ALBERT

Description: Background: Lower total CD34+ cell dose and increased HLA-mismatch are known predictors of engraftment failure and higher transplant related mortality (TRM) in cord blood (CB) recipients. To compensate for cell dose, double unit grafts (DUCBT) are commonly used in adult. However, in the majority of patients (pts), only one of the two CB units engrafts. Identification of the factors that predict which unit will engraft remains elusive, although increased recipient-donor HLA-matching and larger CD3+ cell dose have been associated with the predominating unit in a single center retrospective analysis (Ramirez et al, 2012). Historically, CB units are selected by maximizing matching at the HLA-A and -B antigen and -DRB1 allelic level. Evidence supports that matching at HLA-C appears to decrease TRM, and many clinicians incorporate HLA-C antigen matching into unit selection. It is unclear, however, if HLA-C matching predicts the engrafting unit in DUCBT. This study retrospective study evaluates whether HLA-C matching is associated with the winning CB unit. Design: Clinical data was reviewed from all pts with a hematologic malignancy receiving a DUCBT at Moffitt Cancer Center between November 13, 2009 and August 29, 2013. Chimerism studies identified the predominating unit (〉 65% single unit) between day 21 and day 28. Subsequent chimerism analyses performed at a median of day 100 confirmed unit predominance. Unit selection required intermediate resolution antigen match at HLA-A, -B, -C, and high resolution allele match at -DRB1. Units were a minimum of 4/8 matched to the patient and each other with a minimum cell dose of 1.5 x 107 total nucleated cell dose (TNC) /kg. Serology for donor specific antibodies against both units was negative. Results: Excluding 6 pts who were missing HLA-C typing on one or both CB units, 54 pts with hematologic malignancies (ALL=6, MDS/AML=29, Other=19) received chemotherapy and total body irradiation as part of a myeloablative conditioning (MAC) or reduced intensity conditioning (RIC) with or without thymoglobulin (ATG) followed by a DUCBT (MAC=14, RIC=23, RIC+ATG=17). Median age was 52 (range 22-69) years. Seven pts demonstrated persistent mixed chimerism in the myeloid and/or lymphoid cell lines beyond day 100. A total of 20 pts with available chimerism data received at least one CB unit matched to the recipient at HLA-C, with one patient excluded due to persistent mixed chimerism. Six pts received both CB units matched at HLA-C, but of the 13 pts receiving one matched and one mismatched unit, the HLA-C matched unit was the engrafting unit 69% (9/13) of the time. Comparing similar HLA mispairings, a matched unit engrafted over a mis-matched unit at HLA-A 50% (5/10) of the time, at HLA-B 38% (5/13) of the time, and at HLA-DRB1 50% (3/6) of the time. TNC dose (larger vs smaller with a required difference of at least 0.03 x 107 TNC/kg), order of infusion (first vs second unit), and overall CB unit HLA matching (4/8-8/8), were assessed as potential predictors for engraftment. Of evaluable patients, the CB unit with the larger TNC engrafted 44% (16/36) of the time, and the first unit infused was the engrafting unit 54% (21/39) of the time. In patients with an unequal overall match grade between the CB units, the better HLA-matched CB unit engrafted 64% (14/22) of the time. Survival analysis of all pts revealed that those who received at least one CB unit antigen matched at HLA-C (n=20) had a 100 day and 1 year overall survival (OS) of 85% (95% Confidence Interval(CI): 67–97%) and 55% (95% CI: 33–75), respectively, whereas pts receiving two HLA-C mismatched CB units (n=34), 100 day OS was 62% (95% CI: 45–77) with 1 year OS 44% (95% CI: 28–61) (Fig 1). Conclusion: HLA-C antigen matching appears to help predict the winning unit in settings of HLA-match disparity and DUCBT. Confirmation in a larger population of DUCBT recipients is necessary. To date, the effects of HLA matching and other variables influencing engraftment have been predominately evaluated in recipients of single unit transplants and studies in DUCBT have been limited. Further investigation assessing HLA matching as well as donor-donor interactions is best served through a multicenter data resource. