) had a serum IgM level of 3000 mg per deciliter or higher. ECOG performance score was 1 in 75% of our cohort. The median lines of prior therapy for the RRWM were 3 (range: 2-8). Only two patients had received autologous stem cell transplantation (ASCT) prior to ibrutinib monotherapy. Responses included a complete response in three patients, a very good response in 1 patient and a partial response in six patients, representing overall response of 83.3%. The remaining two patients discontinued ibrutinib due to progressive disease. No several adverse events due to ibrutinib were observed in our cohort. At the time of data collection, one patient had deceased. Conclusion:Ibrutinib is an effective drug, associated with durable responses, and safety for both previously-treated and newly diagnosed WM. Our study has several limitations that should be considered when reviewing the results, including the retrospective design and inclusion of a small number of patients. Nevertheless, because of the rarity of the diseases, our data provide useful information on the use of ibrutinib in patients with heavily pretreated WM. Disclosures Ferhanoglu: Janssen: Other: Advisory Board; Roche: Other: Advisory Board; Abbvie: Other: Advisory Board; Takeda: Other: Advisory Board. Beksac:Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen&janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Deva: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: ibrutinib were used off-label

Introduction: MDS is associated with an erythroid maturation defect, characterized by ineffective erythropoiesis leading to anemia and RBC transfusion dependence. Treatment of anemia in lower-risk MDS remains an unmet medical need. Luspatercept is a first-in-class erythroid maturation agent which binds to select TGFβ superfamily ligands to reduce aberrant Smad2/3 signaling and enhance late-stage erythropoiesis (Suragani RN, et al. Nat Med. 2014;20:408-14). Preliminary clinical studies have shown promising activity in MDS (Platzbecker U, et al. Lancet Oncol. 2017;10:1338-47). We report the results of a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of luspatercept in patients with anemia due to Revised International Prognostic Scoring System (IPSS-R)-defined Very low-, Low-, or Intermediate-risk MDS with RS who require RBC transfusions. ClinicalTrials.gov identifier: NCT02631070. Methods: Eligible patients were aged ≥ 18 years; had IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS with RS according to the WHO 2016 criteria; were refractory, intolerant, or ineligible to receive erythropoiesis-stimulating agents (ESAs); and required RBC transfusions. Patients were randomized 2:1 to receive either luspatercept, at a starting dose level of 1.0 mg/kg with titration up to 1.75 mg/kg, if needed, or placebo, subcutaneously every 3 weeks for ≥ 24 weeks. The primary endpoint was RBC transfusion independence (RBC-TI) for ≥ 8 weeks between week 1 and week 24. A key secondary endpoint was RBC-TI for ≥ 12 weeks between week 1 and 24. Achievement of modified hematologic improvement-erythroid (mHI-E) response using IWG 2006 criteria was also assessed. Results: † A total of 229 patients were randomized and treated. Median age was 71 years (range 26-95), median time from diagnosis was 41.8 months (range 3-421), and 62.9% were male. Overall, patient baseline characteristics were balanced between the treatment groups. Patients received a median of 5 RBC units (range 1-20) transfused over 8 weeks during the 16 weeks prior to treatment (43.2% of patients had ≥ 6 RBC units/8 weeks, 27.9% had ≥ 4 to < 6 RBC units/8 weeks, and 28.8% had < 4 RBC units/8 weeks). At baseline, 138 (60.3%), 58 (25.3%), and 32 (14.0%) patients had serum erythropoietin levels < 200 IU/L, 200-500 IU/L, and > 500 IU/L, respectively. A total of 218 (95.2%) patients had previously received ESAs. Overall, 206 (90.0%) patients had an SF3B1 mutation. Of 153 patients receiving luspatercept, 58 (37.9%) achieved the primary endpoint of RBC-TI for ≥ 8 weeks compared with 10 of 76 patients (13.2%) receiving placebo (odds ratio [OR] 5.1, P < 0.0001). Of those receiving luspatercept, 43 of 153 (28.1%) achieved the key secondary endpoint of RBC-TI for ≥ 12 weeks (weeks 1-24) compared with 6 of 76 (7.9%) receiving placebo (OR 5.1, P = 0.0002). Patients receiving luspatercept were more likely to achieve an mHI-E response, defined as a reduction in transfusion of ≥ 4 RBC units/8 weeks or a mean hemoglobin increase of ≥ 1.5 g/dL/8 weeks in the absence of transfusions, compared with patients receiving placebo (52.9% vs 11.8% during weeks 1-24; P < 0.0001). The safety profile of luspatercept was consistent with that reported in the phase 2 PACE-MDS study (Platzbecker U, et al. Lancet Oncol. 2017;10:1338-47). Conclusions: Treatment with luspatercept resulted in a significantly reduced transfusion burden compared with placebo in patients with anemia due to IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS with RS, who require RBC transfusions, and was generally well tolerated. P.F. and U.P. contributed equally to this abstract as lead co-authors. R.S.K. and A.F.L. contributed equally to this abstract as senior co-authors. † As of May 8, 2018, cutoff date. Disclosures Fenaux: Otsuka: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Platzbecker:Celgene: Research Funding. Mufti:Celgene: Research Funding. Buckstein:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Santini:Otsuka: Consultancy; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding; Novartis: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Díez-Campelo:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Finelli:Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Celgene: Research Funding, Speakers Bureau. Ilhan:Alexion: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Celgene: Speakers Bureau. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Falantes:Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Giai:Novartis: Consultancy; Pfizer: Consultancy. Selleslag:Kiadis Pharma: Other: Financial support for study-related issues. Jurcic:Actinium Pharmaceuticals, Inc: Research Funding; Daiichi-Sankyo: Research Funding; Astellas: Research Funding; Incyte: Consultancy; AbbVie: Consultancy, Research Funding; Kura Oncology: Research Funding; Genetech: Research Funding; Celgene: Research Funding; Forma Therapeutics: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Syros Pharmaceuticals: Research Funding. Germing:Novartis: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria, Research Funding. Götze:Takeda: Honoraria, Other: Travel aid ASH 2017; Celgene: Honoraria, Research Funding; Novartis: Honoraria; JAZZ Pharmaceuticals: Honoraria. Quesnel:Celyad: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Sunesis: Honoraria. Beyne-Rauzy:Novartis: Research Funding. Cluzeau:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Consultancy; Pfizer: Speakers Bureau. Voso:Celgene: Research Funding, Speakers Bureau. Zeidan:Otsuka: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Agios: Consultancy, Honoraria. Laadem:Celgene: Employment, Equity Ownership. Benzohra:Celgene: Employment, Equity Ownership. Zhang:Celgene: Employment, Equity Ownership. Rampersad:Celgene: Employment, Equity Ownership. Linde:AbbVie: Equity Ownership; Abbott Laboratories: Equity Ownership; Fibrogen: Equity Ownership; Acceleron Pharma: Employment, Equity Ownership. Sherman:Acceleron Pharma: Employment, Equity Ownership. Komrokji:Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding. List:Celgene: Research Funding.

