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Background The relative benefits of haploidentical HCT using PTCy compared to traditional matched-sibling donor, traditional unrelated donor and umbilical cord blood (UCB) allogeneic HCT for adult acute lymphoblastic leukemia (ALL) is still being defined. Methods We performed a retrospective analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database comparing post-HCT outcomes of haploidentical donors with PTCy to HLA-identical sibling donors, 8/8 HLA-MUDs, 7/8 HLA-MUDs, and UCB. Outcomes were overall survival (OS) leukemia-free survival (LFS), relapse, non-relapse mortality (NRM), grade 2-4 and grade 3-4 acute graft-versus-host disease (aGVHD), and chronic GVHD (cGVHD). Eligible patients were adults with ALL in complete remission (CR1, CR2, or CR3) undergoing first allogeneic HCT from 2013 to 2017. Key exclusion included not receiving PTCy for haploidentical HCT and ex vivo T-cell depleted or CD34-selected grafts. Cox proportional hazards multivariable regression analysis was used to compare the treatment groups. Results 4201 patients were studied: 393 haploidentical donor (92 centers), 1627 HLA-identical sibling donor (206 centers), 1646 8/8 HLA-MUD (181 centers), 230 7/8 HLA-MUD (90 centers), and 305 UCB (79 centers). Groups were well matched, however, notable differences between included race, time from diagnosis to HCT (CR1 only), conditioning regimen intensity, donor age, graft source for non-cord (peripheral blood or bone marrow), GVHD prophylaxis modality, and the use of in vivo T-cell depletion. Compared to other groups, haploidentical HCT had the lowest percentage of non-Hispanic white patients (43% vs. 49-74%), was more likely to use reduced-intensity conditioning (42% vs 17-25%), and was more likely to use bone marrow (41% vs. 14-29%). In multivariate analysis comparing haploidentical to matched-sibling donor HCT, no differences were observed in OS, LFS, NRM, relapse, or aGVHD. Compared to haploidentical HCT, the risk of cGVHD was significantly higher with matched-sibling donor HCT (D/R sex match F/M, HR 2.59, P<0.001, D/R sex match, other, HR 1.37, P=0.003). Comparing haploidentical to 8/8 HLA-MUD HCT, no differences were seen in OS, LFS, relapse, or Grade 2-4 aGVHD but 8/8 HLA-MUD HCT was associated with increased incidences of NRM (HR 1.42, P=0.02), grade 3-4 aGVHD (HR 1.59, P=0.005), and cGVHD (HR D/R sex match F/M, HR 2.91, P<0.001, D/R sex match, other, HR 1.38, P=0.001). Comparing haploidentical to 7/8 HLA-MUD HCT, no differences were seen in LFS or relapse but 7/8 HLA-MUD HCT was associated with worse OS (HR 1.38, P=0.01) and increased incidences of NRM (HR 2.13, P=<0.001), grade 2-4 aGVHD (HR 1.33, P=0.04) , grade 3-4 aGVHD (HR 1.86, P=0.003), and cGVHD (HR 1.72, P=<0.001). Comparing haploidentical to UCB HCT, no differences were seen in late OS (>18 months), late LFS, relapse, or cGVHD. Compared to haploidentical HCT, UCB HCT was associated with worse early OS (≤18 months, HR 1.93, P<0.001), worse early LFS (HR 1.40, P=0.007) and increased incidences of NRM (HR 2.08, P<0.001), grade 2-4 aGVHD (HR 1.83, P<0.001), and grade 3-4 aGVHD (HR 1.97, P<0.001). Similar outcomes were observed in sensitivity analyses restricting cohorts to (1) MA conditioning with peripheral blood stem cells and (2) calcineurin inhibitor-based GVHD prophylaxis for matched-sibling, unrelated donor, and UCB HCT. Conclusions For OS and LFS, haploidentical HCT using PTCy for adult ALL was superior to traditional HCT using 7/8 HLA-MUDs and UCB but equivalent to traditional HCT using matched-sibling donors and 8/8 HLA-MUDs. Results were consistent across all subgroups. Haploidentical HCT had a lower incidence of aGVHD compared to 8/8 HLA-MUD, 7/8 HLA-MUD, and UCB HCT and a lower incidence of cGVHD compared to matched-sibling donor, 8/8 HLA-MUD, and 7/8 HLA-MUD HCT. Based on these data, haploidentical HCT with PTCy results in similar survival with less GVHD compared to traditional matched-sibling and 8/8 HLA-matched donor HCT and is the superior alternative donor option for adult patients with ALL needing allogeneic HCT in CR. Figure Disclosures Wieduwilt: Leadiant: Research Funding; Shire: Research Funding; Merck: Research Funding; Macrogeneics: Research Funding; Amgen: Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. de Lima:Incyte: Other: Personal Fees, advisory board; BMS: Other: Personal Fees, advisory board; Pfizer: Other: Personal fees, advisory board, Research Funding; Celgene: Research Funding; Kadmon: Other: Personal Fees, Advisory board. Kebriaei:Novartis: Other: Served on advisory board; Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Amgen: Other: Research Support; Jazz: Consultancy. Hourigan:Merck: Other: Research Support (CRADA); Sellas: Other: Research Support (CRADA). Weisdorf:FATE Therapeutics: Consultancy; Incyte: Research Funding.

