Clinical Study Of Allo-HSCT With Conditioning Regimen Containing Decitabine In The Treatment Of Advanced Malignant Hematologic Disease

Objective:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curativetreatment options to hematologic malignancies. However, majority of patients withrefractory or resistant hematologic malignancies can not achieve remission beforetransplantation. And the relapse rate of these patients after transplantation remains highobviously. Therefore, it is necessary to design a safe and effective conditioning regimen toimprove the remission rate of these patients and disease-free survival (DFS), but to reducetransplantation related mortality (TRM).The optimal conditioning regimen not only canreduce tumor burden and eradicate minimal residual disease but also can makeimmunosuppressive state to ensure engraftment. As well as, it does not increase the TRM.One of the promising drugs of epigenetics is decitabine(DAC), which has a significanteffect on a variety of hematologic malignancies. It is widely used in myelodysplasticsyndromes(MDS) even for relapsed and refractory acute myelocytic leukaemia (AML).Because decitabine can not only up-modulate the tumor-associated antigen express onsurface of leukemia cells to increase graft-versus-leukemia (GVL) effect but also canreduce the incidence of graft-versus-host disease (GVHD) by increase the number ofregulatory T Cells（Tregs）.This clinical study will investigate the security and efficacy ofconditioning regimen containing decitabine. Further to explore the role in advancedmalignant hematologic disease.Methods21cases of patients with hematologic malignancies underwent allo-HSCT with decitabinecombined with conditioning regimens in the Department of Hematology, the FirstAffiliated Hospital of Soochow University during May1,2012to February28,2014.There are15males and6females, median age41years (9-55years old);17cases of acutemyeloid leukemia(AML)(11cases of refractory or relapsed AML)；3cases ofmyelodysplastic syndrome (MDS)；and one case of hybied acute leukemial(HAL). Amongthem, there are10cases (47.6%) with complex chromosomal karyotype or chromosome7abnormalities or with DNMT3A mutation. The objective of our study was to evaluatetoxicity of this regimen, hematopoietic reconstitution, door chimerism (STR), transplantrelated complications, relapse rate and overall survival.Results：20patients achieved complete remission and hematopoietic reconstitution aftertransplantation. Only1case relapsed on day+20and died on day+27post transplant. Themedian time of neutrophil and platelet reconstitution were12(10-22) and14.5(12-35)days respectively. The median time of archiving full donor chimerism （STR>95%）was18(13-62) days. The median follow-up post transplant was212(27-577) days.5casesrelapsed.4cases were dead due to relapse.1case achieved complete remission again afterdonor lymphocyte infusion (DLI).1CR case was dead due to hemorrhage of digestivetract.1CR case was suicide due to depression. The other14CR cases were survival withcontinued remission.The estimated2-year overall survival (2yr-OS) rate was63.3%.The2year disease-free survival (2yr-DFS) rate was55.3%. The cumulative relapse rate was38.7%.The non-relapse mortality rate was9.5%and transplantation-related mortality(TRM) rate was only4.8%. Furthermore, the estimated2-yr OS and DFS of patients withDNMT3A mutations or abnormalities of chromosome7and complex chromosomalkaryotype were56.3%and57.1%respectively. Concerning about transplant related toxicity,except one case has grade III gastrointestinal toxicity, all the other toxicities were mild(grade I-II). The cumulative rate of aGVHD and cGVHD were28.6%and44.5%.And thecumulative rate of aGVHD for grade I-II、grade IIIand grade IV were14.3%、9.5%and4.8%。Conclusion1. Allo-HSCT is an effective treatment for refractory and relapsed AML and high-riskMDS. It is feasible to use conditioning regimen containing decitabine beforeallo-HSCT.The treatment were well tolerated. The transplant related mortality rate wasonly4.8%,and the non relapse mortality rate was just9.5%.2.95.2%of the patiants achieved CR,and were well engraftment. Because of decitabine can promote megakaryocytic maturation and accelerate the release of platelet, sohematopoietic was reconstructed rapidly, especially for the megakaryocyte. The2yr-DFS rate was55.3%, the cumulative relapse rate was38.7%. The conditioningregimen containing decitabine before allo-HSCT seems to reduce the incidence ofaGVHD.3. The prognosis and survival of the patients with complex chromosomal karyotype orchromosome7abnormalities or DNMT3A mutation may be improved by treating withdecitabine containing conditioning regimen.