ALBERT

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: INTRODUCTION More active high-dose regimens are needed for non-Hodgkin’s (NHL) and Hodgkin’s lymphomas (HL), where standard BEAM offers poor results in refractory or poor-risk relapsed tumors. We previously developed a regimen of infusional gemcitabine with busulfan and melphalan (Gem/Bu/Mel), exploiting the synergy between gemcitabine and alkylators based on inhibition of DNA damage repair. Gem/Bu/Mel was safe and highly active against refractory lymphomas (Nieto, BBMT 2012). To further increase its activity we combined it in preclinical experiments with SAHA, which induces relaxation of the chromatin and renders DNA more accessible to DNA-targeting agents. Concurrent exposure to SAHA and Gem/Bu/Mel resulted in markedly increased apoptosis and cytotoxicity in refractory B- and T-NHL lines, with increased PARP1 cleavage and γ-H2AX reflecting increased DNA damage (Valdez, Exp Hematol 2012). SAHA has a dose-response effect in refractory lymphoma lines up to clinically achievable levels with doses of 1,000 mg, higher than its usual dose. We wished to clinically study the concurrent combination of SAHA and Gem/Bu/Mel in refractory NHL and HL. Methods Patients ages 12-65 with refractory lymphomas and adequate end-organ function were eligible for this dose-finding study of SAHA combined with Gem/Bu/Mel. SAHA was given on days -8 to -3 at 200-1,000 mg PO daily (levels 1-11), preceding all chemotherapy. Gemcitabine was given as a loading dose of 75 mg/m2 followed by infusion at a fixed dose rate of 10 mg/m2/min over 3.5 (levels 1-5), 4 (level 6) or 4.5 hours (levels 7-11) on days -8 and -3. Each gemcitabine dose was immediately followed by the corresponding dose of busulfan or melphalan. After a test dose on day -10, busulfan was given from days-8 to -5 targeting a daily AUC of 4,000. Melphalan was infused at 60 mg/m2/day on days -3 and -2. ASCT was on day 0. Patients with CD20+ tumors received rituximab (375 mg/m2) on days +1 and +8. Dose limiting toxicities (DLT) were defined as any G4-5 nonhematological organ toxicity, or as G3 skin or G3 mucositis lasting 〉3 days at peak severity. Dose escalation followed a Bayesian design targeting a maximal DLT probability of 20%. Results Between 10/11 and 6/13, 66 patients were enrolled with DLCL, HL and T-NHL (Table 1). SAHA was escalated up to 1,000 mg PO daily, combined with full doses of Gem/Bu/Mel without encountering DLTs. There were no treatment-related deaths. The toxicity profile was manageable, including mucositis (48% G2, 31% G3), skin (11% G2, 3% G3), self-limited transaminase elevation (30% G2, 6% G3), and self-limited elevation of bilirubin not associated to VOD (22% G2, 16% G3). There were no cardiac, pulmonary, renal or CNS toxicities. There was no QT prolongation detected after SAHA. Neutrophils and platelets engrafted promptly at median days +10 (range, 8-13) and +12 (range, 8-55), respectively. This toxicity profile is undistinguishable from the one we previously described with Gem/Bu/Mel. Activity and patient outcomes at median follow-up of 8 months (1-23) are shown on Table 2 and Figures: Conclusions Concurrent administration of SAHA with high-dose GemBuMel is feasible up to a daily dose of SAHA of 1,000 mg, with no increased toxicities compared to Gem/Bu/Mel alone. Early results indicate that SAHA/Gem/Bu/Mel is highly active in refractory or poor-risk relapsed HL and DLCL and warrants further study in earlier disease stages. Longer follow-up is needed to confirm these findings. Disclosures: Nieto: Otsuka Pharmaceuticals: Research Funding. Off Label Use: Vorinostat not approved for DLCL or Hodgkin's lymphoma. Qazilbash:Otsuka Pharmaceuticals: Research Funding. Andersson:Otsuka Pharmaceuticals: Research Funding.