Background: Allogeneic HCT continues to be the optimal consolidation strategy for many patients with AML. Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes. We tested the prognostic ability of a modified (mELN) classification system based on available CIBMTR genetic data, to predict post-transplant outcomes. Methods: Adult patients with a diagnosis of AML in first complete remission (CR1) with available pre-transplant cytogenetic and molecular mutational data, receiving a first allogeneic HCT from 2013-2017, were included. Patients were stratified according to mELN genetic classification in three distinct groups: favorable (Fav), intermediate (IM) and adverse (Adv). Clinical outcomes following HCT were compared among groups after adjusting for significant patient, disease, and transplant-related variables. The primary endpoint was disease free survival (DFS). Secondary endpoints were overall survival (OS), non-relapse mortality (NRM), cumulative incidence of relapse, acute GVHD, and chronic GVHD. Cox proportional hazard models were used to compare endpoints among mELN risk groups, age groups and genetic subsets within the adverse-risk group. Results: Demographic characteristics are summarized in Table 1. 2289 patients (Fav, n=181; IM n=1185; and Adv n=923) met the inclusion criteria. Median follow-up for survivors was 35 months. Importantly, 41% of transplant recipients (n=936) were >60 years, 76% (n=1743) had de novo AML and 48% (n=1111) received a myeloablative conditioning regimen. Univariate analysis (UVA) demonstrated significant differences in 2-year OS (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p<0.001); DFS (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p<0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p<0.001) There were no significant differences in NRM (p=0.467) or the incidence of acute (p=0.423) and chronic GVHD (p=0.442) among mELN groups. Initial multivariate analysis (MVA) of mELN risk groups indicated that there was no significant difference in clinical outcomes between the Fav and IM risk groups. Thus, these groups were combined for subsequent analyses. Adv risk (vs. Fav/IM) led to significantly worse OS (HR 1.39 [1.24-1.57] p=<0.001), DFS (HR 1.32 [1.18-1.48] p=<0.001), and relapse (HR 1.42 [1.23-1.63] p=<0.001) (Table 2). This mELN classification effectively stratified both younger (<60 y/o) and older (>60 y/o) patients for OS (Adv vs. Fav/IM HR for <60: 1.43 [1.21-1.69] p<0.001; >60: 1.44 [1.21-1.72] p<0.001), DFS (Adv HR for <60: 1.31 [1.12-1.53] p<0.001; >60: 1.41 [1.19-1.66] p<0.001) and relapse (Adv HR for <60: 1.44 [1.20-1.74] p<0.001, >60: 1.42 [1.15-1.76] p=0.001). NRM was higher for older patients (>60 y/o) in both the Fav/IM (HR 1.40 [1.10-1.78] p=0.007) and Adv-risk cohorts (HR 1.59 [1.18-2.13] p=0.002). Genetic subset comparisons within the adverse-risk group showed that patients carrying monosomy 5, del(5q) or monosomy 7 had inferior 2-year OS (42.6%, p<0.001) and DFS (35.2%, p<0.001), as well as higher rates of relapse (45%, p= 0.002) when compared to other patients within the Adv-risk cohort (OS 60%, DFS 50.8%, relapse 33.5%). Conclusion: Stratification using mELN criteria resulted in clear prognostic separation of OS, DFS and relapse in this large cohort of AML patients undergoing allogeneic HCT. While Fav and IM groups had similar OS, DFS and relapse rates; patients in the Adv risk group had the highest risk of relapse and inferior DFS/OS. However, the majority of patients in all cohorts had favorable outcomes for HCT in CR1. Our findings confirm the value of a combined genetic prognostic model in the AML HCT setting and justify the use of this stratification system in future HCT trials. Correlation of genetic subtypes with other important transplant variables, such as conditioning intensity and pre-transplant MRD status deserves further evaluation. There remains a subset of Adv-risk patients for which post-transplant outcomes continue to be poor, even when transplanted in CR1. Novel peri-transplant pre-emptive/therapeutic strategies are urgently needed for this high-risk cohort. Disclosures de Lima: Celgene: Research Funding; Pfizer: Other: Personal fees, advisory board, Research Funding; BMS: Other: Personal Fees, advisory board; Incyte: Other: Personal Fees, advisory board; Kadmon: Other: Personal Fees, Advisory board. Komanduri:Kiadis: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Atara: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kebriaei:Ziopharm: Other: Research Support; Jazz: Consultancy; Kite: Other: Served on advisory board; Amgen: Other: Research Support; Novartis: Other: Served on advisory board; Pfizer: Other: Served on advisory board. Bhatt:National Marrow Donor