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Background: Approximately 60 - 80% of AML patients achieve a complete remission [CR] with one or two cycles of induction chemotherapy, leaving many patients with refractory AML [PIF]. Unfortunately, the majority of patients in CR1 ultimately relapse. With salvage therapy, only 30-50% achieve CR2. Those with PIF or relapsed AML have shortened survival and few therapeutic options. Risk stratification is primarily based on karyotype, however other factors including age, initial white blood cell count, secondary AML and mutational status are also utilized to determine prognosis. HCT is an effective option for treatment of AML with intermediate/high risk features in CR1. It has also been utilized in refractory or relapsed disease. Advances in HCT over the last decade have improved overall survival (OS) and extended this option to older patients. Our aim is to characterize outcomes after HCT for AML patients who are not in CR1. Methods: We analyzed 136 AML patients who were not in CR1 at the time of HCT from 2004 - 2013. The conditioning regimen was fludarabine and myeloablative doses of PK targeted busulfan. IWG AML response criteria were used to define disease status at the time of transplant. Cytogenetic risk was based on the NCCN AML guidelines. OS is defined as the time from HCT until the time of death from any cause. Disease free survival (DFS) is defined as the time from HCT to the time of relapse or death from any cause. Results: Disease status consisted of 74 (54.4%) in CR2, 6 (4.4%) in CR3 or beyond, 27 (18.9%) were PIF, 21 (15.4%) with relapsed AML (REL) that was treated but still present at time of transplant, and 8 (5.7%) who received either no treatment or a hypomethylating agent (HMA). Median age was 52.0 (21.8 - 72.5) years, and 80 (59%) were male. Time from most recent treatment to HCT was 〈 1 month in 8 (5.8%), 1-3 months in 75 (55.8%), 〉3 months in 50 (36.8%) and not applicable in 3. Ninety-six (70.6%) had de novo AML, while 40 (29.4%) had secondary AML. Cytogenetic risk was favorable in 32 (23.5%), intermediate in 57 (42%), poor in 40 (29.4%) and unknown in 7 (5.1%). Graft-versus-host disease prophylaxis was tacrolimus with methotrexate or sirolimus, or mycophenolate mofetil. Donors included 41 (30.2%) matched related, 2 (1.4%) mismatched related, 65 (47.8%) matched unrelated and 28 (20.6%) mismatched unrelated donors. Peripheral blood stem cells were used in 97.2% of cases. Two year OS, DFS, cumulative incidence (CI) of relapse and CI-NRM for all patients was 45.3%, 35.2%, 47.1% and 18.2%, respectively. Two-year DFS stratified by disease status at time of HCT was 41.9%, 33.3%, 25.9%, 33.3% and 12.5% in CR2, CR3 or beyond, PIF, REL and HMA, respectively(p=0.011 for CR2 vs HMA) (Figure 1). Two-year DFS stratified by cytogenetic risk was 43.8%, 31.6%, 37.1% and 14.3% in favorable, intermediate, poor and unknown, respectively (p〉0.05) (Figure2). CI-Rel stratified by disease status was 43.2%, 16.7%, 66.7%, 42.9% and 50% in CR2, CR3 or greater, PIF, REL and HMA, respectively (Figure 3). Conclusions: We analyzed 136 AML patients after undergoing HST outside of CR1 and the cumulative incidence of relapse at two years was 47%. Relapse was highest in those with primary induction failure or residual disease after either no or low intensity therapy. These data suggest that patients with active disease at the time of transplant fare worse than those who are transplanted in remission, highlighting the importance of effective upfront therapies in order to obtain the maximum potential benefit from HCT. Cytogenetic risk stratification did not significantly impact outcomes, although those with favorable risk cytogenetics