ALBERT

Description: Background: Traditionally, pre-transplant conditioning regimen is given over 4-6 days before hematopoietic cell transplant (HCT). Delivering higher dose chemotherapy preparative regimen over a longer time period has not been tested previously. We hypothesized that the delivery of myeloablative dose of busulfan over a 3-week period may reduce toxicity and non-relapse mortality (NRM), without affecting relapse, and tested this in a prospective phase II study. Methods: Patients between 18 and 70 years of age with hematological malignancies and adequate organ function, with 8/8-HLA matched related or unrelated donor were eligible. They received a fixed dose of busulfan 80mg/m2 as outpatient on days -20 and -13. Then, fludarabine 40mg/m2 was given on days -6 to -2 followed by busulfan dosed to achieve target area under the curve (AUC) of 20,000 mol/min for the whole course based on pharmacokinetic studies. GVHD prophylaxis was cyclophosphamide (PTCy) 50mg/kg on days 3 and 4 and tacrolimus. Mycophenolate mofetil (MMF) was added to later unrelated donor recipients. All patients received standard supportive care. The primary endpoint was day 100 NRM. Results: We enrolled 52 patients with a median age of 62 (range, 39-69) years. Almost half (n=25, 48%) had AML or MDS and the other half (n=26, 50%) had had CML or MPD; 1 (2%) had multiple myeloma. Low, intermediate, high and very-high disease risk index (DRI) was present in 3 (6%), 34 (65%), 14 (27%) and 1 (2%). HCT-comorbidity index was 〉3 in 23 (44%) and 1-2 (n=23, 44%). A majority (n=32, 62%) had an unrelated donor. With a median follow up of 14 months (range, 3-23), NRM at day 100 was 1.9% (n=1) and 8% (95% CI, 0-15) at 1 year. Overall survival, progression-free survival and relapse at 1-year were 83% (95% CI, 73-95%), 78% (95% CI, 67-91%), and 14% (95% CI, 4-24%), respectively [Table]. There were no graft failures. The median time to neutrophil engraftment was 17 days (range, 13-33) and that of platelets (〉 20K/µL, n=45) was 24 days (range, 9-266). Day 100 grade II-IV and III-IV acute GVHD rates were 37% (95% CI, 23-50%) and 6% (95% CI, 0-12%), respectively; 1-year chronic GVHD and extensive chronic GVHD rates were 9% (95% CI, 0-17%) and 7% (95% CI, 0-14%), respectively. Overall survival at 1-year differed significantly among patients with low/intermediate DRI (94%; 87-100%) and those with high/very high DRI (53%; 31-91%), P=0.001. Conclusion: Myeloablative fractionated busulfan regimen with PTCy GVHD prophylaxis is feasible in older patients, has low incidence of severe acute GVHD, chronic GVHD, and NRM and results in promising overall survival. Table Disclosures Popat: Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; StemLine: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acrotech: Research Funding; Celgene: Research Funding. Ciurea:Miltenyi: Research Funding; Spectrum: Membership on an entity's Board of Directors or advisory committees; MolMed: Membership on an entity's Board of Directors or advisory committees; Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees, Other: stock holder. Kebriaei:Amgen: Research Funding; Pfizer: Honoraria; Jazz: Consultancy; Kite: Honoraria. Nieto:Astra-Zeneca: Research Funding; Affimed: Research Funding; Affimed: Consultancy; Novartis: Research Funding. Oran:AROG pharmaceuticals: Research Funding; Astex pharmaceuticals: Research Funding. Qazilbash:Autolous: Consultancy; Bioclinica: Consultancy; Speaker: Other: Speaker; Amgen: Other: Advisory Board. Molldrem:M. D. Anderson & Astellas Pharma: Other: Royalties. OffLabel Disclosure: Fludarabine & Busulfan as conditioning agent prior to transplant

Description: Disease relapse remains the major cause of treatment failure following hematopoietic transplantation for AML/MDS. A major goal is to develop more effective antileukemic regimens without excessive toxicity. Busulfan (Bu)-fludarabine (Flu) is a widely used preparative regimen. We demonstrated that targeting a relatively high busulfan systemic exposure pharmacokinetic (PK) dose adjustment was superior to fixed busulfan dosing. Clofarabine (Clo) has improved antileukemic activity compared to fludarabine. We previously reported a phase I/II study of different dosing combinations of busulfan with Flu and Clo; the best results were obtained with Bu with Flu 10 mg/m2 and Clo 30 mg/m2 daily for four daily doses. We performed a phase III randomized controlled trial to determine if Flu/Clo/Bu improved progression free survival compared to the Flu/Bu regimen. Busulfan was given with PK dose adjustment AUC 6000 mM x min for age

Description: Key Points Ex vivo fucosylation of cord blood cells improves their homing capacities, leading to faster neutrophil and platelet engraftments. This method is quick, safe, and does not require a GMP laboratory; therefore, it can be used widely.