Program: Research Funding; Rigel Pharmaceuticals: Other; Jazz: Research Funding; Agios: Other: Personal Fees; Incyte: Other: Personal Fees, Research Funding; Takeda: Other: Personal Fees; Partner Therapeutics: Other: Personal Fees; Pfizer: Other, Research Funding; CSL Behring: Other; Tolero Pharmaceuticals: Research Funding; Oncoceutics: Other: Drug support for a trial; Partnership for health analytic research, LLC: Other: Personal Fees; Omeros: Other: Personal Fees; Abbvie: Other: Personal Fees, Research Funding. Saad:Orcabio: Other: research support; Kadmon: Other: research support; Amgen: Other: research support; Incyte Pharmaceuticals: Other: Personal Fees; Magenta Therapeutics: Other: Personal Fees. Copelan:Amgen: Membership on an entity's Board of Directors or advisory committees. Defilipp:Incyte: Research Funding; Regimmune: Research Funding; Syndax Pharmaceuticals: Consultancy. Nishihori:Karyopharm: Other: Research support to institution; Novartis: Other: Research support to institution. Weisdorf:Incyte: Research Funding; FATE Therapeutics: Consultancy.

Abstract Background: HLA associations for the risk of developing MM have been described in various non-Caucasian ethnic groups but have not revealed consistent results. Racial and genetic differences in cytokine polymorphisms linked to extended haplotypes; association of autoimmune disorders with HLA types; the proximity of the HLA Class I and II genes to TNF and other Class III genes responsible for complement and cytokines suggest that HLA polymorphisms may be associated with the risk of developing MM. Aim: We compared HLA-A,-B and -DRB1 2-digit allele and haplotype frequencies in patients with MM to the normal population in order to define HLA specificities associated with the risk of developing MM. Methods: A cohort of 1803 US Caucasian patients with MM were identified based on availability of HLA-A, B, DRB1 DNA-based typing or serologic typing converted to 2-digit alleles. These patients had either received a matched sibling allogeneic transplant for MM reported to the CIBMTR (N=174) or had HLA typing performed for an unrelated donor search conducted through the US National Marrow Donor Program (NMDP) (N=1629). HLA-A, B and DRB1 allele frequencies among patients were compared to A-B-DRB1 frequencies in HLA typed healthy US Caucasian controls (N= 433838) from the NMDP database. The most frequent alleles among patients and controls as well as HLA haplotype frequencies generated using the EM (expectation-maximization) algorithm were compared using Chi-Square analysis with Bonferroni correction for the number of comparisons. Results: Patients with MM had a median age of 49 (range 3–78) years and M/F ratio of 1.86 (1172/631). The controls had a median age of 44 (range 18–60) years and M/F ratio of 0.735 (183785/250053). Comparison of HLA-A, -B and –DRB1 single-locus allele frequencies between the myeloma patients and controls (those in the top 10 in either group) revealed similarity except for HLA-B*07 and B*44. B*44 was observed less frequently among the patients (a protective effect) frequency (f): 0.126 vs 0.145 (p= 0.005, Odds Ratio (OR): 0.848). On the contrary, HLA-B*07 was more common (a predisposing effect) among patients (OR: 1.135, p=0.047). Among the top 20 two locus (HLA-A-B and HLA-B-DRB1) haplotype frequencies in either group, B*44-DRB1*13 and B*07-DRB1*13 were significant: OR: 0.506 and 1.714 (p=0.003 and 0.007) respectively. A-B-DRB1 haplotype comparisons showed significance for: A*02-B*44-DRB1*04 (OR: 0.686, p=0.021), A*02-B*44-DRB1*13 (OR: 0.445, p=0.065) and A*02-B*07-DRB1*04 (OR: 1.968, p=0.029) confirming the single and B-DRB1 combination comparison results. Significantly different HLA-A, -B and -DRB1 single-locus allele or haplotype frequencies between patients and controls are shown in table 1. Conclusion: This is the largest epidemiologic study of HLA allele frequencies and the first study on HLA haplotype frequencies in MM. We observed a protective effect on the risk of developing MM with B*44 and a predisposing effect with B*07. Similar predisposing and protective haplotype associations were observed with A*02-B*07-DRB1*04 and A*02-B*44-DRB1*04 respectively. A revised analysis using a gender-matched control group is in progress. Further study including major histocompatibility region SNP mapping and candidate gene testing will help elucidate the genetic basis underlying this observation. Table 1. Allele/Haplotype Frequency Controls Frequency MM Odds Ratio (OR) P value (corrected) OR = odds of observing the allele/haplotype in patients compared to controls A*02-B*44-DRB1*13 0.00620 0.00277 0.445 0.065 B*44-DRB1*13 0.01359 0.00686 0.507 0.003 A*02-B*44-DRB1*04 0.02605 0.01813 0.686 0.021 B*44 0.14552 0.12618 0.848 0.005 B*07 0.13313 0.14836 1.134 0.047 B*07-DRB1*13 0.00814 0.01397 1.714 0.007 A*02-B*07-DRB1*04 0.00367 0.00721 1.968 0.029