trend towards higher 2-year DFS vs those with intermediate or poor-risk disease. Trials looking at the impact of maintenance therapy post-transplant may be valuable in this patient population. Table 1. Disease Status @ HSCT CR2 CR3 or beyond PIF RES HMA/untreated 2 years 41.9% (30.6 - 52.8) 33.3% (4.6 - 67.6) 25.9% (11.5 - 43.1) 33.3% (14.9 - 53.1) 12.5% (0.7 - 42.3) Table 2. Cytogenetic Risk Group Favorable Intermediate Unfavorable Unknown 2 years 43.8% (26.5 - 59.8) 31.6% (20.1 - 43.7) 37.1% (22.5 - 51.8) 14.3% (0.7 - 46.5) Table 3. Cumulative Incidence of Relapse CR2 (1) CR3 or beyond (2) PIF (3) REL (4) HMA/untreated (5) 2 years 43.2% (32.2 - 54.6) 16.7% (0.0 - 53.5) 66.7% (48.1 - 82.9) 42.9% (23.0 - 64.0) 50.0% (18.1 - 81.9) Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Sweet: Novartis Pharmaceuticals: Speakers Bureau; Ariad Pharmaceuticals: Consultancy, Speakers Bureau; Karyopharm Therapeutics Inc: Research Funding; Incyte: Research Funding. Lancet:Celgene: Consultancy, Research Funding; Seattle Genetics: Consultancy; Boehringer-Ingelheim: Consultancy; Pfizer: Research Funding; Kalo-Bios: Consultancy; Amgen: Consultancy. Perkins:PDL Biopharma: Research Funding. Field:PDL Biopharma: Research Funding.

Description: Introduction: Central nervous system (CNS) involvement by plasma cell dyscrasias (PCD) is uncommon but poses significant clinical challenges and has a dismal prognosis. Lumbar puncture (LP) is typically performed only for patients with neurologic signs or symptoms and data on patients with CNS involvement are rather scarce. Here, we report a retrospective single institution review of clinicopathological features and treatment outcomes in the setting of cerebrospinal fluid (CSF) involvement by PCD. Methods: We identified consecutive patients with plasma cell disorders who had abnormal cytology or flow cytometry results in the CSF in the Department of Hematopathology database at Moffitt Cancer Center from 1997 to 2014. Cytology slides [Wright-Giemsa (WG) and Papanicolaou (Pap) stained preparations] and the corresponding flow cytometry were reviewed to confirm the diagnosis. Four-color flow cytometry was performed using antibodies against CD38, CD138, CD56, CD117, CD19, and cytoplasmic kappa and lambda light chains, withadditional markers added when necessary. Clinical variables were abstracted from the patient medical records. Overall survival was estimated from the time CSF involvement was identified using the Kaplan-Meier method. Results: Sixty-seven Pap-stained cytology smeas/cytospins and WG stained cytospins from 65 patients who underwent LP for clinical suspicion of CSF involvement were reviewed. Flow cytometry was preformed on 48 cases positive for atypical plasma cells by cytology. Sixteen of 67 (23.9%) were suspicious or diagnostic for PCD (median age of 58 years (range 44 – 75), 56% were male). However, only 4 of 16 cases (25%) were diagnosed as PCD by cytology without additional flow cytometry study. Median tumor load of PCD by flow cytometry was 81% (range 4 - 99%). PCD included 14 patients (88%) with multiple myeloma [MM; 1 patient progressed to secondary plasma cell leukemia (PCL)], 1 with primary PCL, and 1 with Waldenström macroglobulinemia (Neel-Bing syndrome). Of the 14 MM patients, 57% had high-risk disease by cytogenetics/FISH, and immunophenotypes were IgA (50%), IgG (29%), and light chain (21%). All MM patients had Durie-Salmon stage 3 disease. Median number of prior therapies was 2 (1-4), and 44% received stem cell transplant prior to CSF involvement. Median time from diagnosis to CSF involvement was 23 (range, 6 – 78) months. Presenting symptoms included diplopia/vision loss (31%), headache (25%), and leg weakness (cauda equina/cord compression) (19%). Two patients presented with gross orbital involvement and new/enlarging scalp lesions. On radiologic imaging, 5 (31%) had leptomeningeal, 4 (25%) had epi- or extra-dural, and 2 (13%) had dural enhancement/lesions. None had CSF involvement at the