61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) -- DEC 07-10, 2019 -- Orlando, FL, BERBER, Ilhami/0000-0003-3312-8476, WOS:000577164606194, [No Abstract Available], Amer Soc Hematol

Introduction: Lower-risk MDS is characterized by anemia and ineffective erythropoiesis leading to RBC transfusion dependence. Effective treatment for anemia remains an unmet medical need. Patients with MDS may also experience additional cytopenias that may complicate treatment and contribute to infections and bleeding events. Here, we report hematologic improvement (HI) outcomes for patients in the MEDALIST trial (ClinicalTrials.gov identifier: NCT02631070), a phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of luspatercept, a first-in-class erythroid maturation agent that binds select TGF-β superfamily ligands to reduce aberrant Smad2/3 signaling and enhance late-stage erythropoiesis. Methods: Eligible patients in the MEDALIST trial were adults with anemia due to Very low-, Low-, or Intermediate-risk MDS with RS according to the Revised International Prognostic Scoring System; were refractory, intolerant, or ineligible to receive erythropoiesis-stimulating agents (ESAs); and required RBC transfusions. Patients received luspatercept (starting dose of 1.0 mg/kg and titration up to 1.75 mg/kg, if needed) or placebo subcutaneously every 3 weeks for ≥ 24 weeks. Platelet and neutrophil counts were assessed by the central laboratory. Secondary endpoints included HI-neutrophil (HI-N) and -platelet (HI-P) responses, using International Working Group 2006 criteria, over any consecutive 56-day period. Mean changes from baseline in platelets and neutrophils were also evaluated. Results*: A total of 94.8% patients in the luspatercept arm and 97.4% in the placebo arm had refractory cytopenia with multilineage dysplasia and RS at baseline. Mean neutrophil and platelet counts at baseline for patients in the luspatercept arm were 2.8 x 109/L and 259 x 109/L, respectively, and in the placebo arm were 2.7 x 109/L and 252 x 109/L, respectively. Neutropenia (< 1 x 109/L) was confirmed at baseline in 15 (9.8%) and 10 (13.2%) patients in the luspatercept and placebo arms, respectively. Fifty-one (33.3%) patients in the luspatercept arm and 22 (28.9%) in the placebo arm received granulocyte colony-stimulating factor in combination with ESAs prior to randomization. A total of 8 (5.2%) and 6 (7.9%) patients receiving luspatercept and placebo, respectively, had baseline thrombocytopenia (< 100 x 109/L); no patients received prior platelet transfusions. Fifteen (9.8%) and 10 (13.2%) patients in the luspatercept and placebo arms, respectively, were evaluable for HI-N (i.e. baseline neutrophils < 1 x 109/L); 3/15 (20%) of those receiving luspatercept and 1/10 (10%) of those receiving placebo achieved HI-N in Weeks 1-48. Among patients who were evaluable for HI-P (i.e. baseline platelets < 100 x 109/L), 5/8 (62.5%) of those receiving luspatercept and 2/6 (33%) of those receiving placebo achieved HI-P in Weeks 1-48 (Table). None of the luspatercept HI-P responders received platelet transfusions. Mean changes from baseline in neutrophils of 0.94 x 109/L with luspatercept and 0.04 x 109/L with placebo were observed at Week 15, with early increases reported for luspatercept by Day 8 (0.86 vs 0.08 x 109/L for placebo). Mean increases in neutrophils at Day 8 occurred in both luspatercept responders (by MEDALIST primary endpoint; 1.0 x 109/L) and non-responders (0.8 x 109/L). Mean changes from baseline in platelets of 29 x 109/L were observed with luspatercept and 0.9 x 109/L with placebo by Week 12, but early increases were observed with luspatercept by Day 8 (18 vs 3 x 109/L for placebo) and mean increases in platelets at Day 8 occurred in both luspatercept responders (21.4 x 109/L) and non-responders (16.5 x 109/L). No patients in either arm experienced grade 3 or 4 treatment-emergent thrombocytopenia. Treatment-related grade 3 or 4 neutropenia was reported in 1 (0.7%) patient receiving luspatercept and 1 (1.3%) patient receiving placebo. Conclusions: Although only a minority of patients were evaluable for HI-P/HI-N response based on entry criteria for the study, luspatercept treatment resulted in a mean increase from baseline in platelet and neutrophil counts in most patients overall vs placebo, regardless of response status. These improvements were observed early following treatment initiation and then stabilized. Luspatercept did not contribute to the worsening of cytopenias vs placebo. *Data cutoff: May 8, 2018. Disclosures Garcia-Manero: Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Mufti:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cellectis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Fenaux:Celgene Corporation: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Aprea: Research Funding. Buckstein:Takeda: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Santini:Acceleron: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria. Díez-Campelo:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Finelli:Celgene Corporation: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. List:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Laadem:Celgene Corporation: Employment, Equity Ownership. Ito:Celgene Corporation: Employment, Equity Ownership. Zhang:Celgene Corporation: Employment, Equity Ownership. Rampersad:Celgene Corp: Employment, Equity Ownership. Sinsimer:Celgene Corporation: Employment, Equity Ownership. Linde:Fibrogen, Inc.: Equity Ownership; Abbott Laboratories, Inc.: Equity Ownership; Acceleron Pharma: Employment, Equity Ownership. Platzbecker:Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Komrokji:Alexion: Speakers Bureau; Incyte: Consultancy; Janssen: Consultancy; Agios: Consultancy; Celgene: Consultancy; Pfizer: Consultancy; Jazz: Speakers Bureau; DSI: Consultancy; Novartis: Speakers Bureau. OffLabel Disclosure: Luspatercept is an investigational therapy that is not approved for any use in any country. Luspatercept is currently being evaluated for potential use in patients with anemia due to myelodysplastic syndromes, beta-thalassemia, or myelofibrosis.