Description: Introduction - Allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment for patients with myelofibrosis (MF). MF is stratified into various risk groups based on Dynamic International Prognostic scoring system (DIPSS plus), which determines the eventual prognosis of the disease at any time. Previous studies and expert opinion indicate that for patients with Intermediate-2 risk (INT-2) and High risk (HR) disease, HCT is a reasonable option. How applicable is this to all patients with MF and what are the barriers to doing a transplant are not known. We therefore reviewed medical records of all patients who were referred for HCT. The main purpose of this study was to determine the proportion of patients who underwent transplantation as well as to ascertain the major reasons why patients referred for transplantation did not receive it despite its reported benefit. Methods- This was a retrospective, single institution, observational study. We analyzed patients referred for HCT with a diagnosis of MF. One hundred and ninety-eight consecutive patients with a preliminary diagnosis of MF were seen at the stem cell transplantation and cellular therapy (SCTCT) clinic of MD Anderson cancer center (MDACC) from 1/1/2004 to 12/31/2012. Out of the 198 patients, 26 had a diagnosis other than MF and hence were excluded. We stratified the remaining patients according to their DIPSS plus score at the initial consult and also traced their progression. For the non-transplanted patient with HR and INT-2 DIPSS plus scores, the major reason for deferring transplant was retrieved from the chart. Results & Discussion- Out of 172 patients seen in the stem cell transplant clinic with MF, 70(41%) underwent transplantation and 102(59%) did not receive HCT. Of the 102 patients who did not undergo SCT, 72(70%) had INT-2 or HR disease at the initial consultation (transplant eligible). Of the remaining 30 patients with low risk or intermediate-1 risk disease, 7(23%) patients eventually progressed to INT-2 or HR disease and became transplant eligible. The median time from MF diagnosis to consultation for non-transplanted patients was 331days (11 months) (Range-0-8675). For patients with INT-2 and HR disease (79/102), the major reasons for not receiving a transplant (Figure) are patient choice (36/79; 46%), financial issues (23/79; 29%), comorbidities (9/79; 11%), lack of donor (7/79; 9%) and poor performance status (4/79; 5%). Patient choice of not pursuing transplant is understandable because there was limited data on efficacy of HCT for MF in early years. The most common insurance provider not covering transplantation was Medicare (20/23; 87%). The co-morbidities that precluded HCT were cardiopulmonary disease (4/9; 44%), liver dysfunction due to advanced disease (3/9; 33%) and other comorbidities (2/9; 22%). Of note 5/7 (72%) patients who were not transplanted due to lack of appropriate donor were non-Caucasian patients. Conclusion- Only 41% of patients referred for transplant with MF receive HCT. The major barriers to wider application and usage of HCT for MF were patient choice and lack of coverage by Medicare. Patient education, coverage by Medicare, use of alternative donors, and earlier transplant referrals can further increase the accessibility of transplantation and improve outcomes of patients with MF. Figure 1. Figure 1. Disclosures Alousi: Therakos, Inc: Research Funding.