Optimal post-remission therapy for adolescents and young adults (AYAs, 16-39 years) with Ph-negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1) is not well established. We hypothesized that post-remission therapy with a pediatric-inspired regimen would yield superior outcomes to myeloablative allogeneic HCT for AYA patients with Ph- ALL in CR1. We compared overall survival (OS), disease-free survival (DFS), relapse, and non-relapse mortality (NRM) for patients receiving post-remission therapy on CALGB 10403 to a contemporary matched AYA cohort undergoing myeloablative allogeneic HCT in CR1 reported to the CIBMTR (Table). The allogeneic HCT cohort consisted of patients 16-39 years of age with Ph- ALL in CR1 undergoing myeloablative transplant from a matched sibling/relative or unrelated donor using peripheral blood or bone marrow stem cells between 11/2002 and 8/2012 in the United States. Patients receiving post-remission therapy with pediatric-inspired chemotherapy had superior OS (P<0.0001), DFS (P=0.0011), and NRM (P<0.001) compared to allogeneic HCT. Patterns of relapse were time-dependent and examined in the Cox model. In multivariate analysis of Cox model, receiving allogeneic HCT was associated with inferior OS (HR 1.99, 95% CI 1.5-2.65, P <0.001), inferior DFS (HR 1.51, 95% CI 1.17-1.94, P 0.002), and increased NRM (HR 3.93, 95% CI 2.53-6.10, P <0.001; Figure). In the early post-remission period (≤15 months after CR1), relapse was more likely with allogeneic HCT (HR 1.63, 95% CI 1.03-2.59, p=0.04) whereas beyond 15 months after CR1 relapse was more likely in the chemotherapy arm (HR 0.35, 95% CI 0.19-0.62, P <0.001; Figure). Obesity (BMI ≥30) was independently associated with inferior OS (HR 2.22, 95% CI 1.69-2.91, P<0.001), inferior DFS (HR 1.96, 95% CI 1.52-2.53, P <0.001), increased relapse (1.90, 95% CI 1.37-2.64, P <0.001), and increased NRM (HR 1.99, 95% CI 1.33-2.97, P <0.001). Extramedullary disease at diagnosis was independently associated with inferior OS (HR 1.34, 95% CI 1.00-1.79, P=0.05). We conclude from this large retrospective study that post-remission therapy with pediatric-inspired chemotherapy as given on CALGB 10403 was superior to allogeneic HCT in CR1 for OS, DFS, and NRM in AYAs with newly-diagnosed Ph-negative B- and T-cell ALL. Late relapse was more likely with chemotherapy whereas early relapse was more likely with allogeneic HCT. Future study should aim to elucidate the impact of measurable residual disease at CR1 and high-risk genetics, including Ph-like ALL, on the superiority of post-remission pediatric-inspired chemotherapy over allogeneic HCT. Figure. Allogeneic HCT (HCT) vs. CALGB 10403 pediatric-inspired chemotherapy (chemo) after CR1: Adjusted (left-truncated) overall survival, disease-free survival, cumulative incidence of relapse, and cumulative incidence of non-relapse mortality. Disclosures Wieduwilt: Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen, Leadiant, Merck, Servier: Research Funding; Reata Pharmaceuticals: Equity Ownership. Stock:Astellas: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria; Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; UpToDate: Honoraria. Advani:Macrogenics: Research Funding; Abbvie: Research Funding; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Kite Pharmaceuticals: Consultancy; Glycomimetics: Consultancy, Research Funding. Luger:Ariad: Research Funding; Biosight: Research Funding; Celgene: Research Funding; Cyslacel: Research Funding; Daichi Sankyo: Honoraria; Genetech: Research Funding; Jazz: Honoraria; Kura: Research Funding; Onconova: Research Funding; Pfizer: Honoraria; Seattle Genetics: Research Funding; Agios: Honoraria. Larson:Novartis: Honoraria, Other: Contracts for clinical trials; Agios: Consultancy; Celgene: Consultancy. Tallman:Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioLineRx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biosight: Research Funding; Nohla: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orsenix: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Research Funding; KAHR: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellerant: Research Funding; Tetraphase: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Delta Fly Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; UpToDate: Patents & Royalties; Oncolyze: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kebriaei:Kite: Honoraria; Jazz: Consultancy; Amgen: Research Funding; Pfizer: Honoraria. Weisdorf:Pharmacyclics: Consultancy; Incyte: Research Funding; Fate Therapeutics: Consultancy.