Introduction: Few treatment options are available to RBC transfusion-dependent pts with lower-risk MDS (LR-MDS) who are refractory/ineligible for erythropoiesis-stimulating agents (ESAs). Luspatercept is a first-in-class erythroid maturation agent that binds select TGF-β superfamily ligands to reduce aberrant Smad2/3 signaling and enhance late-stage erythropoiesis. In the phase 3, randomized, double-blind, placebo-controlled MEDALIST study (NCT02631070), luspatercept significantly reduced transfusion burden vs placebo. Longer-term efficacy analyses of the MEDALIST study (data cutoff Jan 7, 2019), including multiple responses, and safety are presented here. Methods: Eligible pts were ≥ 18 years of age with IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS with RS (World Health Organization 2016 criteria); were refractory, intolerant, or unlikely to respond to ESAs (serum erythropoietin > 200 U/L); and required regular RBC transfusions. Pts were randomized 2:1 to luspatercept (1.0 mg/kg titrated up to 1.75 mg/kg, if needed) or placebo, subcutaneously every 3 weeks (wks). This analysis assessed the achievement and number of individual response periods of RBC transfusion independence (RBC-TI) ≥ 8 wks. Clinical benefit, defined as achieving RBC-TI ≥ 8 wks and/or modified hematologic improvement-erythroid (HI-E) response per International Working Group 2006 criteria, was also assessed, along with total duration of clinical benefit (time from achieving clinical benefit to discontinuation due to loss of benefit, adverse events [AEs], or other reasons). Longer-term efficacy and safety were also evaluated. Results: Pts were assessed for RBC transfusion burden/8 wks in the 16 wks before randomization: 66 pts received 2 to < 4 U RBCs (30.1% and 26.3% of pts receiving luspatercept and placebo, respectively), 64 received ≥ 4 to < 6 U (26.8% and 30.2%, respectively), and 99 received ≥ 6 U (43.1% and 43.4%, respectively); both arms had a median baseline burden of 5 RBC U/8 wks. Compared with our previous analysis and earlier data cutoff of May 8, 2018 (Fenaux P, et al. Blood. 2018;132:1), we now report that as of Jan 7, 2019, 72 (47.1%) pts treated with luspatercept and 12 (15.8%) treated with placebo achieved RBC-TI ≥ 8 wks. Analysis of multiple response periods of RBC-TI ≥ 8 wks in the luspatercept responders (i.e. initial RBC-TI ≥ 8 wks, followed by transfusion, followed by another period of RBC-TI ≥ 8 wks) demonstrated that 48 (66.7%) pts had ≥ 2 separate response periods, 22 (30.6%) had ≥ 3, 12 (16.7%) had ≥ 4 , and 7 (9.7%) had ≥ 5. Of the 12 pts achieving RBC-TI ≥ 8 wks with placebo, 4 (33.3%) had ≥ 2 responses; none had > 3. Overall, 48 (31.4%) pts receiving luspatercept and none receiving placebo remained on treatment as of the Jan 7, 2019 data cutoff. Median treatment duration was 50.9 (range 5.9-147.0) wks in pts receiving luspatercept vs 24.0 (range 7.4-103.0) wks in pts receiving placebo. Median duration of the longest period of RBC-TI ≥ 8 wks during Wks 1-48 was 30.6 (95% confidence interval [CI] 20.6-50.9) wks with luspatercept and 18.6 (95% CI 10.9-not evaluable) wks with placebo. Median total duration of clinical benefit was 83.6 and 26.8 wks for pts responding to luspatercept (n = 97) and placebo (n = 20), respectively. Of the 97 luspatercept-treated pts evaluable for clinical benefit, median duration of clinical benefit in pts with baseline transfusion burden of 4 to < 6 U/8 wks was 87.9 (range 13-125) wks, of < 4 U/8 wks was 84.7 (range 21-147) wks, and of ≥ 6 U/8 wks was 64.9 (range 8-122) wks. Twelve luspatercept-treated pts did not require a transfusion after the first dose of luspatercept up to Wk 48 or until time of analysis; as of Jan 7, 2019 data cutoff, 3 (25%) of those pts maintained response. AEs occurring more frequently with luspatercept vs placebo (fatigue, diarrhea, asthenia, dizziness) occurred early (Cycles 1-4), were mainly grade 1 or 2, decreased over time, and were not associated with a higher dose level. Progression to acute myeloid leukemia was similar in pts receiving luspatercept (n = 3 [2.0%]) and those receiving placebo (n = 1 [1.3%]). Conclusions: Most LR-MDS pts achieving RBC-TI and/or HI-E with luspatercept in the MEDALIST study had multiple responses with durable clinical benefit superior to that of pts receiving placebo, including those with a high baseline transfusion burden. AEs were mainly grade 1 or 2, decreased over time, and were not correlated with a higher dose level. Disclosures Fenaux: Aprea: Research Funding; Jazz: Honoraria, Research Funding; Astex: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding. Mufti:Cellectis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Buckstein:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding. Santini:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria; Acceleron: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees. Díez-Campelo:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Finelli:Celgene Corporation: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau. Ilhan:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees. Komrokji:DSI: Consultancy; JAZZ: Consultancy; celgene: Consultancy; Agios: Consultancy; pfizer: Consultancy; Novartis: Speakers Bureau; JAZZ: Speakers Bureau; Incyte: Consultancy. List:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zeidan:Trovagene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Research Funding; Jazz: Honoraria; Ariad: Honoraria; Agios: Honoraria; Novartis: Honoraria; Astellas: Honoraria; Daiichi Sankyo: Honoraria; Cardinal Health: Honoraria; Seattle Genetics: Honoraria; BeyondSpring: Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Acceleron Pharma: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Medimmune/AstraZeneca: Research Funding; Otsuka: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Verma:Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria; BMS: Research Funding; Janssen: Research Funding. Laadem:Celgene Corporation: Employment, Equity Ownership. Ito:Celgene Corporation: Employment, Equity Ownership. Zhang:Celgene Corporation: Employment, Equity Ownership. Rampersad:Celgene Corp: Employment, Equity Ownership. Sinsimer:Celgene Corporation: Employment, Equity Ownership. Linde:Acceleron Pharma: Employment, Equity Ownership; Fibrogen, Inc.: Equity Ownership; Abbott Laboratories, Inc.: Equity Ownership. Garcia-Manero:Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Platzbecker:Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. OffLabel Disclosure: Luspatercept is an investigational therapy that is not approved for any use in any country. Luspatercept is currently being evaluated for potential use in patients with anemia due to myelodysplastic syndromes, beta-thalassemia, or myelofibrosis.