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: Abstract 2013 Allogeneic stem cell transplantation (ASCT) with T-cell depleted (TCD) allograft has been used to decrease the risk of graft-versus-host disease (GVHD). How outcomes of ASCT with TCD grafts compares to transplant with unmodified grafts in the context of ablative, reduced toxicity conditioning with busulfan /fludarabine is unknown. We sought to compare ASCT with and without TCD grafts, by studying the outcomes of pts with acute myeloid leukemia (AML) in first complete remission (CR1) who had TCD allografts at Memorial Sloan Kettering Cancer Center (MSKCC) with those who had unmodified allografts at MD Anderson Cancer Center (MDACC). Transplants at MSKCC (N=115) and MDACC (N=181) were performed between 2001 and 2010. Preparative regimens at MSKCC included: 1) Hyperfractionated total body irradiation (HFTBI) 1375 cGy over 4 days, thiotepa 5 mg/kg/day × 2 days & fludarabine 25 mg/m2/day × 5 days (n=29); 2) HFTBI 1375 cGy over 4 days, thiotepa 5 mg/kg/day × 2 days & cyclophosphamide 60 mg/kg/day × 2 days (n=25); or 3) busulfan 0.8 mg/kg intravenously every 6 hours for 10 doses(n=42) or 12 doses (n=19), melphalan 70 mg/m2/day × 2 days & fludarabine 25 mg/m2/day × 5 days (total n=61). Peripheral blood (PB) grafts underwent CD34+ cell selection using the ISOLEX 300i system, followed by sheep red blood cell (sRBC)-rosette depletion (n=85); or CD34+ cell selection using the CliniMACS system alone (n=22). Bone marrow (BM) grafts were T cell depleted by sequential soybean lectin agglutination and sRBC-rosette depletion (n=8). No additional GVHD prophylaxis was administered at MSKCC. Fludarabine 40 mg/m2 and busulfan 130 mg/m2 intravenously once daily for 4 days were used for conditioning at MDACC, with tacrolimus and mini-methotrexate for GVHD prophylaxis. Pts with unrelated or HLA-mismatched donors treated at MDACC and MSKCC received equine (total 60 mg/kg) or rabbit (total 2.5–5 mg/kg) anti-thymocyte globulin. Cytogenetic risk stratification considered complex cytogenetics, -5, -5q, -7, -7q, 11q23 aberrations, inv(3), t(3;3), t(6;9), and t(9;22) as poor risk. Pt characteristics and outcomes are summarized in the Table. TCD recipients were more likely to be older, receive a mismatch transplant, and have PBSC used as a graft source. Overall, only one pt, who had received an unmodified graft, experienced primary graft failure. Eleven (10%) and 33 (18%) pts experienced grade ≥2 acute GVHD within 100 days after transplants with TCD and unmodified grafts, respectively (p=0.05). Three-year relapse-free and overall survival rates were 58% and 57% in pts who received TCD grafts, and 60% and 66% in pts who received unmodified grafts (P=NS; Figure). There was a trend towards lower early non-relapse mortality among pts who received unmodified grafts (3% vs. 8% at 100 days, p=0.07). Of age, sex, secondary disease, risk status, donor, and graft type, secondary AML was the only risk factor found to significantly influence overall survival (HR: 1.7, 95% CI: 1.1–2.8). Survival outcomes were still comparable between recipients of TCD and unmodified grafts after adjusting for secondary AML. None of these factors significantly predicted relapse-free survival. Conclusion: Myeloablative ASCT with TCD or unmodified allografts lead to comparable outcomes in this high-risk cohort of AML pts in CR1 with a lower acute GVHD rate observed after TCD transplants. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Approximately 80% of younger patients and 50% of older patients with newly diagnosed AML achieve CR after induction chemotherapy. The majority of patients who achieve CR eventually relapse, with most relapsing within the first 3 years. Long-term outcomes in pts maintaining 1st CR for at least 3 years (AML survivors) remain largely unknown. The purpose of this study was to investigate long-term outcomes in this subset of pts. Methods We performed a chart review of pts with AML treated at our institution who achieved CR for at least 3 years after their initial chemotherapy ± allogeneic stem cell transplant (ASCT) to analyze their long-term outcomes. Results 1792 pts with AML were treated between 2000 and 2010 at our institution. 