| Juvenile myelomonocytic leukemia(JMML)is usually poor respond to chemotherapy,and approximately 30-35%of patients relapse after hematopoietic stem cell transplantation(HSCT).Recent studies have highlighted the importance of epigenetic aberrations in JMML and proved that some JMML stem cells were associated with hypermethylation.Hence,we designed the current study to investigate whether low dose Decitabine could improve outcomes of JMML-HSCT.Patients and method:22 patients received HSCT combined with Decitabine between December 2014 and December 2017.The median age at diagnosis was 29.5months(range:1-71 months).21/22 patients received 2-4 course mild chemotherapy(one patient,case 6,received only single course Decitabine therapy)before HSCT.3 patients received HSCT from HLA matched unrelated donors(MUD),and 19 patients received the complementary transplantation,unrelated cord blood(UCB)was given at 6 days after haploidentical peripheral blood stem cell transplantation(PBSCT)using high dose cyclophosphamide(Cy)post-transplant(PTCy).Conditioning regimen composed of Cy,Busulfan(Bu)/Thiotepa(TT),fludarabine(Flu),and ATG-F in the MUD-HSCT,and Cy,Bu,Flu and Cytarabine(AraC)in the CT.Patients received a fixed dose of 8×10^8/kg mononuclear cells(MNC)in the MUD-HSCT,and a median dose of 47.2×10^8/kg(range,22.77-88×10^8/kg)mobilized peripheral blood MNCs and a median dose of 8.68×10^7/kg(range,3.99?12.75×10^7/kg)UCB nucleated cells in the CT,respectively.Graft-versus-host disease(GVHD)prophylaxis were consist of PTCy,mycophenolate mofetil(MMF)and tacrolimus(Tac)in the CT,and ATG,CsA and MMF in the MUD-HSCT.Decitabine was administrated for 2-3 courses(20mg/m2.d×5 day for each course with 4?6-week interval)before HSCT to reduce load of leukemia cells and for 2?6 courses(10±5mg/m2.dayx5day for each course with the interval of 4?8 weeks)after HSCT to overcome immune-escape of leukemia cells.The drug dosages were adjusted according to the extent of bone marrow suppression.Before HSCT,3 cases got clinical complete remission(cCR),1 case got clinical genetic complete remission(gCR),the other got 18 cases(PR),and no one progress before HSCT.Results:The median follow-up time was 8.5 months(range,2-45 months).Full donor cells engrafted in all patients(donor cell engraftment in case 6 occurred in a salvaged transplant from another haplo-donor after primary failure of first CT).Overall survival and disease-free survival were 95.5%and 86.4%respectively.In the CT,haplo-cells and UCB-cells engrafted finally in 10 and 9 patients,respectively.The median times to neutrophil engraftment(defined as the first of 3 days of an absolute neutrophil count>0.5×10^9/L)and platelet engraftment(defined as a platelet count?20 × 10^9/L without transfusion for the preceding 7 days)were 30 days(range,18?71 day)and 17 days(range,12?35 day),and 23.5 days(range,9?105 day)and 12 days(range,10?30 day)post-transplant,respectively in the CT group and MUD group,case 12 and case 18 both developed relapse about 3 months after HSCT,and have been undergoing the second salvaged transplantation till the end of follow time of this research.The cumulative incidences of grades ?-? aGVHD was 31.8%(7/22).Case 6 had grade ? aGVHD.Case 13 died from gut grade ?°aGVHD at +50 days after the CT.Chronic GVHD occurred in 3 patients,and no chronic GVHD more than grade ?(NIH criterion)occurred in all patients.The most common complication associated HSCT was fever of undetermined origin(FUO).The incidences of CMV and EBV antigenmia were 27.2%(6/22)and 4.5%(1/22),respectively.Six patients developed recoverable serious pancytopenia,one patient developed neutropenia,and one patient developed thrombocytopenia during the post-HSCT Decitabine therapy.Discussion:The combination of hypomethylation agent with HSCT showed encouraging results in JMML-HSCT.It is impressed that only one of 22 pts occurred relapse despite short follow-up time.A large-cohort study with extending follow-up time should be developed in the future. |
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