Introduction: Several studies have attempted to describe the characteristics associated with large granular lymphocytosis (LGL) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its clinical significance. However the clinical features of LGL lymphocytosis in the allo-HSCT setting is still sparse. The current study represents a detailed review of 667 patients transplanted in a single center with the objective to define the incidence of LGL lymphocytosis, to identify associations with transplant-related clinical parameters and to assess the impact on transplant related outcomes. Patients and Methods: During a 14-year follow up period (2005-2017) in this unicentric cohort study, we identified 19 patients (2.8%) with a significant LGL lymphocytosis, among 667 consecutive adult patients who underwent allo-HSCT. LGL lymphocytosis was defined as the presence of at least two of the following criteria: (1) sustained lymphocytosis above 3.0x109/L observed in at least three consecutive determinations over a time frame of 2-3 months, (2) predominance (that is, >30%) of LGLs in the peripheral blood, (3) confirmation of clonality by T-cell receptor analysis using PCR. Flow cytometry analyses were performed using the flow cytometry system FACSCalibur (BD Biosciences, San Jose, CA). The immunophenotyping of the lymphocytes included the following antibody panel: CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD30, CD56, CD57, HLA-DR, TCRab, and TCRgd. T-LGL expansion was defined as an abnormal T cell population type CD31, CD81, or CD41, with expression of at least 1 of the NK markers (CD16, CD57, or CD56), and with presence of LGLs in peripheral blood films. Results: A total of 19 (Female/ male: 10 [52.6 %]/ 9 [47.4 %]) patients included into the study met the morphological criteria for LGL lymphocytosis. The median age of the patients was 46 years (range, 18- 62 years). The majority of the patients (64.7 %) had the diagnosis of acute myeloid leukemia. The stem cell source was peripheral blood stem cells (PBSC) in 15 patients (88.2 %) and most of the patients underwent an allo-HSCT with a MAC (n= 13) regimen at a median of 25.1 months from allo-HSCT. The median onset of LGL lymphocytosis was 11.5 (2.1- 55.7) months and median lymphocyte count at the time of diagnosis of LGL lymphocytosis was 5400/ mL (5170- 8700/ mL). None of the patient showed cytopenia, palpable splenomegaly, and none of them had typical signs or symptoms of an autoimmune disease. In addition; GvHD, viral infections, disease relapse and loss of donor chimerism were excluded during lymphocytosis. Samples from 19 patients were phenotyped by flow cytometry. These studies confirmed a T cell phenotype of LGLs in the majority of patients (n=12). Two patients presented with LGLs consistent with NK cells and seven showed properties of a mixed NK/T-cell lineage. A monoclonal LGL population of T-cell origin was identified in eight (42.1%) of these patients. With a median follow-up of 12.2 months none of the patients demonstrating increased LGL values has progressed to LGL leukemia or any other lymphoproliferative disorder. Four patients experienced cutaneous acute GVHD followed by a progressive chronic GVHD. Two patient developed a grade II acute cutaneous GVHD which rapidly responded to steroids in addition to cyclosporin A. Five patients had de novo chronic GVHD. In subgroup analysis, we compared the OS of monoclonal and oligoclonal LGL lymphocytosis and 1-year-OS was longer but non-significantly in monoclonal LGL lymphocytosis group; 75% ± 1.6% vs. 44.4% ± 2.2%, respectively (p= 0.21) (Figure). Median PFS was 28.8 months in oligoclonal LGL lymphocytosis group and 8.3 months in monoclonal LGL lymphocytosis group but the number of patients in this group does not provide enough statistical power to confirm whether the differences in PFS were statistically significant (p= 0.3). At the time of this report, three patients have died. The primary cause of death was relapse of the primary disease in one of the patients, whereas 2 patients died of TRM (10.5%). Discussion: In conclusion, we observed LGL lymphocytosis in 2.8 % of a large cohort of post allo-HSCT survivors. Our data indicate that, even if monoclonal, post-transplantation LGL expansion may be considered as an expression of chronic stimulation triggered by allo-HSCT rather than the result of a malignant transformation. Disclosures Özcan: Amgen: Honoraria, Other: Travel support; BMS: Other: Travel support; Jazz: Other: Travel support; Sanofi: Other: Travel support; Bayer: Research Funding; Novartis: Research Funding; Roche: Other: Travel support, Research Funding; Archigen: Research Funding; Takeda: Honoraria, Other: Travel support, Research Funding; Abdi Ibrahim: Other: Travel support; MSD: Research Funding; AbbVie: Other: Travel support, Research Funding; Janssen: Other: Travel support, Research Funding; Celgene Corporation: Research Funding, Travel support. Ilhan:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Beksac:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Introduction:Generic imatinib formulations are increasingly being used as more affordable alternatives worldwide and a few studies have evaluated the safety and efficacy of these formulations prospectively. We have retrospectively analyzed our CML cohort in terms of first line treatment of Glivec versus generic imatinib. This study aims to evaluate the safety and efficacy of generic imatinib products in chronic phase chronic myeloid leukemia as first line treatment. Methods:We have retrospectively analyzed our CML cohort from January 2000 to December 2018 treated with either Glivec or one of generic imatinib formulations. All of our patients (with 1 exception) were initiated imatinib in chronic phase in less than 56 days from diagnosis. All of our patients were followed in accordance with European Leukemia Net (ELN) 2013 recommendations and national hematology association CML guidelines and response definitions were applied according to ELN 2013 criteria. Event free survival (EFS) was defined as the time between treatment initiation and either loss of hematological response, progression to accelerated phase (AP) or blastic phase (BP), or death from any cause. Progression free survival was defined as the time between treatment initiation and transformation to AP, BP or death while on imatinib. For statistical analyses SPSS version 21.0 was used. All p values < 0.05 were considered statistically significant. Results:A total of 192 patients were analyzed comparing 102 (53.1 %) patients on Glivec with 90 patients on (476.9 %) generic formulations. 