Multicenter Study Evaluating the Impact of Hypomethylating Agents As Bridging Therapy to Hematopoietic Stem Cell Transplantation in Myelodysplastic Syndromes

Abstract

AbstractAbstract ▪3806▪This icon denotes a clinically relevant abstract Introduction:Allogeneic hematopoietic stem cell transplantation (alloHCT) is the only curative modality for myelodysplastic syndromes (MDS). Recently, treatment paradigm has changed since the introduction of hypomethylating agent (HMA) to treatment of MDS. There is little known about effect of HMA to transplant outcome and appropriate dose and schedule when used as bridging therapy to alloHCT. Therefore this retrospective multicenter study aimed to assess the effect of pre-transplant HMA on transplant outcome and aimed to determinate the patient who would benefit from pre-transplant HMA therapy. Method:Medical record of 113 patients (male n=69; female n=44) were reviewed. Patients who received alloHCT from 2007 to 2010 were enrolled regardless of pre-transplant HMA therapy. Five institutions participated. Primary endpoint event-free survival (EFS) after alloHCT. Second endpoint was engraftment after alloHCT. Analysis was done by HMA versus non-HMA. Results:Eighty-five of the 113 patients were treated with HMA before HSCT (51 with Azacitidine (AZA), 30 with Decitabine (DCT) and 4 with both alternatively). Twenty-eight patients received alloHCT without HMA bridging. The median age 47 (range 20–69) for HMA group and 42 (range 17–64) for non-HMA group (P=0.035). Distribution of WHO classification group and IPSS score were similar criteria (P=0.230 and P=0.328), For HMA group, median number of HMA administration was 5 cycles (range 1∼20). Among HMA treated patients, 21 (18.5 %) achieved complete response (CR) or marrow CR (mCR) and 4 (3.5 %) achieved partial response (PR). For all patients, median EFS was 29 ± 2 months. IPSS score at diagnosis(Low/Intermediate (INT)-1 vs. INT-2/High) affected overall survival (OS) after alloHCT (32 ± 3 vs. 25 ± 4 months, respectively; P=0.020). Pre-transplant HMA didn’t affect OS (P=0.771) and there was also no difference between AZA and DCT (P=0.60). However, for patient with high blast count (>5% of bone marrow at diagnosis) pre-transplant HMA therapy had a benefit of 1-yr EFS (16.7 % for non-HMA vs. 67.9 % for HMA, P=0.126) Median time to neutrophil engraftment was 28 (range, 2∼380 days) for HMA and 12 (range, 7∼18 days) for non-HMA (P=0.031). Median time for platelet engraftment was 35 for HMA group and 19 for non-HMA group (P=0.052). Effect of HMA to graft-versus-host disease or graft failure was uncertain. Conclusion:Benefit of bridging therapy of HMA before alloHCT was not definite by this retrospective study. However for a proportion of patients with high leukemic burden, HMA tended to have benefit for post-HCT EFS. There was considerable delay of engraftment among HMA treated patients. Therefore, pre-HCT bridging HMA therapy may not be appropriate for all MDS patients. Prospective trial is required to confirm the benefit and effect of HMA bridging therapy to alloHCT. Disclosures:No relevant conflicts of interest to declare.