Description: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the only curative treatment for myelodysplastic syndrome (MDS). Relapse, infections and graft-versus-host disease (GvHD) are the main causes of treatment failure. We compared the outcomes of patients receiving T cell depleted (TCD) grafts at Memorial Sloan-Kettering Cancer Center (MSKCC) with patients receiving unmodified grafts at MD Anderson Cancer Center (MDACC) for advanced MDS (RAEB-1 and 2). Adult patients transplanted between 2001 -2012 were included in this retrospective analysis. All recipients of TCD grafts (N=60) received myeloablative conditioning (MAC) and antithymocyte globulin (ATG) to prevent graft rejection. None of them received post-transplant GvHD prophylaxis. Of the 129 recipients of unmodified grafts, 87 received MAC and 42 reduced intensity conditioning (RIC); GvHD prophylaxis consisted of tacrolimus and mini-dose methotrexate in the majority of patients (N=113). ATG was given to all matched unrelated donor (MUD) recipients. Patients in the unmodified group had more therapy-related MDS (MDS-t), very poor risk cytogenetics by IPSS-R at diagnosis and bone marrow (BM) blast count 〉5% at transplant. Only the TCD group had mismatched donors (Table 1). Univariate analysis identified a lower incidence of grade II-IV acute GvHD in the TCD group with 100-day cumulative incidence (CI) of 13.3% vs. 34.1% in the unmodified group (p=0.031). There was no difference in grade III-IV acute GvHD with a 10% CI in both groups at day-100 (p=0.546). The incidence of chronic GvHD was lower in the TCD group with a CI at 3-yrs of 3.4% vs. 44.3% in the unmodified group (p 〈 0.001). The non-relapse mortality (NRM) in both groups was similar. CIs at day 100, 1yr, and 3 yrs in the TCD group were 8.3%, 20.2% and 32.7% vs. 12.4%, 22.5% and 28.1% in the unmodified group (p=0.628). Relapse was lower in the TCD group, with CI at 1 and 3 yrs of 8.5% and 15.5%, vs. 31.0% and 39.4% in the unmodified group (p=0.002). Since the unmodified recipients had worse disease characteristics, further analyses in patients with good/intermediate risk cytogenetic showed that the relapse incidence was similar between these subgroups, with 3-yr CIs of 7.9% in TCD vs. 18% in unmodified group (p=0.185). The most common causes of death in the TCD group were infections (32%) and relapse (28%), while in the unmodified group it was relapse (55%), GVHD (20%) and infections (13%). Considering the differences in disease characteristics between the groups, multivariate regression models were performed for relapse-free survival (RFS) and overall survival (OS) adjusting for MDS-t, high-risk cytogenetics at diagnosis and high blast count at HSCT. No significant differences were observed between the groups for RFS (HR=1.44, p=0.128) and OS (HR= 1.35, p=0.236) (Table 2). High-risk cytogenetics at diagnosis (very poor risk) was the only significant prognostic factor for RFS (HR=5.32, p

Description: In the present analyses, we sought to determine the impact of disease characteristics at diagnosis and at HSCT including pre-transplant MDS therapy and depth of response, stem cell source and intensity of conditioning regimen on disease outcomes after HSCT. Between 2000 and 2012, 291 MDS patients with a median age of 55 years (range, 18-71) were transplanted with a matched related donor (MRD, n=131), matched unrelated donor (MUD, n=114) or mismatched donors (MMD (n=46). The study cohort had high-risk features including 117 patients (40.2%) with therapy-related MDS (tx-MDS) and 78 (27.3%) with MK+. Histological subtype was RAEB-1 and -2 in 122 (41.9%) and CMML in 26 (8.9%) patients. Therapy prior to HSCT was chemotherapy only (chemo, n=81), hypomethylating agents only (HMA, n=100) and both (chemo+HMA, n=50). There were 74 untreated patients prior to HSCT. Of 74, 45 (60.8%) had tx-MDS, 48 (64.9%) had MRD and proceeded with HSCT with a median of 4.7 months. Among different therapy groups; histological subtype and disease status at HSCT, donor type and conditioning intensity were not different (Table 1). The median age among therapy groups were different with 54 vs. 57 and 59 observed in chemo, HMA and chemo+HMA (p