99 (51.6 %) were female patients. The median age of our population was median 46 years (14-88 years) for Glivec and median 51 years (19-79 years) for generic group (p=0.01). Risk stratifications according to Sokal, Hasford and ELTS scores were run for both Glivec and generic formulation groups. Most of the patients had low risk according to Sokal (137, 71.4%) and Hasford (116, 60.4 %) but intermediate risk according to ELTS (113, 58.9 %) scoring systems. There was no statistically significant difference in the gender distribution, Sokal, Hasford, ELTS scores and ECOG between the two groups. The median time to initiate imatinib treatment was 23.5 (1- 156) days for Glivec group and 13 (1- 51) days generic group (p< 0.05). But the late onset of the treatment was not associated with treatment failure or death. The median follow up was 119.8 (3.7- 250.5) months for Glivec group and 43.6 (2- 150) months for generic groups, respectively (p< 0.05). This difference might be explained by the fact that Glivec has been on the market for about two decades. Similar rates of grade> 2 hematological and non- hematological toxicity were seen in Glivec (4.9 %) and generic groups (3.3 %), respectively (p> 0.05). The rates of treatment failure at 3 months were significantly higher in generic formulation (6.7 %) group than Glivec (2.9 %) group (p< 0.05). Also, the rates of treatment failure at 6 months were significantly higher in generic formulation (3.3 %) group than Glivec (0.9 %) group (p< 0.05). Optimal molecular response rate at 3 months was 76.5 % (n=78) for Glivec and 32.2 % (n=29) for generic groups (p< 0.001). Also, optimal molecular response rate at 6 months was 69.6 % (n=71) for Glivec and 45.6 % (n=41) for generic groups (p= 0.01). Median EFS was found significantly higher for Glivec group compared to generic group (168 mos (95% CI: 159-177 mos) vs 74.6 mos (95% CI: 56-93); p Conclusion: We found that complete hematological response rates at 3 and 6 months were similar in both groups, but in early phase of treatment the optimal response rates of Glivec group was statistical significantly higher than generic group. Generic group presented with a lower rate of optimal response at 3 months but 13.4 % improvement in optimal response rates was observed at six months. No significant difference in safety concerns was observed between the groups. We recommend that these results from single center should be clarified in a prospective, randomized study including larger population. Figure Disclosures Özcan: AbbVie: Other: Travel support, Research Funding; MSD: Research Funding; Novartis: Research Funding; Amgen: Honoraria, Other: Travel support; BMS: Other: Travel support; Jazz: Other: Travel support; Sanofi: Other: Travel support; Abdi Ibrahim: Other: Travel support; Janssen: Other: Travel support, Research Funding; Bayer: Research Funding; Celgene Corporation: Research Funding, Travel support; Takeda: Honoraria, Other: Travel support, Research Funding; Archigen: Research Funding; Roche: Other: Travel support, Research Funding. Beksac:Celgene: Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

To the editor: Idiopathic CD4 lymphopenia represents a heterogeneous group of combined primary immunodeficiencies with markedly reduced CD4+ T-cell counts. Although several genetic etiologies including MHC class II deficiency[1][1] or mutations in RAG1 ,[2][2] MST1 ,[3][3] or LCK [4][4] have been

Background: High burden of patients with hematological malignancies are diagnosed >65 years old. Since then, geriatric interventions can improve quality of life, compliance to therapy and overall survival. Geriatric screening is the best tool to access patients' prognosis. In this study, our aim is to identify our geriatric patients with different geriatric scoring systems to evaluate their prognostic value for overall survival (OS). Patients and Methods: We included 127 patients (age>65 years) with hematological malignancies and assessed two geriatric screening tools, G8 and Flemish version of the Triage Risk Screening Tool (fTRST) during a hospital visit at diagnosis or follow-up. G8 is considered normal if the score is >14, high risk patients in fTRST are defined as patients scored ≥ 2. OS was described using Kaplan-Meier plots, and comparisons were made using log-rank and Wilcoxon rank sum tests. Results: From 127 patients, 50 patients (39%) were newly diagnosed. The patient characteristics were defined in table. Patients under follow-up received median of 2 lines of treatment (range, 1-5); 11 patients (14%) treated with radiotherapy, 15 patients (19%) underwent autologous stem cell transplantation. Abnormal G8 score was detected in 120 patients (94%). High fTRST score was present in 72 patients (57%). Both abnormal G8 score and high fTRST score were detected more likely in follow-up patients (65% vs 40%, p=0.005).There was no statistical difference in 5-year OS in terms of abnormal G8 score or high fTRST score alone. In patients with both abnormal G8 and high fTRST scores had statistically significant lower 5-year OS compared to normal G8 and/or low fTRST scores (57% vs 85%, p=0.048) (figure). Conclusion: In investigation of two screening tools-G8 and fTRST, statistically significant survival advantage was shown if both scores were normal. Disclosures Civriz Bozdag: MSD: Research Funding; NOVARTIS: Consultancy; TAKEDA: Consultancy. Özcan:Jazz: Other: Travel support; Roche: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel payment, Research Funding; Janssen: Other: Travel Support, Research Funding; Celgene: Other: Travel support, Research Funding; Novartis: Research Funding; MSD: Research Funding; Abbvie: Other: Travel payment; BMS: Honoraria; Bayer: Research Funding; Jazz: Other; MSD: Other: travel support, Research Funding; Archigen: Research Funding. Ilhan:BMS: Speakers Bureau; Alexion: Speakers Bureau; Celgene: Speakers Bureau; Roche: Speakers Bureau.