PURPOSETo compare the outcomes of patients with Hodgkin or non-Hodgkin lymphoma undergoing nonmyeloablative haploidentical or unrelated cord blood (UCB) hematopoietic cell transplantation.PATIENTS AND METHODSWe retrospectively studied 740 patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received transplantations from 2009 to 2016. Data were reported to the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation, Eurocord, or Center for International Blood and Marrow Transplant Research. Of the 526 patients who received haploidentical transplantation, 68% received bone marrow and 32% received peripheral blood. All patients received a uniform transplantation conditioning regimen (2 Gy of total-body irradiation, cyclophosphamide, and fludarabine) and graft-versus-host disease prophylaxis (calcineurin inhibitor and mycophenolate). In addition, patients who received a haploidentical transplantation received posttransplantation cyclophosphamide.RESULTSCompared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55; P = .001; and HR, 1.59; P = .005, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; P = .002; and HR, 1.86; P < .0001), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91; P = .0001; and HR, 2.27; P = .0002, respectively).CONCLUSIONWhen considering HLA-mismatched transplantation for Hodgkin or non-Hodgkin lymphoma, the data support haploidentical related donor transplantation over UCB transplantation.

Patients who develop therapy-related myelodysplastic syndromes (t-MDSs) or acute myeloid leukemia (t-AML) following prior chemotherapy or an autologous hematopoietic cell transplant (HCT), have a poor prognosis. An earlier analysis of allogeneic HCT (n=868, 1990-2004) showed 5-year overall survival (OS) and disease free survival (DFS) were 22% and 21% (reference). Furthermore, older age, graft source other than a HLA-matched sibling or HLA well matched unrelated donor (URD), t-AML not in remission or advanced t-MDS, and poor risk cytogenetics were associated with worse outcomes. Modern supportive care and conditioning regimens including reduced intensity (RIC) regimens may have improved outcomes. Therefore we analyzed 1531 HCT for t-AML (n = 772) or t-MDS (n = 759) performed from 2000 to 2014. The median age at transplant was 52 (18-77) for t-AML and 59 (18-74) for t-MDS. Eleven percent of patient with t-AML and 24% of patient with t-MDS had a prior autologous transplant. A myeloablative regimen was used for conditioning in 61% of patients with t-AML and 49% of patients with t-MDS (Table 1). For t-AML, the 5-year non-relapse mortality (NRM) and relapse rates (RR) were 33% (95% confidence interval [CI], 30-36) and 43% (40-47), respectively. For t-MDS, the 5 year TRM and RR were 32% (29-36) and 46% (43-50), respectively. Five year DFS and OS were 24% (21-27) and 25% (22-28), respectively, for patients with t-AML. Five year DFS and OS were 21% (18-24) and 27% (23-31), respectively, for patients with t-MDS. In multivariate analysis, t-AML OS and DFS was worse for: previous autologous transplant, relapsed disease at HCT, intermediate or adverse cytogenetics, partially matched and cord blood grafts, and RIC. For t-MDS: age greater than 60, previous autologous transplant, very high IPSS score, and use of HLA-partially matched unrelated grafts. A significant minority of patients with t-AML and t-MDS can achieve long-term remission with allogeneic HCT, yet risks of both NRM and relapse are still excessive. Relapse is the major cause of treatment failure. Disclosures Metheny: Takeda: Speakers Bureau; Incyte: Speakers Bureau. Weisdorf:Incyte: Research Funding; Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy. Kebriaei:Jazz: Consultancy; Amgen: Research Funding; Pfizer: Honoraria; Kite: Honoraria.