time of initial PCD diagnosis. Treatment included intrathecal chemotherapy (methotrexate, cytarabine or triple regimen; 86%), radiation therapy (including whole brain, craniospinal, radiosurgery or involved field; 63%) and systemic chemotherapy (65%). One patient did not receive treatment due to poor performance status. For 5 patients who had repeat CSF analyses, only one had no evidence of disease on cytology but flow cytometry remained positive. Six-month overall survival rate was 20.2% (95% CI 4.4 – 43.5). At the time of data review, only 2 patients were alive. Conclusions: CSF involvement by PCD carries extremely limited prognosis and represents advanced stage of the disease. Patients may be treated with systemic therapy as well as CNS-directed therapy, though the outcomes are dismal. Careful assessment of patients’ neurologic symptoms and low threshold for performing LP is required for early detection of CSF involvement. Application of flow cytometry appears to be a useful tool in the diagnosis of CSF involvement by PCD; improving sensitivity and specificity over cytology alone, particularly when the tumor load is low or cytologically equivocal for atypical plasma cells. Further research is needed to improve the outcomes of these patients. Disclosures No relevant conflicts of interest to declare.

Description: Background: Multiple myeloma remains incurable despite impressive array of available novel agents and therapeutic strategies. Allogeneic hematopoietic cell transplantation (HCT) remains the only potentially curative option for patients with multiple myeloma but it is limited by its toxicities. We previously reported initial result of a phase 2 study of upfront allogeneic HCT in myeloma patients achieving at least very good partial response (VGPR) after initial therapy (Nishihori, et al. ASH 2013 abstract 3390) and here we report more mature results after a median follow up of 3 years. Methods: Twenty seven myeloma patients received allogeneic HCT between 01/2010 and 02/2015 at Moffitt Cancer Center (NCT 00948922). Eligible patients were age ≤ 60, achieving first ≥ VGPR or complete response (CR), and have 8/8 HLA-matched related or unrelated donors. Conditioning regimen consisted of fludarabine 30 mg/m2 for 4 days (days -6, -5, -4, and -3) and melphalan 70 mg/m2 for 2 days (days -4 and -3) followed by a single dose of bortezomib 1.3 mg/m2 on day -3 (Flu/Mel/Vel regimen). GVHD prophylaxis was initially left to the discretion of physicians but later modified to only tacrolimus/methotrexate. No maintenance therapy was prescribed after allogeneic HCT. Results: The median age at transplant was 50 (range, 25-58) years. Disease status at the time of allogeneic HCT was VGPR (n=17: 63%) and CR/stringent CR (n=10: 37%). All patients received unmanipulated peripheral blood stem cell grafts from HLA-matched related donors (n=14) or HLA-matched unrelated donors (n=13). Graft-versus-host disease (GVHD) prophylaxis was tacrolimus plus either methotrexate (n=19: 70%), or mycophenolate mofetil (n=4), or sirolimus (n=4). All patients achieved neutrophil engraftment with a median of 15 (range, 11-19) days. Platelet engraftment was achieved with a median of 17 (range, 13 - 35) days and 2 patients did not recover platelets. The cumulative incidences of grades II-IV and grades III-IV acute GVHD at day 100 were 63.6% (95% confidence interval (CI): 43.1-81.1) and 19.6% (95%CI: 5.4-39.9), respectively. The cumulative incidence of moderate to severe chronic GVHD was 56.4% (95%CI: 36.3-75.5) at 1-year. The cumulative incidences of transplant-related mortality at day 100, 1 year and 2 years were 7.4% (95%CI: 0.8-20.0), 11.1% (95%CI: 2.7-25.4), and 11.1% (95%CI: 2.7-25.4), respectively. Progression-free survival estimates at 1, 2, and 3 years were 74.1% (95%CI: 53.2-86.7), 65.1% (95%CI: 43.3-80.2), and 65.1% (95%CI: 49.9-87.5), respectively. With a median follow up of 39 months for surviving patients, overall survival estimates at 1, 2 and 3 years were 