Introduction:Donor lymphocyte infusion (DLI) is one of the therapeutic options for patients with relapsed or refractory hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). DLI can augment the graft-versus-tumor (GVT) effect; however, it can sometimes induce severe graft-versus-host disease (GVHD) and infectious complications induced by bone marrow aplasia or immunosuppressive therapy. In this study, we wanted to assess the risk factors for GVHD and transplant-related mortality (TRM) as well as disease outcomes according to the reason for DLI in patients who received DLI after allo-HSCT. Patients and Methods:We retrospectively analyzed 152 patients with various hematological malignancies who received a total of 250 DLI in our center between March 1991 and July 2018 for disease relapse and at different intervals after allo-HSCT. We used our institutional database to evaluate details and characteristics of patients and DLI outcomes. The probabilities of overall survival were calculated from the day of transplantation with Kaplan-Meier analysis using SPSS (IBM SPSS Statistics 21; IBM Corp., Chicago, IL) statistical tool kit. Results:Median patient age was 34 years (range, 14-67 years); the patient cohort included 96 males (63.2%) and 36.8 female (56%). Patients evaluated in this study were adult patients with acute myeloid leukemia (n=64), chronic myeloid leukemia (n=36), multiple myeloma (n=6), non-hodgkin lymphoma (4), primary myelofibrosis (n=6), myelodisplastic syndrome (n=3), and severe aplastic anemia (n=3). One hundred thirty-six (10.5%) and sixteen (10.5%) patients had sibling (SD) and unrelated donors (UD), respectively. The stem cell source was peripheral blood stem cells (PBSC) in 116 patients (76.3%) and the other 36 patients (23.8%) received bone marrow stem cells (BMSC). Patients underwent an allo-HSCT with a MAC (n= 109) or RIC (n=43) regimens at a median of 12.5 months from diagnosis. Cyclosporine and methotrexate were used as the main graft versus host disease (GVHD) prophylaxis in our cohort. All patients received DLI for relapse or progression. Median number of DLI was 1 (range, 1-5), the median interval between transplant and first DLI was 6 months (range, 3-86 months), median number of infused CD3+cells x 106/kg of recipient body weight was 1.5x107(range, 0.5x107- 11.1x107). The median time from relapse to the first DLI was 1.9 months (range, 0.1-32.7 months). Thirty-one patients (21%) developed acute grade II to IV GVHD and 10 patients (7%) developed extensive chronic GVHD. We could not demonstrate the higher CD3+ cell dose of DLI associated with an increased risk of GVHD. Furthermore, none of our patients presented graft hypoplasia after DLI. At a median follow-up from transplantation interval of 16.3 months (range, 0.5-188.2 months), 35 patients were still alive (%60). The OS at 1 and 3 years was 63.4±0.4 and 28.2±0.4, respectively (Figure 1). The primary cause of death was relapse of the original disease in most of the patients, whereas 14 patients died of TRM (15.3%). Discussion:Various modifications of DLI have been investigated in combination with molecular-targeted agents to enhance the antitumor effect while minimizing GVHD. Therefore, further studies of larger randomized cohorts with high quality data management are required to clarify the role of DLI in relapsed hematological malignancies. Figure. Figure. Disclosures Civriz Bozdag: TAKEDA: Consultancy; MSD: Research Funding; NOVARTIS: Consultancy. Özcan:MSD: Other: travel support, Research Funding; Jazz: Other; Janssen: Other: Travel Support, Research Funding; Novartis: Research Funding; Archigen: Research Funding; Jazz: Other: Travel support; Bayer: Research Funding; Abbvie: Other: Travel payment; Celgene: Other: Travel support, Research Funding; BMS: Honoraria; Roche: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel payment, Research Funding; MSD: Research Funding. Ilhan:Roche: Speakers Bureau; Celgene: Speakers Bureau; BMS: Speakers Bureau; Alexion: Speakers Bureau. Beksac:Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen,Janssen-Cilag,Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Introduction:High-dose Melphalan followed by autologous hematopoietic cell transplantation (ASCT) compared to conventional chemotherapies has been shown to improve survival and progression free survival (PFS) in eligible patients with multiple myeloma (MM). However cells that are resistant to the high-dose therapy and remaining in the patient and/or PBSC grafts may eventually lead to relapse. Over the past decade, data have been published on the role of circulating plasma cells (CPCs) as a poor prognostic feature at the time of diagnosis and prior to auto HSCT. But these studies have not sought this issue exclusively in PBSC grafts. The aim of this study was to analyze the impact of flow cytometric measurement of residual clonal cells within the apheresis products on outcome following ASCT. Materials and Methods:Patients with a diagnosis of MM who underwent auto HSCT at our center between January 2008- Mart 2018 were prospectively analyzed. PBSC grafts were tested for the presence of abnormal PCs (APC) and the number of normal PCs (NPC) by multi-parameter flow cytometry (FCM). Standard panel was set up with CD138FITC/CD38PE/CD45ECD/CD56PC5, CD45-CD56+PCs were identified as APC if any aberrant expression (including; CD20(loss)CD27(loss)CD28(gain)CD33(loss)CD34(gain)CD81(loss) CD117(gain)) is detected at diagnosis, the corresponding antibody was also added to the panel. Since maintenance was not an approved treatment in myeloma most patients did not receive any. Outcome was determined as response to transplant, PFS and overall survival (OS) in months by Kaplan-Meier analysis using SPSS (IBM SPSS Statistics 21; IBM Corp., Chicago, IL) statistical tool kit. Results: A total of 209 patients with MM with routine assessment for APC in the apheresis product were included in the analysis. Of these patients, 195 who underwent ASCT, met the predetermined criteria for inclusion. There were 81 (41.5%) female and 114 (58.5%) male patients. The median age at diagnosis of MM was 56 years (range, 31-71 years). The interval from the time of diagnosis to ASCT was median 7 months and median follow-up from ASCT was 49 months (range, 3-198 months). Among 195 patients, 36 (18.5%) had evidence of APC contamination in the PBSC grafts ranging between 1x10-4-12.8 x10-4of total cells. Subtypes of MM were similar among those w/wo APC. Seventy-four patients had pre and post ASCT PET-CT imaging done with 28.2% still active lesions post-ASCT. There was no correlation between PET-CR and absence of APC in grafts. Neither was there a statistically significant association between disease response Discussion:PostASCT immune response was predictive for OS only when combined with APC results. Our study provides new insight suggesting a survival advantage value of residual APC detected by FCM, even at a low sensitivity level, on OS but not PFS following ASCT. The impact of such analysis may be more relevant on PFS with better assessment of residual APC with next generation flow cytometric/sequencing approaches while taking into account maintenance. Disclosures Ilhan: Roche: Speakers Bureau; BMS: Speakers Bureau; Alexion: Speakers Bureau; Celgene: Speakers Bureau.