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The European Society for Blood and Marrow Transplant Research data set was used to retrospectively analyze the outcomes of hypomethylating therapy (HMA) compared with those of conventional chemotherapy (CC) before hematopoietic stem cell transplantation (HSCT) in 209 patients with advanced myelodysplastic syndromes. Median follow-up was 22.1 months and the median age of the group was 57.6 years with 37% of the population older than > 60 years. The majority of patients (59%) received reduced-intensity conditioning and 34% and 27% had intermediate-2 and high international prognostic scoring system (IPSS) scores. At time of HSCT, 32% of patients did not achieve complete remission (CR) and 13% had primary refractory disease. On univariate analysis, outcomes at 3 years were not significantly different between HMA and CC for overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM): OS (42% versus 35%), RFS (29% versus 31%), CIR (45% versus 40%), and NRM (26% versus 28%). Comparing characteristics of the groups, there were more patients < 55 years old, more patients in CR (68% versus 32%), and fewer patients with primary refractory disease in the CC group than in the HMA group (10% versus 19%, P < .001). Patients with primary refractory disease had worse outcomes than those in CR with regard to OS (hazard ratio [HR], 2.42; 95% confidence interval [CI], 1.41 to 4.13; P = .001), RFS (HR, 2.27; 95% CI, 1.37 to 3.76; P = .001), and NRM (HR, 2.49; 95% CI, 1.18 to 5.26; P = .016). In addition, an adverse effect of IPSS-R cytogenetic risk group was evident for RFS. In summary, outcomes after HSCT are similar for patients receiving HMA compared with those receiving CC, despite the higher proportion of patients with primary refractory disease in the HMA group., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a potential cure for patients with myelodysplastic syndrome (MDS) who are ineligible for standard-intensity regimens. Previously published data from our institution suggest excellent outcomes at 1 yr using a uniform fludarabine, busulfan, and alemtuzumab-based regimen. Here we report long-term follow-up of 192 patients with MDS and acute myelogenous leukemia (AML) secondary to MDS (MDS-AML) transplanted with this protocol, using sibling (n = 45) or matched unrelated (n = 147) donors. The median age of the cohort was 57 yr (range, 21 to 72 yr), and median follow-up was 4.5 yr (range, 0.1 to 10.6 yr). The 5-yr overall survival (OS), event-free survival, and nonrelapse mortality were 44%, 33%, and 26% respectively. The incidence of de novo chronic graft-versus-host disease (GVHD) was low at 19%, illustrating the efficacy of alemtuzumab for GVHD prophylaxis. Conversely, the 5-yr relapse rate was 51%. For younger patients (age <50 yr), the 5-yr OS and relapse rates were 58% and 39%, respectively. On multivariate analysis, advanced age predicted significantly worse outcomes, with patients age >60 yr having a 5-yr OS of 15% and relapse rate of 66%. Patients receiving preemptive donor lymphocyte infusions had an impressive 5-yr OS of 67%, suggesting that this protocol may lend itself to the incorporation of immunotherapeutic strategies. Overall, these data demonstrate good 5-yr OS for patients with MDS and MDS-AML undergoing alemtuzumab-based RIC-HSCT. The low rate of chronic GVHD is encouraging, and comparative studies with other RIC protocols are warranted., (Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.)

Relapse occurs in 30%-50% of recipients of T cell-depleted (TCD) reduced-intensity conditioned (RIC) hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Despite limited published supportive data, donor lymphocyte infusion (DLI) is used preemptively (pDLI) to improve donor chimerism and prevent relapse, and therapeutically (tDLI) after disease recurrence. We evaluated the efficacy and toxicity of pDLI and tDLI in 113 patients after TCD (alemtuzumab, n = 99; antithymocyte globulin, n = 14) RIC HSCT for AML or MDS. Recipients of pDLI (n = 62) had an estimated 5-year overall survival (OS) of 80% and an event-free survival of 65%. More than one-half (52%; n = 32) of the patients received pDLI within 6 months post-HSCT; despite this, the 5-year incidence of graft-versus-host disease was only 31% (95% confidence interval [CI], 19%-43%). Recipients of tDLI (n = 51) had an estimated 5-year OS of 40% and a 5-year relapse/progression rate of 69% (95% CI, 54%-81%). Recipients of tDLI at >6 months post-HSCT had a significantly superior 5-year OS after tDLI compared with those treated earlier (P = .008). The cumulative incidence of graft-versus-host disease at 5 years after tDLI was 45% (95% CI, 23%-65%). We demonstrate that pDLI safely promotes durable remission after TCD RIC HSCT for AML or MDS, and that tDLI salvages patients after late relapse with greater efficacy., (Copyright © 2013. Published by Elsevier Inc.)