Description: Abstract 4200 Graft-vs.-Host Disease (GVHD) remains a common complication following matched sibling and unrelated donor hematopoietic cell transplantation (HCT). Standard GVHD prophylaxis calls for prolonged immune suppression, typically with a calcineurin-inhibitor. Recently, post-transplant cyclophosphamide (CY) has been studied as sole prophylaxis in matched related and unrelated bone marrow (BM) transplant recipients following an ablative conditioning regimen with busulfan (Bu) and CY and demonstrated comparable rates of acute GVHD and lower rates of chronic GVHD as traditional GVHD prophylaxis regimens. We recently conducted a phase II study of post-transplant CY following a reduced-intensity conditioning (RIC) regimen of Busulfan (Bu) and Fludaribine (Flu) in matched related and unrelated donor transplants and performed a matched-control analysis comparing their results with patients who received traditional GVHD prophylaxis with tacrolimus and mini-dose methotrexate (MTX) during the same time period. Forty-nine (49) patients were enrolled onto this study. They received Flu at a dose of 40mg/m2 over 1hour followed by intravenous Bu over 3 hours targeting a daily AUC of 4,000 microMol-min on days –6 to –3. Recipients of unrelated transplants received ATG on days –3 to –1 (total dose 4 mg/kg). CY was given as sole GVHD prophylaxis at a dose of 50 mg/kg on days +3 and +4. During the same period of time, 133 patients received a RIC regimen with intravenous Bu/Flu or Flu and melphalan (Mel) and received GVHD prophylaxis with tacrolimus plus mini-dose MTX (10mg/m2 on day +1, 5mg/m2on days +3, +6, +11). Unrelated donor transplants also received ATG. A computer generated algorithm was used to identify a comparable control group from our departmental database matching, in order of priority, on age, diagnosis, disease status, donor (matched-related versus unrelated) and graft source (PB versus BM). Matched controls (control group) were successfully identified for 37 study patients (Post-Cy group). Results: The median age for the Post- CY group and control group was 61 (range, 39–72) and 62 years (range, 37–72). Eight-one (81) % of patients in both groups had AML or MDS, 3% had ALL and 16% had NHL or CLL. Fifty-nine (59) % of patients in both groups had unrelated donors and received ATG in the conditioning. Disease status for the Post-CY and control groups respectively were CR1: 14 and 14%, CR2: 8 and 11%, 〉CR2: 38 and 32% and Primary Induction Failure / Untreated: 40 and 32%. Seventy (70) % of the post-CY group received BM versus 48% of the control group, whereas sex mismatching (Male donor for Female patient) occurred in 22% of the post-Cy and 8% of the control group. The cumulative incidence of grade II-IV acute GVHD and chronic GVHD in the post-CY and control groups were: 46% versus 19% (Hazard Ratio (HR): 2.8, 95% CI, 1.1–6.7; p=0.02) and 14% versus 21% (HR: 0.8, 95% CI, 0.2–2.6, p=0.7). Grades III/IV acute GVHD occurred in 14% (95% CI, 6–32) of the patients in the post-CY group whereas there were no cases of grade III/IV in the control group (p=0.02). Overall, progression-free and non-relapse mortality at 2-years are shown in the table below. Conclusion: Post-transplant CY following RIC is associated with higher rates of acute GVHD, with resultant trends for higher non-relapse mortality and lower overall survival when compared to tacrolimus and mini-dose MTX. The use of post-transplant CY as a sole GVHD prophylaxis regimen should be avoided following RIC transplant in matched-related and unrelated donors. Disclosures: Off Label Use: azacitidine: off-label use as maintenance therapy following allogeneic stem cell transplant for MDS/AML.