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used to treat malignant and non-malignant hematological diseases. The impact of ABO mismatch on outcome following transplantation remains controversial. In this study, our aim is to define effects of ABO mismatch on engraftment, graft vs host disease, relapse free survival (RFS) and overall survival (OS) in patients who underwent allo-HSCT. Patients and Methods: Between 1988 and 2016, we retrospectively identified 1016 patients who underwent allo-HSCT at Ankara University School of Medicine, Department of Hematology. Chi-square and Fisher's exact tests were used where appropriate in comparison. Cox regression model and Kaplan Meier curves were applied for survival analysis. P Results: The median follow-up period was 34.7 months (range, 0.2-229). In our cohort, there were 420 (41.3%) ABO-mismatched transplants occurred including 167 (16.4%) major, 197 (19.4%) minor and 55 (5.4%) bidirectional mismatches. The pre-transplant characteristics of patients are summarized in table. Allo-HSCTs from unrelated donors and peripheral blood grafts were detected higher in ABO mismatched patients vs ABO matched patients (28% vs 11%, P Conclusion: Engraftment failure was detected higher in patients with ABO mismatch as well as major ABO mismatch was related with lower RFS and OS although the cohort is heterogeneous. Close monitoring and early treatment strategies for expectable complications would reduce the number fatal events by ABO mismatched allo-HSCT. Disclosures Civriz Bozdag: NOVARTIS: Consultancy; MSD: Research Funding; TAKEDA: Consultancy. Özcan:Abbvie: Other: Travel payment; Bayer: Research Funding; MSD: Other: travel support, Research Funding; Roche: Honoraria, Research Funding; Janssen: Other: Travel Support, Research Funding; BMS: Honoraria; Novartis: Research Funding; Jazz: Other; Jazz: Other: Travel support; Archigen: Research Funding; Celgene: Other: Travel support, Research Funding; MSD: Research Funding; Takeda: Honoraria, Other: Travel payment, Research Funding. Beksac:Deva: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ilhan:Roche: Speakers Bureau; BMS: Speakers Bureau; Celgene: Speakers Bureau; Alexion: Speakers Bureau.

Introduction:Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) still remains the only established curative approach for the treatment of acute leukemia (AL). HLA-matched sibling or relative donor (MRD) is considered the optimal donor source but when this is not available, a matched unrelated donor (MUD) is considered the best alternative. Prior studies reported comparable results of Allo-HSCT from MSD versus MUD. In this retrospective, single center review, we aimed to compare the transplantation outcomes after 10/10 or 9/10 HLA-matched related to unrelated donor transplantation in adults with AL. Patients and Methods: We retrospectively analyzed 363 consecutive patients with a diagnosis of AL who underwent their first Allo-HSCT between January 2005 and April 2018, using matched 10/10 MRD (n= 244) and MUD (n=54) or mismatched-UD (mmUD) (n=65) at Ankara University School of Medicine, Bone Marrow Transplantation Unit. Patients transplanted using cord blood or haploidentical donors were excluded to homogenously compare adult full-matched sibling or unrelated donors in the acute leukemia setting. Parameters evaluated included hematopoietic engraftment, disease relapse, transplant related complications, mortality, overall survival (OS) and disease free survival (DFS) from transplantation, and the incidence and severity of acute and chronic GVHD. Results:Baseline characteristics are summarized in Table 1. The median age was similar in all groups at the time of transplantation (p= 0.9). Median follow-up from the transplantation for all patients was 25 months (range, 1- 152.8) but median follow up was longer in the MRD group (33.6 months [range, 1-152.8]) than in the MUD and (13.3 months [range, 1-121.5]and mmUD groups (22.3 months [range, 2.3-129.4]and p=0.011). In the MRD group, 90.9% received a myeloablative conditioning (MAC) regimen, while in the MUD and mmUD groups, 73.1% and 81.3% received a MAC regimen (p=0,001). Cyclosporine and methotrexate were used as the main graft versus host disease (GVHD) prophylaxis in all groups. The proportion of patients who received in vivo T cell depletion significantly differed among the two groups (6.6% in the MRD group, 92.6% in the MUD group and 50.8% in the mmUD group, p=0.000). Peripheral blood stem cell (PBSC) was the main stem cell source in all groups (92.2% in the MRD group vs. 90.7% in the MUD group vs. 95.4% mmUD, p0.1). The median time for neutrophil and platelet engraftments was seen faster in MRD group compared to MUD and mmUD (p0.1). No statistical significance was observed for transplant related mortality (TRM) in terms of the type of donor (MUD group. mmUD groupand MRD group; 22.2%, 23.1% and 18.0%, p=0.572). Relapse incidence was similar among the groups (MRD vs. MUD vs. mmUD; 33.6% vs. 29.8% vs. 30.8%, p=0.807). Two-year leukemia free- and overall survival were not affected the donor types (Figure-1).. Conclusion:Our results suggest that, when an HLA-identical sibling donor is not available for an adult with AL who is otherwise a candidate for Allo-HSCT, a 10/10 or 9/10 UD may be used with the expectation of similar rates of TRM, LFS and OS at 2 years. Disclosures Civriz Bozdag: NOVARTIS: Consultancy; MSD: Research