85% (95%CI: 64.9-94.1), 75.4% (95%CI: 52.6-88.3), and 69.1% (95%CI: 53.8-93.5), respectively. Conclusions: The results of the this phase 2 trial of upfront allogeneic HCT with fludarabine/melphalan/bortezomib (Flu/Mel/Vel) conditioning are promising and provide the rationale for reasonable potentially curative option to younger and fit patients who are eligible for upfront intensive consolidation strategy. This approach may be potentially valuable for those with high-risk myeloma and a multicenter study is currently being conducted (BMT CTN protocol 1302:NCT02440464). Disclosures Nishihori: Novartis: Research Funding; Signal Genetics: Research Funding. Baz:Takeda/Millennium: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Novartis: Research Funding; Karyopharm: Research Funding; Bristol-Myers Squibb: Research Funding; Signal Genetics: Research Funding. Shain:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen/Onyx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Signal Genetics: Research Funding; Takeda/Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Alsina:Signal Genetics: Consultancy; Novartis: Research Funding; Takeda/Millennium: Research Funding; Amgen/Onyx: Consultancy, Speakers Bureau.

Description: Background The use of allogeneic hematopoietic cell transplantation (HCT) in multiple myeloma (MM) remains controversial but the role of allogeneic HCT for consolidation of initial response in the era of novel agents has not been defined. Therefore, we conducted a phase 2 study of allogeneic HCT in MM patients achieving at least very good partial response (VGPR) after initial therapy. Methods Seventeen MM patients with first VGPR or complete remission (CR) received allogeneic HCT between 01/2010 and 04/2013 at Moffitt Cancer Center (NCT 00948922). Eligible patients were age ≤ 60, achieving ≥ VGPR, and have suitable HLA-matched donors. Six patients received bortezomib plus lenalidomide induction, 7 received bortezomib-based, and 4 received lenalidomide-based induction. Three patients (18%) underwent autologous HCT with melphalan plus bortezomib conditioning (melphalan 100 mg/m2 for 2 days followed by bortezomib 1.3 mg/m2) following induction therapies in order to achieve further cytoreduction. Conditioning regimen before allogeneic HCT consisted of fludarabine 30 mg/m2 for 4 days and melphalan 70 mg/m2 for 2 days followed by a single dose of bortezomib 1.3 mg/m2 (Flu/Mel/Vel). GVHD prophylaxis was tacrolimus plus either methotrexate (n=9), or mycophenolate mofetil (n=4), or sirolimus (n=4). No maintenance therapy was prescribed after allogeneic HCT. Results The median age at transplant was 51 (25 – 57) years and the median time from initial therapy to transplant was 236 (126 – 418) days. Seven patients (41%) have high-risk cytogenetics/FISH. The median number of prior therapy was 1. Disease status at the time of allogeneic HCT was VGPR (n=8), CR (n=3), or stringent CR (n=6). All patients received unmanipulated peripheral blood stem cell grafts from HLA-matched sibling donors (n=7) or 8/8 HLA-matched unrelated donors (n=10). All patients achieved neutrophil engraftment with a median of 14 (11 - 18) days and platelet engraftment with a median of 17 (13 - 21) days. All patients established stable donor cell chimerism. Best responses after allogeneic HCT were CR (n=2), sCR (n=13), and disease progression (n=2). The 2-year progression-free survival estimate is 80% (95%CI: 51 – 98) for standard-risk group and 51% (95%CI: 15 – 87) for high-risk, respectively. With a median follow up of 18 (3 - 43) months for surviving patients, the 2-year overall survival estimate is 88% (95%CI: 68 – 99). The cumulative incidence of non-relapse mortality was 6% (95%CI: 0.0 – 22) at 100 days and 13% (95%CI: 1 – 34) at 1 year, respectively. The cumulative incidence of grades 2-4 acute GVHD at day 100 was 41% (95% CI: 20 – 65) and the cumulative incidence of moderate to severe chronic GVHD at 1 year was 8.0% (95% CI: 0.0 – 29). Conclusions These