1081 (60%) pts achieved CR. Among them, 266 (25%; 15% of all treated) maintained 1st CR for at least 3 years. The 1st 200 pts are described in this analysis: 33 after ASCT and 167 after chemotherapy (chemo) alone. Median time to CR from initiation of induction chemotherapy was 34 days (range, 19-115) for pts who received ASCT and 28 days (17-104) for chemo only. Characteristics of AML survivor pts at time of diagnosis were as follows: hypertension (HTN) was present in 25% of the pts; cardiac disease in 7%; hypothyroidism in 5%; diabetes (DM) in 7%; depression in 6%; osteoporosis in 2%; chronic obstructive disease (COPD) or asthma in 4%. Median number of medications per pt at baseline was 1 (0-7). Relapses after maintaining CR for ≥3 years (i.e., late relapses) were noted in 12% of the pts: 9% of the pts treated with ASCT and 12% of pts with chemo alone. The median CR duration for those who relapsed was 4 years (3-10) and 4.8 years (3-12), respectively. At relapse, karyotype was different from the karyotype at the time of diagnosis in 47% of the cases: 100% after ASCT and 41% after chemo alone. Mutational status changes at relapse were noted in 31% of the pts. New Flt3 ITD mutations were the most common change, noted in 75% of pts who had a mutational status change. A 2nd complete remission (CR2) was achieved in 52% of pts, including 33% of pts that had received ASCT and 56% of pts treated with chemo alone. The median CR2 duration was 5 months and 10 months (3-30) respectively. The median survival after relapse was 13 months (1 to 42). Four pts with relapsed disease who initially were treated with chemo only underwent ASCT; no patient received a 2nd ASCT. New medical problems that were present at the 3 year mark included: HTN in 10% of pts; cardiac disease in 4%; hypothyroidism in 4%; depression in 4%; renal insufficiency in 3%; pulmonary disease in 2%; DM in 3%; hematological disorders, including anemia, thrombocytopenia, monoclonal gammopathy of undetermined signigicance (MGUS), systemic mastocytosis & Waldenstorm’s macroglobulinemia, in 5%. Pulmonary disorders (e.g., bronchiolitis obliterans and COPD) occurred in 6% of pts who underwent ASCT and 2% of pts who treated with chemo alone. Renal insufficiency was noted in 9% of pts who underwent ASCT and in 2% of pts treated with chemo alone. The median number of medication per pt 3 yrs from initial CR was 3 (range, 0-11). New medical problems that developed at time of last follow up included: HTN in 12% of pts, cardiac disease in 6%, hypothyroidism in 5%, depression in 7%, renal insufficiency in 4%, pulmonary disease in 3%, DM in 5%, hematological disorders in 6%. Cardiac problems, including the development of coronary artery disease, myocardial infarction, congestive heart failure and arrhythmias were noted in 3% of pts who underwent ASCT and in 6% of pts treated with chemo alone. The median number of medications per pt at last follow up was 3 (0-14). Second malignancies occurred in 10% of pts. The most common 2nd malignancies were colorectal carcinoma, breast cancer, prostate cancer and lymphoma, each occurring in 2% of pts. At median follow up of 4.2 years (3.2-10.2) and 4.9 years (3.2-12) respectively, 94% and 80% of pts are alive. In descending order, the most common causes of death included AML relapse, second malignancy and myocardial infarction. Conclusion AML pts who achieved CR for at least 3 years have a low incidence of late relapses. New medical problems including heart disease and second malignancies may occur but most pts are still currently alive. AML pts who maintain 1st CR for at least 3 years require ongoing medical care and long-term surveillance. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3446 Background: The achievement of a fully chimeric state, as opposed to mixed chimerism, has been associated with a more favorable outcome after allogeneic stem cell transplantation (allo-SCT) for leukemia. When using the reduced-toxicity IV Busulfan-Fludarabine (Bu-Flu) regimen (de Lima et al, BLOOD 2004;104:857-64) we were intrigued by a seemingly high incidence of early (day+30) mixed chimerism, yet a low incidence of serious toxicity, GvHD and high overall and disease-free survival, especially for patients transplanted in (any) remission (CR). We hypothesized that the introduction of highly sensitive PCR-based chimerism assessment technique, as well as separately assaying myeloid- and T-cell chimerism might provide more reliable data for assessing the prognostic value of chimerism in reference to overall (OS) and disease-free survival (DFS) after allo-SCT. Patients and methods: Chimerism assay was performed with PCR-based technique on informative loci, and multi-variate Cox models including chimerism and other covariates were fit for OS and DFS (See Table 1). Results: 206 AML/MDS patients were treated on two consecutive protocols with Flu at 40 mg/m2 daily for 4 days, each dose followed by IV Bu at 130 mg/m2 or pharmacokinetically targeted to an average systemic exposure of 6,000 mcMol-min. Recipients of an unrelated or one-Ag mismatched related graft received rabbit-ATG at a total dose of 4 mg/kg on days -3 to -1. GvHD prophylaxis was Tacrolimus with mini-dose MTX (5 mg/m2) on post-transplant days 1, 3, 6, and 11. There were 98 females and 108 males at a median age of 47 years (range 16–66). Sixty-six patients were in CR1, 48 in CR2, 18 had 1st chemotherapy-refractory relapse, 20 were in 1st or 2nd untreated relapse, 37 had primary induction failure, while 17 had high-risk MDS. One patient died before day 30, without chimerism studies, and 11 recovered with refractory leukemia. Median follow-up of patients still alive is 5.5 yrs (range 1.3–8.6). 193 patients who engrafted and were in CR on day +30 had chimerism analysis performed, 64% were full donor chimeras, and 36% had mixed chimerism (≥1% remaining host cell-derived DNA). As expected, being in CR prior to SCT and, if transplanted with active disease, to engraft and remain in CR or to achieve CR, respectively, were important predictors for survival. A cytogenetic “bad” prognostic subgroup (e.g. -5/-7), was of adverse importance. However, in the multivariate model neither higher age, up to age 65, or attainment of full vs. mixed donor chimerism by day +30 were of additional predictive value for either OS or DFS. (See Table 1). Conclusion: When the reduced-toxicity IV Bu-Flu regimen is used as conditioning therapy for AML/MDS only cytogenetic subgroup (Bad/others) and disease state (CR/No CR) at the start of conditioning therapy influenced DFS and OS. Neither patient age nor attaining complete chimerism on BMT day +30 were independently predictive of an altered prognosis in reference to OS and DFS. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3537 Donor-recipient HLA mismatches are associated with increased morbidity and mortality after UD hematopoietic stem cell transplants (HSCT). We hypothesized that HLA-DP mismatches would worsen outcomes of HSCT using donors mismatched at HLA-A,-B,-C,-DRB1 or -DQB1 and evaluated 391 consecutive patients (pts) with myeloid malignancies treated at our institution with 0,1,2,3 mismatches out of 12 alleles typed by high resolution at HLA-A,-B,-C,-DR,-DQ,-DP loci. Eighty-one pts were 12/12, 180 pts were 11/12, 113 pts were 10/12, and 15 pts were 9/12 HLA match with the recipients. Characteristics of the 4 groups (12/12, 11/12, 10/12, 9/12) were similar except source of stem cells; 87% of pts with 9/12 donors received bone marrow versus 60–62% for the other 3 groups. Results: Two-year overall survival (OS) and progression-free survival (PFS) were 40%, 44%, 45%, 53% and 33%, 40%, 44%, 49%, respectively (p=NS). However, OS was significantly