Although some data (Scott, JCO 2017) suggest that myeloablative conditioning (MAC) is preferred for allogeneic hematopoietic cell transplantation (HCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), these data were not informed by analysis of disease specific risk factors. We analyzed AML and MDS HCT outcomes stratified by the disease risk index (DRI) in order to identify the preferred transplant conditioning intensity (reduced-intensity conditioning [RIC] vs. MAC). In this large CIBMTR registry study we identified 4387 adult patients (age 40-65 years) who received HCT for AML (68%) or MDS (32%) between 2009 and 2015. DRI was stratified as low/ intermediate risk (1539 MAC and 999 RIC) and high/ very high risk (1121 MAC and 728 RIC). Examining the low/ intermediate risk DRI cohort (Table), RIC was associated with lower risk of TRM (HR=0.74, 95% CI 0.62-0.88; p<0.001) but significantly higher risk of relapse (HR=1.54, 95% CI 1.35-1.76; p<0.001). As a result, RFS in this cohort was significantly worse with RIC (HR=1.19, 95% CI 1.07-1.33; p=0.001). In the high/ very high risk DRI cohort, RIC resulted in similar TRM (HR=0.83, 95% CI 0.68-1.00; p=0.051) but again significantly higher risk of relapse (HR=1.23, 95% CI 1.08-1.41; p=0.002). RFS in high/ very high risk DRI cohort was similar between RIC and MAC. Adjusted outcome curves for the 3 endpoints are shown in the Figure. In this large study of HCT for AML or MDS stratified by DRI, RIC was independent predictor of lower TRM, but significantly higher risk of relapse. The MAC was an independent predictor of lower relapse in both low/ intermediate and high/very high DRI groups. However, MAC only resulted in RFS benefit in the low/ intermediate group where the magnitude of impact on relapse was not offset by the higher TRM. In adults with AML or MDS aged 40-65 years, these data support MAC as the preferred conditioning intensity for low/ intermediate risk DRI, whereas MAC does not provide significant benefit in those with high/ very high risk DRI. Safer, yet still potent MAC regimens could benefit this higher risk group. Disclosures Bejanyan: Kiadis Pharma: Other: advisory board. Brunstein:Gamida: Research Funding; Astex: Research Funding; Magenta: Research Funding. Kebriaei:Amgen: Research Funding; Jazz: Consultancy; Pfizer: Honoraria; Kite: Honoraria; Pfizer: Honoraria; Kite: Honoraria. Weisdorf:Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy; Incyte: Research Funding.

Introduction: AML patients with intermediate or high-risk features often undergo allogeneic hematopoietic cell transplantation (alloHCT) during first complete remission (CR). The 2017 European LeukemiaNet guidelines for AML specify categories of CR: both with and without count recovery (CR vs. CRi) and with and without measurable residual disease (MRD). Previous smaller retrospective studies have suggested poorer survival outcomes after alloHCT for patients with responses less than CR. Methods: Eligible cases were determined using the CIBMTR registry. Each had AML in CR1, was ≥ 18 years, and underwent alloHCT between January 1, 2007 and December 31, 2015. MRD was defined based on the answers to qualitative questions on standard clinical reporting forms that ask if the patient is in either molecular or cytogenetic remission and if disease is detected in marrow by flow cytometry at time of HCT. The primary outcome was overall survival (OS), and secondary outcomes were non-relapse mortality (NRM), relapse and disease-free survival (DFS). The Kaplan-Meier method was used to estimate survival and cumulative incidence function was used to estimate relapse and NRM. Multivariable analysis (MVA) was performed using the Cox proportional hazards model to adjust for patient-, disease-, and transplant-related factors. Adjusted probabilities of DFS and OS, adjusted cumulative incidence curves of NRM and relapse were generated from final Cox regression models stratified on CR vs. CRi and weighted averages of covariate values using pooled sample proportion as weight function. Results: We identified 2492 cases (CR, n=1799; CRi, n=693). The main effect variable (CR vs. CRi) was missing in 262 additional patients; these patients were excluded when univariate analysis confirmed no significant associations, suggesting a random distribution of missing data. Patient characteristics are summarized in Table 1. Compared with patients with CR, patients with CRi were more likely to have a