Significance Of Minimal Residual Disease Detected By Flow Cytometry In Patients With Acute Leukemia Undergoing Allogeneic Nonmyeloablative Hematopoietic Stem Cell Transplantation

Objective:To study the relationship between minimal residual disease(MRD)by flow cytometry(FCM)and the relapse of acute leukemia(AL)in adult patients after allogeneic nonmyeloablative hematopoietic stem cell transplantation(NST).Furthermore,to determine an appropriate cutoff value of minimal residual disease by flow cytometry(FCMRD)for the purpose of early prediction of post-NST relapse.In addition,to evaluate the efficacy of donor peripheral blood stem cells infusion(DSI)and immunosuppression withdrawal to prevent leukemia relapse.Methods:Patients needed to be in complete remission(CR),older than 14 years and have available FCMRD within 35 days before NST.From January 2011 and December 2015,a total of 51 patients met these criteria and were included in this retrospective study.We use ROC curve analysis for FCMRD and AL recurrence to determine an appropriate cutoff of FCMRD.High-level FCMRD group was defined as FCMRD?0.2% post-NST at least for one time while low-level MRD group was defined as FCMRD<0.2% post-NST all the times.Two-year cumulative incidences of relapse of the two groups were compared.In study,we explored possible risk factors of AL relapse.The patients whose FCMRD ? the selected cutoff value were divided into two groups.In one group,all patients received DSI with immunosuppression withdrawal;In another group,all patients had immunosuppression withdrawal without DSI.The recurrence rates were compared between the two groups.Results: The two years cumulative recurrence rate(CIR)after the NST was 21.56%.The mortality rate were 81.8% and 46.3%(P=0.036)in relapse group and non-relapse group respectively.The area under the ROC curve for pre-NST FCMRD and recurrence was 0.53(P=0.783).The area under the ROC curve for post-NST FCMRD and recurrence was 0.864(P<0.001).The appropriate cutoff value of post-FCMRM was 0.02% with the sensitivity of 81.8% and the specificity of 77.5% for prediction of recurrence.Two-year relapse rates were 6.1% and 50% in low-level FCMRD group and high-level FCMRD group post-NST(P=0.001)respectively.Multivariate analysis indicated the risk of relapse was 5.84 times(P=0.036)higher in high-level FCMRD group.FCMRD?0.2% post-NST was an independent risk factor for leukemia relapse.In high-level FCMRD group,1 out of 4 patients with DSI and immunosuppression withdrawal relapsed and 5 out of 9 patients with immunosuppression withdrawal but without DSI relapsed.Conclusions: 1.Dynamic monitoring of MRD by FCM was a crucial tool for early relapse estimation of acute leukemia in adult patients after NST.The MRD by flow cytometry after NST was significantly associated with the AL relapse.2.The relapse patients after transplantation was difficult for treatment and had high mortality.3.FCMRD?0.2% post-NST with high sensitivity and specificity could be a early valuable predictor of relapse and indicate active medical intervention needed.