worse with increasing number of mismatches for patients with AML/MDS with poor-risk cytogenetics (p=0.005, HR 1.6, 95% CI 2.1–4.2). Except for the 9/12 group, pts had a significantly higher non-relapse mortality (NRM) (11%, 24%, 36%) and lower risk of progression (32%, 25%, 20%). In the 9/12 group, NRM was 27% and progression rate was 40%. Grade II-IV, III-IV aGVHD as well as cGVHD were also progressively worse with increasing number of mismatches. Gr II-IV and III-IV aGVHD rates were 35%, 37%, 41%, 69%, and 8%, 8%, 15%, 16%, respectively. Cumulative incidence of cGVHD was 35%, 39%, 44% and 61%, respectively. Compared with 11–12/12 donors, pts who received a 9–10/12 donor had significantly higher rates of gr III-IV aGVHD and cGVHD (p=0.03, HR 2.1, CI 1.1–3.7 and p=0.02, HR 1.5, CI 1.1–2.1, respectively). Univariate analysis revealed that there is less NRM with a 12/12 donor (vs. other) (p=0.008, HR 1.9, 95% CI 1.2–2.9), while in multivariate analysis, compared with a 12/12 donor, the use of a donor with mismatch was significantly associated with higher NRM [HR and 95%CI were 2.1 and 1.04–4.4 for 11/12 donor (p=0.04); 3.1 and 1.5–3.3 for 10/12 donor (p=0.003); 2.8 and 0.9–9.3 for a 9/12 donor (p=0.08), respectively] (Figure). In multivariate analysis, factors significantly associated with OS were disease status at transplant (active disease vs. not) (p

Description: Abstract 3445 Background: Relapsing AML/MDS after HSCT has a dismal prognosis, with few patients achieving long-term control of the malignancy. AZA is a hypomethylating agent that is moderately active against AML/MDS, and may have beneficial immunomodulatory effects after HSCT. We have shown that a significant minority of patients with recurrent disease respond to this drug. Here, we present long-term follow-up after salvage treatment regimens that included AZA, to treat AML/MDS that recurred after HSCT. Patients and Methods: Twenty-three patients received low-dose AZA for recurrence. Decision to use AZA was based on clinical assessment of slow progression of disease and relatively slower disease ‘tempo' and relatively small AML bulk. AZA cohort preparative regimens for 1st HSCT were myeloablative in 12 cases, and of reduced intensity in 11 cases. AZA was used prior to or without a 2nd HSCT (n=17), or after a 2nd HSCT (n=6). Outcomes were compared to controls (n=18) that relapsed ≥ 8 months after HSCT, and did not receive AZA (8 months representing the median disease free survival (DFS) for AZA-treated patients). The control group included all patients that relapsed ≥ 8 months after allogeneic HSCT using myeloablative busulfan 130 mg/m2 and fludarabine 40 mg/m2 for 4 days. AZA was studied as a time dependent variable. AZA and controls had similar baseline characteristics as described in the Table, although median DFS after the first HSCT was 8 (range: 2–51) and 17 (range: 7–59) months, favoring the control group (p=0.08). AZA was administered outpatient, with good tolerance. Fatigue and nausea were commonly observed toxicities. Doses were 8 mg/m2 (n=1), 16 mg/m2 (n=3), 24 mg/m2 (n=10), 32 mg/m2 (n=5), 40 mg/m2 (n=2), and 75 mg/m2 (n=2), administered subcutaneously for 5 days, in 28–32-day cycles. Results: Median number of cycles was 4 (range, 1–44). With a median follow-up of 18 months for AZA and control patients, median survival after relapse was 17 versus 6 months, respectively for AZA and control patients. 11 (48%) AZA patients are alive, while 2 (11%) control patients are alive. Two-year overall survival (OS) for AZA and control groups was 40% and 10%, respectively. AZA and controls had similar baseline characteristics as described in the Table. Conclusion: Low-dose AZA was a well tolerated outpatient treatment that may improve survival after AML/MDS recurrence in selected cases. Major determinants of survival in this setting, however, were remission duration after HSCT, and use of a 2nd HSCT. Disclosures: No relevant conflicts of interest to declare.