Karnofsky score <90 (38% vs. 31%) and an HCT-CI score 3+ (47% vs. 40%). Other variables were well matched between the groups. MVA demonstrated significantly increased likelihood of mortality in patients with CRi compared to those with CR with hazard ratio (HR) 1.27; 95% confidence interval (CI) (1.13-1.43) (Figure 1A). Other covariates significantly associated with shorter OS included older age, poor-risk cytogenetics, lower Karnofsky score, higher HCT-CI score, and higher white blood cell count at diagnosis. The adjusted OS probabilities at 5 year post-HCT accounted for factors from MVA model are 50% (95%CI 47-52) for patients with CR and 43% (95%CI 39-47) for patients with CRi. CRi was also associated with significantly increased NRM [HR 1.33, 95%CI(1.11-1.59)] with only a trend in increased relapse [HR 1.15, 95% CI(0.99-1.34), p=0.07] resulting in inferior DFS [HR 1.20, 95%CI(1.07-1.35)]. MRD status was available in a subset of 2297 patients, and pairwise comparison demonstrated that presence of MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD (Figure 1B). Pairwise interaction between the main effects (CR vs. CRi) and MRD status were tested with no significant findings at a level of 0.01, demonstrating that the effects of incomplete count recovery and MRD are independent of each other. Conclusions: Analysis of this large CIBMTR cohort demonstrates that survival outcomes differ among AML patients nominally in CR at the time of alloHCT. Patients with CRi and/or MRD have significantly shorter OS after alloHCT compared to those in CR, as well as shorter DFS and higher NRM. Further studies should focus on limiting NRM and reducing relapse to optimize post-alloHCT outcomes for patients with responses less than CR. Disclosures Percival: Pfizer Inc.: Research Funding; Nohla Therapeutics: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees. Kebriaei:Jazz: Consultancy; Pfizer: Honoraria; Amgen: Research Funding; Kite: Honoraria. Weisdorf:Fate Therapeutics: Consultancy; Incyte: Research Funding; Pharmacyclics: Consultancy.

Abstract Introduction: The preferred post-remission therapy for older patients (pts) with AML remains uncertain. We compared outcomes for older AML pts in CR1 receiving HCT reported to the CIBMTR to older AML pts achieving CR1 on National Clinical Trials Network induction and non-HCT consolidation therapy (CT) trials. Methods: This study focused on pts 60-75 years of age treated between 2004 to 2013. CT pts (n=211) underwent induction and consolidation on Alliance for Clinical Trials in Oncology, ECOG-ACRIN or SWOG clinical trials for initial therapy for newly diagnosed AML; the CIBMTR provided data for HCT pts (n=431). CT patients received at least one cycle of CT on study and were excluded if HCT occurred at any time. Time to event started at CR1 and pts entered at CT or HCT, respectively, using left-truncation to account for differential entry times. Results: For the CT cohort, first consolidation included standard therapy (e.g., cytarabine or a hypomethylating agent) and additional study drug (e.g., bortezomib, dasatinib, sorafenib, and Zosuquidar, gemtuzumab) or tipifarnib alone. Among HCT pts, the donor was a HLA-matched sibling or unrelated donor (URD) in 66% and the others were partially HLA-matched/mismatched URD (10%) or cord blood (24%). HCT pts were younger and more frequently had high-risk AML (high WBC, secondary AML and unfavorable cytogenetics) (Table). The median time from CR1 to HCT and CT was 3.2 and 0.5 months, respectively. Allogeneic HCT showed worse overall survival (OS) (HR=1.52, p=0.02) prior to 9 months and better OS thereafter (HR= 0.53, p <0.0001) relative to CT (figure 1A). Treatment-related mortality (TRM) was worse after HCT in the first 9 months (HR=2.8, CI: 1.5 -5.2, p=.0009), while relapse was less frequent beyond 9 months after treatment (HR = 0.42, CI: 0.29 to 0.61, p<.0001). Despite higher early TRM, HCT recipients went on to manifest superior OS [5 year OS: HCT 29% (24-34%), CT 13.8% (9 -22%)] (Figure 1A). The benefit of HCT for survival after 9 months was more prominent in those with unfavorable cytogenetics (Figure 1B). Multivariate analysis for OS showed no statistically significant effect of age or performance status, while unfavorable cytogenetics were detrimental (HR=1.74, p<.0001). Conclusions. Allogeneic HCT led to heightened early risks from TRM, but resulted in superior long-term survival in older AML pts receiving