Comparison Between Upfront Transplantation And Cytoreductive Therapy Pre-transplantation In Patients With MDS-EB-1 Or MDS-EB-2

Background:It is controversial whether cytoreductive therapy before allogeneic hematopoietic stem cell transplantation(allo-HSCT)is associated with the superior outcomes thanupfront transplantation.This debate mainly depend on patients who ultimately received transplantation.This study was to compare the efficacy of upfront transplantation and cytoreductive therapy pre-transplantation not only in patients who ultimately received transplantation but also who drop out transplantation because of cytoreductive therapy related adverse events.METHODS:A total of 151 patients with MDS-EB-1 or MDS-EB-2 who received treatment between January 2010 and December 2016 were enrolled in this study.Depending on whether they received cytoreductive therapy before transplantation,patients were divided into 3 groups:upfront transplantation(Upfront group;n=53);induction chemotherapy before transplantation(ICT group;n=64),hypomethylating agents(HMA group;n=34).RESULTS:Of the 151 enrolled patients,118 patients ultimately received allo-HSCT,with 5.6%,29.7%and 32.4%of drop-out rate of transplantation in Upfront,ICT and HMA groups,respectively(P=0.03).The 2-year cumulative incidence of relapse post-transplantation were 12.0%,22.2%and 20.7%respectively(P=0.038),with lower in Upfront than ICT and HMA groups(P=0.032 P=0.041 respectively).The 5-year overall TRM were 13.0%,32.4%and 28.4%,respectively(P=0.028),with lower in Upfront than ICT and HMA groups(P=0.012,P=0.037,respectively).The 5-year OS post-diagnosis was 73.6%(95%confidence interval,70.3-76.9),43.4%(39.2-47.6)and 46.9%(44.7-49.1),respectively in Upfront,ICT and HMA groups(P=0.033).OS in Upfront was longer than ICT and HMA(P=0.045 and P=0.002,respectively),while similar between ICT and HMA(P=0.61).The 5-year TRM post-transplantation were 14.5%(12.4-16.1),20.0%(18.1-23.2)and 17.6%(16.2-18.2)in Upfront,ICT and HMA,respectively,while similar among 3 groups(P=0.651).The 5-year OS post-transplantation was 77.3%(72.5-82.1),64.3%(59.0-69.6)and 68.8%(61.9-76.0)in Upfront,ICT and HMA,respectively(P=0.047).It was superior in Upfront than in ICT(P=0.048)while it was similar when comparing Upfront and HMA or comparing HMA and ICT(P=0.066 and P=0.672,respectively).The 5-year DFS was 74.0%(68.2-79.8),63.0%(59.4-66.6)and 65.8%(60.5-71.1)in Upfront,ICT and HMA groups,respectively(P=0.042),it was superior in Upfront than in ICT(P=0.044)while similar when comparing Upfront and HMA or comparing HMA and ICT(P=0.27 and P=0.073,respectively).CONCLUSIONS:Cytoreductive therapy pre-transplantation can’t improve survival because adverse events of cytoreductive therapy lead some patients to drop out transplantation and increase relapse.Upfront transplantation should be preferable for patients with MDS-EB-1 or MDS-EB-2.