Funding; TAKEDA: Consultancy. Özcan:Jazz: Other: Travel support; BMS: Honoraria; MSD: Research Funding; Celgene: Other: Travel support, Research Funding; Abbvie: Other: Travel payment; Roche: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel payment, Research Funding; Novartis: Research Funding; Janssen: Other: Travel Support, Research Funding; Bayer: Research Funding; Archigen: Research Funding; MSD: Other: travel support, Research Funding; Jazz: Other. Ilhan:BMS: Speakers Bureau; Roche: Speakers Bureau; Celgene: Speakers Bureau; Alexion: Speakers Bureau. Beksac:Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen,Janssen-Cilag,Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Introduction: Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma with distinguishes clinical, biologic, and molecular characteristics. The MCL-International Prognostic Index (MIPI) incorporates age, EGOC performance status, normalized LDH level and WBC and has improved discriminatory power. The aim of this retrospective single-center study was to evaluate the clinical characteristics and response to treatment of patients with mantle cell lymphoma. Methods: This single center retrospective study included 297 adult patients diagnosed with MCL between December 2005 and May 2018. The diagnosis of MCL was rendered in accordance with the later World Health Organization (WHO) classification. Outcome was determined as response to treatment, progression free survival (PFS) and overall survival (OS) by Kaplan-Meier analysis using SPSS (IBM SPSS Statistics 21; IBM Corp., Chicago, IL) statistical tool kit. We also compared the PFS and OS according to simplified MIPI (s-MIPI) index. Results: All clinical data were available in 149 cases and these patients were further evaluated. There were 38 (26%) female and 208 (74%) male patients. The median age at diagnosis of MCL was 66 years (range, 31-93 years). The median time of follow-up was 14.5 months (range, 3-139.3 months). The median s-MIPI was 6 points (range 2-11). Most patients were in the high-risk group (62.2%). Induction chemotherapy was administered in 128/146 patients and remaining two patients had deceased after diagnosis of MCL. Altogether 115 out of 146 patients (78.8%) were treated with a combination of chemotherapy and anti-CD20 monoclonal antibody rituximab.One elderly patient received Rituximab immunotherapy only. The majority (56.5%) of the patients received CHOP with rituximab as induction chemotherapy. Thirty-one patients underwent ASCT after remission was obtained in relapse setting. Sixty-four patients (43.8%) had bone marrow involvement and 23 patients (15.7%) had extra-nodal involvement. In total 40 patients (41.2%) achieved a complete remission (CR) with an overall response rate of 63.9% after the induction therapy. During follow up, 20 relapses and 28 deaths were noted. Infection was the most common cause of death (50%). Following ASCT, OS was significantly improved; estimated median OS in transplant cohort was 115.7 months vs. 60 months compare with non-transplant group (p=0.013) (Figure-2). According to the long-rank test, estimated 5-year OS was not significantly different between intermediate-risk and high-risk s-MIPI categories (72.4%±1.2% vs. 72.6%±0.7%; p=0,202). Estimated 5-year PFS was significantly different between intermediate-risk and high-risk s-MIPI cohorts (47.1%±1.3% vs. 33%±10.3%; p=0,05). Among the transplanted patients, there is no differences between the OS of s-MIPI groups (p=0.952). No patient died or progressed in the low-risk group. Conclusion: We have confirmed the validity of the MIPI and simplifed MIPI for the prognosis of patients with MCL even in the era of rituximab. e general results of both indexes are fully comparable, facilitating the broad application of s-MIPI as a simple bedside prognostic tool. Disclosures Civriz Bozdag: MSD: Research Funding; TAKEDA: Consultancy; NOVARTIS: Consultancy. Özcan:Janssen: Other: Travel Support, Research Funding; Abbvie: Other: Travel payment; Novartis: Research Funding; Takeda: Honoraria, Other: Travel payment, Research Funding; Bayer: Research Funding; BMS: Honoraria; Celgene: Other: Travel support, Research Funding; Roche: Honoraria, Research Funding; Archigen: Research Funding; MSD: Other: travel support, Research Funding; MSD: Research Funding; Jazz: Other: Travel support; Jazz: Other. Beksac:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Deva: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ilhan:Roche: Speakers Bureau; BMS: Speakers Bureau; Celgene: Speakers Bureau; Alexion: Speakers Bureau.

Chronic graft-versus-host disease (cGVHD) is the leading cause of late treatment-related deaths among recipients of allogeneic bone marrow and blood transplants. However, cGVHD is also associated with fewer relapses. We sought to determine whether severity of cGVHD predicts the magnitude of these effects. One impediment to such an analysis is the current limited/extensive grading system for cGVHD because this classification was designed to identify patients likely to benefit from systemic immune suppression and does not capture the severity of multiorgan involvement. We, therefore, first developed a grading system predictive for survival by using data from 1827 HLA-matched sibling allotransplant recipients reported to the International Bone Marrow Transplant Registry (IBMTR). We found Karnofsky performance score, diarrhea, weight loss, and cutaneous and oral involvement to be independent prognostic variables, from which we generated a grading scheme. We tested this scheme, the limited/extensive classification system, and a classification based on clinical impression of overall cGVHD severity (mild/moderate/severe) in parallel analyses of 1092 HLA-matched sibling transplant recipients from the IBMTR and 553 recipients of unrelated donor marrow from the National Marrow Donor Program. Presence of cGVHD was associated with fewer relapses (relative risk [RR], 0.5-0.6) but more treatment-related mortality (RR, 1.8-2.8) in the 3 analyses. No grading scheme correlated cGVHD severity with relapse rates, but all schemes predicted treatment-related mortality. Survival and disease-free survival of the most favorable cGVHD group in each scheme were similar, or better, than those of patients without cGVHD; these patients may not need aggressive or extended immune suppression.