A Clinical Study Of Decitabine Combined With Standard Conditioning Regimen Prior To Allo-HSCT In The Treatment Of Relapse/refractory Acute Myeloid Leukemia

Part 1 A comparative study of outcomes of standard or decitabine intensified conditioning regimen prior to allo-HSCT in patients with relapse/refractory acute myeloid leukemiaObejective To evaluate the efficacy of decitabine(DAC)intensified conditioning regimen prior to allogeneic hematopoietic stem cell transplantation(allo-HSCT)in the treatment of relapse/refractory acute myeloid leukemia(AML),reduce the recurrence and improve the poor prognosis of relapse/refractory AML.Methods The clinical characteristics and therapeutic effects of 65 patients with relapse /refractory AML receiving allo-HSCT from April 2006 to May 2016 were retrospectively analyzed.Contents 27 patients receiving standard conditioning regimen were selected as control group,20 patients receiving high-dose DAC intensified conditioning regimen and 18 patients receiving low-dose DAC intensified conditioning regimen were selected(referred as to the high-dose DAC group and the low-dose DAC group separately).we primarily analyzed the neutrophil and platelet engraftment,transplant-related mortality(TRM),occurrence of graft versus host disease(GVHD)and survival status of patients.Results Patients engrafted to an neutrophil exceeding 0.5×109/L,with a median time of 16 days(range,12–29 days)in the standard group,15 days(range,10–18 days)in the high-dose DAC group and 16 days(range,11–22 days)in the low-dose DAC group,respectively(P=0.306>0.05).All patients engrafted to an platelet exceeding 20×109/L,with a median time of 19 days(range,14–38 days)in the standard group,17.5 days(range,13–36 days)in the high-dose DAC group and 16.5 days(range,14–35 days)in the low-dose DAC group,respectively(P=0.286>0.05).1 of 27 patients receiving standard conditioning regimen died of cardiac sudden death.The cumulative incidences of TRM at 1 year were 4.2% in the standard DAC regimen group.4 of 20 patients receiving high-dose DAC intensified conditioning regimen died of the complication of transplantation,3 patients died of severe infection and 1 patient died of cardiac sudden death.The cumulative incidences of TRM at 1 year were 25.2% in the high-dose DAC regimen group.5 of 18 patients receiving low-dose DAC intensified conditioning regimen died of the complication of transplantation.3 patients died of severe infection,1 patient died of severe a GVHD and 1 patient die of engraftment failure.The cumulative incidences of TRM at 1 year were 30.2% in the low-dose DAC regimen group.of 17 patients in the standard group with a GVHD,14 were grade Ⅱ-Ⅳ a GVHD and 6 were grade Ⅲ-Ⅳ a GVHD.Of 8 patients in the high-dose DAC group with a GVHD,2 were grade Ⅱ-Ⅳ a GVHD,none of patients in this group had grade Ⅲ-Ⅳ a GVHD.Of 10 patients in the low-dose DAC regimen group with a GVHD,7 were grade Ⅱ-Ⅳ a GVHD and 2 were grade Ⅲ-Ⅳ a GVHD.The gradeⅡ-Ⅳ a GVHD incidence of patients in the standard group(52.8%)wassignificantly higher than patients in the high-dose DAC group(10%),there was remarkable difference in statistics between the two groups(p=0.029<0.05).In the low-dose DAC regimen group,2 patients had grade Ⅲ-Ⅳ acute GVHD,a combination of methelprednisolone(1 to 2 mg/kg/d)and Secondline immunosuppressive therapy was treated to them,but the patients had no response to these treatments.In the end,one patients died of severe bloody diarrhea and one died of severe pneumonia.4 of 23 patients in the standard regimen had grade Ⅲ-Ⅳ acute GVHD,all of them had survived for good response to treatments.The 1-year OS probabilities were 22.2%,68.8% and 27.8% for patients inthe control group,high-dose DAC group and low-dose DAC group,respectively(p=0.007<0.05).The 1-year probabilities of LFS were 22.2%,58.5% and 20.8% after transplantation conditioned with standard regimen,high-dose regimen and low-dose regimen,respectively(p=0.023<0.05).Conclusions 1.High-dose DAC combined with standard conditioning regimen may lowerthe incidences of grade Ⅱ-Ⅳ aGVHD.2.High-dose DAC combined with standard conditioning regimen can improve the outcome on LFS and OS of patients with relapse/refractory AML.Part 2 Clinical study of decitabine intensified conditioning regimen and idarubicin intensified conditioning regimen prior to hematopoietic stem cell transplantation in the treatment of refractory/relapse acute myeloid leukemia.Objective To observe the treatment results of 44 consecutive patients with relapse/refractory acute myeloid leukemia(AML)not in remission who received allo-HSCT,following decitabine(DAC)-intensified conditioning regimen(18)and idarubicin(IDA)-intensified conditioning regimen(26).Methods We conducted a retrospective study to evaluate the outcome of 44 consecutive patients with relapse/refractory acute myeloid leukemia(AML)not in remission who received allo-HSCT from 2009 July to 2016 May.Contents 18 patients received high-dose decitabine-intensified conditioning regimen and 26 patients received idarubicin-intensified conditioning regimen prior to allo-HSCT.The effects of decitabine and idarubicin intensified conditioning regimen on the patients’ engraftment,tansplant-related mortality,survival and occurrence of graft versus host disease(GVHD)were analyzed.Results All patients achieved neutrophil and platelet engraftment.Patients engrafted to an neutrophil exceeding 0.5×109/L,with a median time of 15 days(range,10–18 days)in the DAC group and 14 days(range,12–22 days)in the IDA group,respectively(P=0.125>0.05).All patients engrafted to an platelet exceeding 20×109/L,with a median time of 19 days(range,14–35 days)in the IDA group,18 days(range,13–36 days)in the DAC group,respectively(P=0.503>0.05).In the DAC group,3 patients died of severe infection and 1 patient died of cardiac sudden death.2 of 26 patients receiving IDA intensified conditioning regimen died of severe infection.In the DAC group,7(38.9%)patients had acute graft versus host disease(GVHD.Among them,2 patients had gradeⅠacute graft versus host disease(GVHD),5 patients had gradeⅡacute graft versus host disease(GVHD).In the idarubicin(IDA)group,16(61.5%)patients had acute graft versus host disease(GVHD).Among them,9 patients had gradeⅠacute graft versus host disease(GVHD),6 patients had gradeⅡacute graftversus host disease(GVHD)and 1 patient had grade Ⅲ acute graft versus host disease(GVHD).In the idarubicin(IDA)group,9 of 26(34.6%)patients experienced leukemia relapse,all of them died due to the lack of effective therapies.In the decitabine(DAC)group,4 of 18(22.2%)patients experienced leukemia relapse,2 of them got long-term survival throughout salvage therapies.For the decitabine(DAC)group and idarubicin(IDA)group,the 1-year probabilities of overall survival(OS)and leukemia-free survival(LFS)were 65.0% versus 57.7%(p=0.602)and 53.5% versus 57.7%(p=0.910),respectively.Conclusions 1.Decitabine-intensified conditioning regimen before allo-HSCT in the treatment of AML is safe and effective.2.The incidence of a GVHD in the DAC group was lower than IDA group,but there was no statistically significant difference due to the small sample and retrospective nature of this study.3.Decitabine-intensified conditioning regimen can achieve a clinical efficacy which is no less than IDA-intensified conditioning regimen without increasing the pretreatment toxicity.