HCT relative to CT by reducing relapse. Efforts to attenuate early TRM after allogeneic HCT may further improve HCT outcomes for older pts. Disclosures Ustun: novartis: Speakers Bureau. Attar:Agios: Employment, Equity Ownership. Larson:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BristolMyers Squibb: Consultancy, Research Funding; Ariad/Takeda: Consultancy, Research Funding. Roboz:Roche/Genentech: Consultancy; Eisai: Consultancy; Cellectis: Research Funding; Aphivena Therapeutics: Consultancy; Sandoz: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Jazz Pharmaceuticals: Consultancy; Sandoz: Consultancy; AbbVie: Consultancy; Celltrion: Consultancy; Cellectis: Research Funding; Eisai: Consultancy; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Pfizer: Consultancy; Celgene Corporation: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Bayer: Consultancy; Bayer: Consultancy; Roche/Genentech: Consultancy; Orsenix: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Orsenix: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy; Novartis: Consultancy; Aphivena Therapeutics: Consultancy; Argenx: Consultancy; AbbVie: Consultancy. Uy:GlycoMimetics: Consultancy; Curis: Consultancy. Stone:Fujifilm: Consultancy; Ono: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Agios: Consultancy, Research Funding; AbbVie: Consultancy; Argenx: Other: Data and Safety Monitoring Board; Celgene: Consultancy, Other: Data and Safety Monitoring Board, Steering Committee; Arog: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Jazz: Consultancy; Astellas: Consultancy; Merck: Consultancy; Pfizer: Consultancy; Sumitomo: Consultancy; Amgen: Consultancy; Cornerstone: Consultancy. Foran:Agios: Research Funding; Xencor, Inc.: Research Funding. Weisdorf:Seattle Genetics: Consultancy; Equillium: Consultancy; FATE: Consultancy; SL Behring: Consultancy; Pharmacyclics: Consultancy.

Abstract Multiple Myeloma (MM) is the most common indication for autologous hematopoietic stem cell transplantation (auto HCT). However, little information is available regarding the outcome of patients (pts) with the rarer immunoglobulin subtypes IgD and IgM, which represent 2% and 0.5%, respectively, of all MM cases. In addition, IgD MM has been reported previously to have a poorer prognosis, at least after conventional therapy. The CIBMTR conducted a retrospective analysis of MM pts transplanted between 1995–2005 to describe the characteristics and results of auto HCT in IgD (n=36) and IgM (n=11) among 3578 MM patients with auto HCT during this period. Median follow-up of survivors was 41 (range 2–130) months for pts with IgD and 58 (range 5–101) months for those with IgM MM. Among pts with IgD subtype, median age was 52 years (yrs), 67% were male, 36% had a creatinine >2 mg/L, 61% had Durie-Salmon stage III disease at diagnosis and 33% had Kappa Serum Light chain; the corresponding values for IgM pts were 58 yrs, 36%, 73% and 55% respectively. Prior to auto HCT, 75% of IgD pts were chemosensitive and 25% had received >2 lines of chemotherapy, while all IgM pts were chemosensitive and none had received more than 2 lines of prior therapy. Median time from diagnosis to auto HCT was 9 months in both subtypes. The most common conditioning regimen was singleagent melphalan, and all but 1 pt with IgD disease were grafted with blood stem cells. The small sample size precluded multivariate analysis for potential prognostic factors for outcome. Below table summarizes the post-auto HCT results in these pts contrasted with a reference pool of IgG and IgA MM receiving auto HCT in the same time period. Outcomes, probability (95% CI) IgD IgM IgG/IgA (n=36) (n=11) (n=1475) 100-day mortality, % 0 9 ( 0 – 32) 7 (5 – 8) Non MM deaths, % @ 1 yr 0 9 (0 – 32) 5 (4 – 7) @ 3 yrs 3 (0 – 13) 21 (2 – 51) 16 (14 – 18) Relapse/ Progression, % @ 1 yr 21 (9 – 37) 20 (2 – 49) 18 (16 – 20) @ 3 yrs 59 (41 – 76) 32 (8 – 64) 36 (34 – 39) Progression-free survival, % @ 1 yr 79 (63 – 91) 71 (41 – 93) 77 (74 – 79) @ 3 yrs 38 (21 – 56) 47 (17 – 78) 47 (44 – 50) Overall survival, % @ 1 yr 87 (74 – 97) 91 (68 – 100) 79 (77 – 85) @ 3 yrs 69 (51 – 84) 68 (36 – 93) 53 (50 – 57) No striking differences are apparent in the post auto HCT outcomes of patients with IgD and IgM MM. These results are also consistent with published outcomes of pts with IgD/ IgM MM (Wechaleker et al Ann Hematol. 2005 Feb; 84(2):115–7; Maisner et al Bone Marrow Transplant. 2008 Jan; 41(1):51–4).