Decitabine As Induction Therapy For Median-To-High-Risk Myelodysplastic Syndromes(MDS) and Acute Myeloid Leukemia(AML) Before Allogeneic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentiallycurative therapy for patients with MDS and AML, especially with refractory and relapsed disease. The leading cause of the failure of Allo-HSCT lies in that critical organ disfunction and related complications are common in elderly patients .There’s no matched donor available and high relapse rate were additional risk factors for higher mortality of Allo-HSCT. Decitabine is the only demethylation drugs approved in China for treatment of median-to-high-risk MDS. Treatment with decitabine before Allo-HSCT could reduce tumor burden, keep the disease stable, and allow patients enough time to select a suitable donor.

46 patients with MDS (n=14)and AML (n=32)were admitted in hematological Dept. of First Affilated Hospital of Soochow University who all received treatment with decitabine alone or combined with chemotherapy followed by allo-HSCT between September 2009 andFebruary 2013. Disease classifications of 46 patients (median age 39ys, range 9-54ys) were as follows: RCMD (n=3), RAEB-1(n=2), RAEB-2 (n=9), refractory and relapsed acute leukemia (n=28) and MDS-AML (n=7). All MDS patients were median risk 2 according to IPSS. 57.1% MDS and 68.8% AML patients have chromosomal abnormalities. Patients were treated with decitabine 20mg/m2 for 3-5d alone (n=14) or plus CAG chemotherapy (n=32) prior to modified BuCY condition regimen. Acute graft-versus-host disease (GVHD) prevention regimen were cyclosporine-A (CsA) plus low-dose methotrexate (MTX) for allo-HSCT from HLA-identical sibling donor, anti-thymocyteglobulin (ATG), CsA,Mycophenolate mofetil(MMF) and low-dose MTX for HLA matched allo-HSCT from unrelated donor and HLA haplo-identical allo-HSCT from related donor. The overall response rate and complete remission rates of decitabine treatment before transplantation were 85.7%, 71.4% in MDS patients and 78.1%, 53.1% in AML patients respectively. 91.3% patients obtained successful engraftment. After a median follow-up of 8 months (2-33 months), the overall survival (OS) rate was 76.1%. Treatment-related mortality was 16.8% within 100 days. The incidences of acute and chronic GVHD among evaluable patients were 5.4% and 29.7%. Cumulative relapse rate was 39.1% after transplantation. The 33-months DFS rates and OS rates were 62.5% and 90% in patients who had achieved complete remission treated with decitabine induction prior to transplantation, while median DFS and OS were only 5 ms (p=0.008)and 12.4 ms(p=0.0004)in patients who had not. The survival advantage had nothing to do with the HLA typing and donor.

Decitabine induction is an effective therapy to bridge time to HSCT in MDS and AML patients with low treatment-related mortality. Its Improving therapeutic efficacy before transplantation will allow people obtain survival advantage post transplantation.