Description: A landmark study from Medical Research Council/Eastern Cooperative Oncology Group showed improved survival (∼53%) for patients allocated to sibling HCT versus either consolidation/maintenance chemotherapy or autologous HCT. Matched unrelated donors (MUD) are an option for patients without a SIB available and we retrospectively analyzed disease outcomes after SIB and MUD in adult ALL patients. Between 2001and 2012, 204 adult ALL patients with a median age of 36 years (range, 18-64) were transplanted with a SIB (n=112) or 8/8 MUD (n=92). Disease status at HCT was first or second complete remission and beyond (CR1, n=113, 55.5% and CR2+, n=91, 44.5%). Conditioning was myeloablative in 177 (86.8%) and reduced intensity (RIC) in 27 patients (13.2%). All but 2 patients received graft versus host disease (GVHD) immunosuppression with tacrolimus and methotrexate. Patient and disease characteristics including age, sex, histological subtypes and high risk disease features (WBC and cytogenetic classification at diagnosis), disease status at HCT and conditioning intensity were similar between SIB and MUD recipients. As expected, MUD patients had bone marrow (BM) as the stem cell source more commonly than SIB (69.6% vs. 7.1, p

Description: Background: As outcomes of haploidentical stem cell transplantation (HaploSCT) have improved, disease relapse represents the most common cause of treatment failure. Methods: We initiated a phase I clinical trial (clinicaltrials.gov NCT01904136) using peripheral blood-derived NK cells expanded ex vivo for 14 days with K562 antigen presenting cells expressing membrane-bound (mb) IL21 to prevent disease relapse after HaploSCT for patients with myeloid malignancies (AML,CML,MDS). We hypothesized that infusion of expanded and activated NK cells would compensate for the lower NK cell function in the early post-transplant period, and higher NK cell numbers would enhance anti-tumor effects of the graft. The primary endpoints were safety and determining the maximum tolerated dose (MTD). Patients were treated with a melphalan-based conditioning regimen (Figure). All patients had a primary bone marrow graft. NK cells were generated from peripheral blood mononuclear cells of the same donor obtained prior to marrow harvest and infused on days -2, +7 and on/after +28. The first infusion was with fresh and the other two were with cryopreserved NK cells. The dose escalation was planned in cohorts of 2 patients starting at 1x105/kg up to 1x109/kg or more if MTD will not be reached. Predictive NK alloreactivity and/or donor KIR B genotyping was preferred but not required to participate on study, however, was evaluated in all patients (Table). Results: Ten patients have been enrolled and treated to date. Of these, 8 patients were beyond Day+30 and were evaluated, 5 with AML (3 in CR1 with intermediate and 1 with high-risk cytogenetics, and 1 in CR2 FLT3+ with persistent MRD by flow cytometry) and 3 with CML (2 in second chronic phase, one with clonal evolution who failed multiple TKIs). The median age was 39 years (range 18-59). Four patients were males and 4 females. The NK cells dose escalation was as follows: 1x105/kg (N=2), 1x106/kg (N=3) and 1x107/kg (N=2). One patient was treated with 1x104/kg before full evaluation of 1x105/kg was completed. All patients achieved primary engraftment (100%). All patients except the one who received the lowest dose (1x104/kg) had sustained engraftment