results indicate that allogeneic HCT for MM in VGPR or CR as consolidation achieves favorable disease control. The study is ongoing to assess long-term safety of this modality. A multicenter trial is planned to evaluate the utility of allogeneic HCT in high-risk MM. Overall Survival Months Disclosures: Off Label Use: bortezomib - transplant conditioning. Alsina:Millennium: Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Description: Background: High-dose melphalan followed by autologous hematopoietic cell transplantation (HCT) remains the integral component of multiple myeloma (MM) therapy in the era of novel agents. We published our prior study with the use of high-dose melphalan + bortezomib (Mel/Vel) conditioning regimen for tandem transplants in refractory MM patients (Nishihori, et al. Br J Haematol 2012). We designed a phase 2 trial using MelVel conditioning followed by autologous HCT in patients with newly diagnosed chemosensitive MM (NCT 00948922). Methods: Sixty seven newly diagnosed MM patients who achieved ≥ partial response (PR) to induction therapy with ≤grade 1 peripheral neuropathy (PN) were enrolled from 12/2009 to 06/2014. Patients received high-dose melphalan at 100 mg/m2 IV for 2 days, immediately followed by 1 dose of bortezomib at 1.3 mg/m2 (Mel/Vel conditioning). Maintenance therapy was not prescribed by design. The protocol later was modified to include maintenance bortezomib subcutaneously (started at 3 months after HCT) at 1.3 mg/m2 weekly x4, every 8 weeks, for a total of 6 cycles. Progression-free and overall survival (PFS and OS) estimates were calculated using Kaplan-Meier method. Results: A total of 67 patients received autologous HCT. The median age was 58 (25 - 73) years with the following disease characteristics: Durie-Salmon stage, 3A (72%) and 3B (10%); IgG (55%), IgA (21%), IgD (1%), and light chain (22%). High-risk cytogenetics/FISH were seen in 28% of patients. The median beta-2 microglobulin was 3.3 (range, 1.3 – 34.8). Induction regimens were bortezomib-based in 39%, lenalidomide-based in 19% and, both bortezomib and lenalidomide in 42%. Median time from initiation of induction to HCT was 204 days (range, 101 - 664). Responses prior to HCT were stringent CR (sCR) 21%, CR 12%, very good partial response (VGPR) 34%, and PR 33%. Neutrophil engraftment was achieved after a median of 11 days (range, 10 – 14) and platelet engraftment occurred after a median of 15 days (range, 11 – 22). Median CD34 cell dose was 3.8 x 106/kg (range, 2 – 20.08). Responses at 3 months after HCT (in 64 evaluable patients) were sCR 47%, CR 14%, VGPR 20%, PR 16% and progressive disease 3%. Bortezomib maintenance was prescribed to 31 patients (46%). Prevalence of grade 1 PN before (n=67) and at 3 months (n=64) after HCT were 37% and 38%, respectively. Two patients withdrew consent to initiate maintenance and 1 patient was unable to initiate maintenance due to grade 1 PN (baseline PN of 0). At the time of review, a median number of maintenance delivered was 4 (range, 1-6) and only one patient required dose reduction. The 2-year PFS and OS estimates are 62% (95% CI 0.47 – 0.75) and 90% (95% CI 0.80 – 0.97) with a median follow-up of 21 months (range, 2 – 54). The 1-year PFS estimates were 85% (95% CI 0.65 – 0.97) for bortezomib maintenance vs. 81% (95% CI 0.66 – 0.92) for no maintenance (p=0.6). There were no significant differences in PFS or OS stratified by cytogenetic/FISH risk status. There was no transplant related mortality. Conclusions: The combination of bortezomib and high-dose melphalan (Mel/Vel) as conditioning regimen for autologous HCT is well tolerated and appears to improve responses after HCT. Weekly x4 post HCT bortezomib maintenance given every 8 weeks appears to be well tolerated and is a promising strategy for eligible patients. Longer follow up is required to assess the benefit of post HCT maintenance strategy. Disclosures Baz: Millennium: Research Funding. Alsina:Millennium: Consultancy, Research Funding.