and 100% donor chimerism on Day 30 post-transplant. The median time to neutrophil engraftment was 18 days and to platelet engraftment was 26 days. The first patient had a mixed chimerism, developed secondary graft failure and concurrent parainfluenza pneumonia. He was re-transplanted with a different donor but died of treatment-related mortality (TRM). Of 7 patients evaluable for aGVHD, the maximum aGVHD grade was gr II in 4 patients. No gr III-IV aGVHD or cGVHD was observed. Only 3/7 patients had CMV reactivation (43% compared with 71% in retrospective data with the same treatment without NK cells), 2 requiring a brief period of treatment of approximately 1 month. None developed BK virus hemorrhagic cystitis. All patients achieved CR after transplant. One patient (#2) treated at 1x105/kg NK cell dose relapsed, received salvage treatment and is alive at last follow-up. All other patients are alive and in remission (N=6) after a median follow-up of 6 months (range 1-12.5). NK cell phenotype and function early post-transplant will be presented at the meeting. Conclusions: Doses up to 1x107/kg of ex vivo expanded NK cells using the mbIL-21 method can be safely administered after HaploSCT. Administration of these cells in this setting in not associated with a higher incidence of aGVHD. There was a low rate of viral reactivation, suggesting that the infused NK cells may provide antiviral activity. MTD has not been reached, the study is ongoing. Table. PT Nr Initials NK cell dose (/kg) Pt KIR Ligand Donor Donor KIR Ligand NK Allo-reactivity Donor KIR Haplotype # Cen-B/B KIR Score KIR Centromeric KIR2DS1 Outcome 1 RB 1x104 C2/C2, Bw4 Son C2, Bw4 No A/A 0 Neutral Cen-A/A - Died 2 FM 1x105 C1/C2, Bw4 Son C1, Bw4 No A/B 2 Better Cen-A/B - Relapsed +120 3 RG 1x105 C1/C2, Bw4 Daughter C1, C2, Bw4 No A/A 0 Neutral Cen-A/A - CR +374 4 GM 1x106 C1/C1, Bw4 Sister C1, C2, Bw4 Yes A/B 2 Better Cen-A/B - CR +168 5 DS 1x106 C1/C1 Brother C1, C2, Bw4 Yes A/A 0 Neutral Cen-A/A - CR +166 6 MH 1x107 C1/C2, Bw4 Sister C1, Bw4 No A/B 2 Best Cen-B/B + CR +91 7 JG 1x106 C1/C2, Bw4 Sister C1, C2, Bw4 No A/A 0 Neutral Cen-A/A - CR +35 8 DD 1x107 C1/C1, Bw4 Father C1, Bw4 No A/A 0 Neutral Cen-A/A - CR +87 9 RR 3x107 C1/C1 Brother C1, C2 Yes A/B 2 Better Cen-A, Cen/Tel-B - NE 10 JC 3x107 C2/C2, Bw4 Son C1/C2, Bw4 Yes A/B 2 Better Cen-A/B + NE Figure 1. Figure 1. Disclosures Lee: Intrexon: Equity Ownership; Ziopharm: Equity Ownership; Cyto-sen: Equity Ownership. Rezvani:Pharmacyclics: Research Funding.

Description: Allogeneic stem cell transplantation offers curative therapy for many patients (pts) with high-risk hematologic malignancies. Donor availability remains a major limitation for many pts. The introduction of high-dose post-transplant cyclophosphamide (PTCy) has significantly improved the outcomes of pts undergoing haploidentical (HAPLO) stem cell transplants. The choice between a HAPLO or a one-antigen HLA mismatched unrelated donor (9/10 MUD) for pts lacking an HLA-matched donor remains unclear. Methods: We conducted a prospective non-randomized phase 2 clinical trial with two parallel arms, HAPLO (n=60) and 9/10 MUD (n=46) transplants, for pts with advanced hematologic malignancies or aplastic anemia who lacked an HLA-matched unrelated donor type at 10 loci (HLA-A, -B, -C, -DRB1, and -DQB1) using a MEL-based reduced-intensity conditioning regimen. The regimen included a single intravenous dose of MEL 140 mg/m2 (day -7), thiotepa 5 mg/kg (day -6), and four daily IV doses of fludarabine 40 mg/m2 (day -5 to day -2) (FM140). Thiotepa was intermittently available and was replaced by total body irradiation at a dose of 2 Gy on day -1. Pts 〉55 years (yr) old or with significant comorbidities received a lower MEL dose (100 mg/m2) (FM100). All pts with CD20-positive lymphoma received rituximab (375 mg/m2) on days -13, -6, +1 and +8. GVHD prophylaxis consisted of PTCy 50 mg/kg on day +3 and +4, and tacrolimus and mycophenolate for 6 and 3 months (mo), respectively. The stem cell source was unmodified bone marrow for both arms. Results: Patient characteristics are shown in Table 1. The median follow-up duration was 24 mo in the HAPLO arm and 29 mo in the 9/10 MUD arm. The cumulative incidence (CI) of neutrophil (ANC) recovery at day 45 was 95% and 98% in the HAPLO and 9/10 MUD arm, respectively. The median time to ANC recovery was 18 days in both arms; the median time to platelet recovery was 25 days in the HAPLO arm and 28 days in the 9/10 MUD arm. Primary graft failure developed in two pts in the HAPLO arm (one due to anti-donor HLA antibodies) and one patient in the 9/10 MUD arm. One pt in both arms developed mixed donor chimerism at day 100; otherwise, all pts in both arms achieved full (〉95%) donor chimerism. Bone marrow was the graft source in all pts except 2 in the HAPLO arm and 8 in the 9/10 MUD arm who received a peripheral blood graft. The 1-yr overall and progression free survival were 70% and 60%, respectively, in the HAPLO arm (Fig. 1A) and 60% and 47%, respectively, in the 9/10 MUD arm (Fig. 1B). Day 100 CI of grade II-IV aGVHD and III-IV aGVHD were 28% and 3%, respectively, in the HAPLO arm versus 33% and 13%, respectively, in the 9/10 MUD arm; the 2-yr CI of chronic extensive GVHD was 13% and 14% in the two groups, respectively. The 1-yr CI of non-relapse mortality was 21% in the HAPLO arm and 31% in the 9/10 MUD arm, while the 1-yr relapse rate was 19% and 25% in the two groups, respectively. Conclusions: This study establishes PTCy, tacrolimus, and mycophenolate as an effective regimen for GVHD prevention in mismatched transplantation using both haploidentical and mismatched unrelated donor sources. Melphalan-based reduced-intensity conditioning is an effective regimen for a broad range of hematologic malignancies. Prospective randomized studies comparing haploidentical and unrelated donor sources are needed. Table 1. HAPLO (n=60) 9/10 MUD (n=46) Median Age, years (Range) 45 (20-63) 51 (20-64) Sex (M/F) 29/31 23/23 KPS ³90 53 (88%) 40 (87%) 3 10 (17%) 8 (17%) Disease Risk Index* Very high 5 (8%) 3 (7%) High 18 (30%) 15 (33%) Intermediate 29 (48%) 12 (26%) Low 8 (13%) 12 (26%) NA 0 4 (9%)** Conditioning Regimen FM100 20 (33) 18 (39%) FM140 40 (67%) 28 (61%) Diagnosis AML/MDS 33 (55%) 18 (39%) ALL 7 (11%) 5 (11%) Lymphoma 10 (17%) 13 (28%) Others 10 (17%) 10 (22%) Disease Stage Acute Leukemia CR1/CR2 24 (66%) 9 (56%) CR3 or higher/ CRpx 6 (17%) 5 (31%) Active disease 6 (17%) 2 (13%) Lymphoma CR 3 (30%) 8 (62%) PR 5 (50%) 3 (23%) Chemoresistant 2 (20%) 2 (15%) *Disease Risk Index by Armand et al; xCRp: Complete Remission with incomplete count recovery; **Patients had aplastic anemia. Figure 1. Figure 1. Disclosures Brammer: Celgene: Research Funding. Lee:Ziopharm: Equity Ownership; Cyto-Sen: Equity Ownership; Intrexon: Equity Ownership. Rezvani:Pharmacyclics: Research Funding. Alousi:Therakos, Inc: Research Funding.