Description: HCT is the only known curative treatment for MDS. Treatment with the DNA methyltransferase inhibitor 5-azacitidine (aza) can slow leukemic progression and has been utilized prior to HCT for both tumor debulking and to provide stabilization of the disease during the pre-allograft period. To discern the impact of pretransplant aza treatment on HCT outcomes, we retrospectively analyzed 132 patients (pts) according to pretransplant aza exposure. Patients included those who had a diagnosis of MDS or CMML at any time point in the course of their disease who subsequently received a HCT from a HLA-compatible donor. Eligible patients proceeded to transplant if they had adverse disease features such as elevated IPSS risk, treatment related MDS, progression of disease or refractory disease. Consecutive patients referred for HCT between July 2004 and July 2009 were evaluated. Seventy percent of pts with an identified donor proceeded to HCT. All received a myeloablative HCT using fludarabine and IV-busulfan [targeted to a specific AUC of 3500, 5300, 6000 or 7500]. Graft versus host disease prophylaxis was with tacrolimus plus methotrexate or sirolimus or mycophenolate mofetil. Only those with mismatched donors received antithymocyte globulin. The median age of the 64 allograft pts not receiving preHCT aza (No AZA group) was 56.8 (24.8 –73.5) years (yrs). Thirty-seven (58%) pts were older than 55 yrs. At diagnosis, IPSS risk was Low (n=4), Int-1 (n=23), Int-2 (n=13), High (n=5), not evaluable (n=4) (NE), AML (n=16) and CMML (n=9). Seventeen had treatment related MDS (tMDS) and 18 had AML at one time. Donors included 24 sibling donors (MRD), 29 matched unrelated donors (MUD) and 11 mismatched unrelated donors (mMUD). Median follow-up is 66.2 months (29.7 – 105.7 months). Sixty-eight pts received a median of four (1-12) cycles of aza prior to HCT (YES AZA group). The median age was 57.3 (25.6 – 73.8) yrs. Thirty-nine pts (57%) were older than 55 yrs. At diagnosis, IPSS risk was Low (n=3), Int-1 (n=21), Int-2 (n=21), High (n=12), NE (n=2), AML (n=2) and CMML (n=7). Eighteen had tMDS and 10 had AML at one point. Donors included MRD (n=32), MUD (n=31) and mMUD (n=5). Median follow-up is 53.8 months (24.1 – 103.2 months). Prior to transplant the number of marrow blasts in the No-AZA vs Yes-AZA was: 20% (n=2 vs 3) and CMML (n=4 vs 6). All patients engrafted with no difference in engraftment rates or toxicities between the two groups. Additionally, cumulative incidence of non-relapse mortality and relapse rates at 1 yr/ 3 yrs were similar [NRM: No AZA 20.5/ 37.4% vs Yes AZA 20.7/ 23.9 %; REL: 34.2/ 37.5% vs 26.4/ 32.4%]. At 3 years, the RFS and OS suggest improvement with pretransplant AZA but do not reach statistical significance [RFS: No AZA 26% vs Yes AZA 44.1%; p = 0.14; OS: 30.9% vs 51.4%; p=0.15]. Utilization of pre-HCT 5-azaciticidine is a feasible strategy and doesn’t appear to have any negative impact on HCT outcomes. Given the disease control facilitated by aza it should be offered to patients with high risk MDS coming to transplant. Disclosures: Field: Celgene: Research Funding. Alsina:Millennium: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Lancet:Celgene: Research Funding. List:Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau.