| Background and purposeAcute myeloid leukemia(AML)is a malignancy originating from myeloid progenitor cells with biologically complexity and molecularly and clinically heterogeneity,40-60%of patients diagnose with cytogenetics and molecular abnormalities.The median age was older than 65 years.About 70%of AML patients achieve complete remission(CR)after one or two course of induction therapy,while about one third of the patients failed to reached CR after two courses of induction.In addition,more than half of the CR patients will eventually relapsed and the prognosis remains very poor.After CR,appropriate post remission therapy(PRT)is essential to prevent relapse.PRT usually includes high-dose cytarabine based consolidation chemotherapy,autologous hematopoietic stem cell transplantation(auto-HSCT)and allogeneic hematopoietic stem cell transplantation(allo-HSCT).Allo-HSCT is the most effective method to prevent relapse.For relapsed/refractory AML patients,allo-HSCT is also the only curative option.HLA matched sibling donors(MSD)was the optimum donor source for allo-HSCT.However,70%of patients cannot obtain a suitable MSD.Increasing researches have shown that the effectiveness of HLA-haploidentical donor(HID)HSCT is comparable to that of MSD transplantation.HID transplantation is a safe and effective treatment option for patients with hematologic malignancies who lack an MSD.However,it is still remaining controversial whether HID transplantation has the same effectiveness as MSD transplantation for CR AML.Some transplantation centers reported that the effect of two donor types of transplantation was similar on CR AML patients,while others considered that MSD transplantation was better than of HID as PRT choice for CR AML.At present,there are also controversial about whether HID transplantation has the same effect in relapsed/refractory AML.Different transplantation centers report the different conclusions.How et al.reported that there were no significant differences in the efficacy between HID,unrelated donor transplantation and MSD transplantation in the treatment of relapsed/refractory AML.The study of the First Affiliated Hospital of Soochow University reported similar results.In a large-scale retrospective study of EBMT data,Battipaglia et al.Compared the results of HID and MSD transplantation in the treatment of relapsed/refractory AML,and found that the overall survival,disease-free survival of HID group was significantly lower than those of MSD group.The authors therefore suggested that MSD is still the gold standard for allo-HSCT of relapsed/refractory AML.Because of more complications and higher transplantation related mortality,elderly AML patients usually do not consider allo-HSCT.With the progress of conditioning,GVHD prophylaxis and support care,the upper age of patients undergoing allo-HSCT has gradually increased from 40-45 years old to over 75 years old now.More and more reports have shown that allo-HSCT can improve the prognosis of elderly AML patients.Compared with young patients,elderly patients have less chance to obtain suitable MSD because-their siblings are often elderly,and their physical fitness may not be suitable for allo-HSCT donors.Studies of HID transplantation in the elderly is relatively limited.Studies of whether HID transplantation can be safe and effective in the treatment of elderly AML is also relatively limited.In order to compare the effectiveness of HID and MSD transplantation in the treatment of OR AML patients,in relapsed/refractory AML patients and in AML patients older than 50 years,we analyzed the data of AML patients received MSD or HID transplantation in our institution from January 2012 to December 2018 and compared the hematopoietic reconstitution,infection,graft-versus-host disease,relapse,non-relapse mortality,disease-free survival and overall survival of the two donor types of transplantation.The purpose of this study is to guide the PRT selection of AML patients,the donor selection of relapsed/refractory AML and the donor selection of elderly AML patients.MethodWe retrospectively analyzed the data of adult AML patients underwent MSD or HID transplantation in our center from January 2012 to December 2018.Four hundred and thirty-five CR AML patients were included in the part one,including 204 MSD transplantation and 231 HID transplantation.In the second part,63 patients with relapsed/refractory AML were included,including 27 sibling MSD transplantation and 36 HID transplantation.In the third part,92 patients with AML age>50 years old were included,including 49 MSD transplantation and 43 HID transplantation.The clinical data including patient’age,gender,diagnosis,disease status at HSCT,condition,donor(MSD or HID)and other clinical features and complications.All patients received myeloablative regimen.Cyclosporine A(CsA)or CsA plus methotrexate(MTX)was used for MSD patients,and CsA plus MTX plus antithymocyte globulin(ATG)plus mycophenolate mofetil(MMF)were used for HID patients for GVHD prophylaxis.In HID group,the grafts were G-CSF mobilized bone marrow plus peripheral blood,while in MSD group the grafts were G-CSF mobilized peripheral blood stem cells.The hematopoietic reconstitution,GVHD,relapse,non-relapse mortality(NRM),relapse free survival(RFS)and overall survival(OS)were compared between the two donor types.The efficacy of HID and MSD transplantation in the treatment of CR AML,in relapsed/refractory AML and in elderly AML patients older than 50 years were analyzed.All statistical analysis was performed by SPSS 24 software.Results1.In the first part of 435 CR AML patients,the cumulative incidence(CI)of Ⅱ-Ⅳ° acute GVHD at 100 days was 42.0 ±3.2%vs 22.1 ± 2.9%(P=0.000),and the Cl of Ⅲ-Ⅳ° acute GVHD was 11.3 ±2.1%vs 10.2 ± 2.3%(P=0.773),respectively for HID and MSD groups.The Cl of chronic GVHD at two years was 44.1 ± 3.5%vs 38.7 ± 3.6%(P=0.167),and the CI of extensive chronic GVHD was 14.8 ± 2.5%vs 17.3 ± 2.8%(P=0.671),respectively for HID and MSD groups.The CI of CMV infection at one year was 66.8 ± 3.1%vs 35.3±3.3%(P=0·000),and the CI of EBV infection at one year was 41.1 ± 3.2%vs 14.2±2.4%(P=0.000),respectively for HID and MSD groups.Of the 435 patients,103 patients relapsed after HSCT,and the relapse rate at 3-years were 20.8 ± 2.8%vs 28.3 ±3.4%(P=0.217)for HID and MSD groups.Forty-six patients died of non-relapse mortalities(NRM),and the NRM rate at 3-year were 13.1 ± 2.3%vs 8.6 ± 2.1%(P=0.147)for HID and MSD groups.The 3-year overall survival(OS)was 70.2 ± 3.0%vs 69.7 ± 3.2%(P=0.962),and the 3-year relapse free survival(RFS)was 67.2 ± 3.1%vs 66.4 ± 3.4%(P=0.744),respectively for HID and MSD groups.In the subgroup analysis,the CI of relapse rate at 3-year,3-year OS and 3-year RFS were 13.4 ± 7.2%vs 17.9 ± 7.4%(P=0.714);72.6 ± 8.8%vs 80.0 ± 7.3%(P=0.571)and 69.2 ± 9.1%vs 76.7 ± 7.7%(P=0.500),respectively for HID and MSD groups in the favorable risk patients.The 3-year CI of relapse,OS and RFS were 20.3 ± 4.8%vs 22.3±5.1%(P=0.941),73.5± 5.1%vs 74.8 ± 5.1%(P=0.708)and 69.6 ± 5.3%vs 71.6± 5.4%(P=0.580),respectively for HID and MSD groups in the intermediate risk patients.The 3-year CI of relapse,OS and RFS were 22.5±3.9%vs 36.8 ± 5.2%(P=0.074),67.8± 4.2%vs 63.1 ± 4.8%(P=0.478)and 65.4± 4.2%vs 59.8 ± 5.0%(P=0.673),respectively for HID and MSD groups in the poor risk patients.2.In the second part of 63 relapsed/refractory AML patients,the CI of Ⅱ-Ⅳ°acute GVHD at 100 days was 50.0 ± 8.2%vs 24.1± 8.0%%(P=0.037),and the CI of Ⅲ-Ⅳ° acute GVHD was 16.7 ±6.2%vs 14.8 ± 6.8%(P=0.848),respectively for HID and MSD groups.The Cl of chronic GVHD at two year was 48.0±10.5%vs 39.0±12.2%(P=0.611),and the CI of extensive chronic GVHD was 11.1 ± 6.3%vs 14.6±8.1%(P=0.783),respectively for HID and MSD groups.The CI of CMV infection at one year was 72.2±7.5%vs 40.7±9.5%(P=0.019),and the CI of EBV infection at one year was 52.8± 8.3%vs 18.5 ± 7.5%(P=0.000),respectively for HID and MSD groups.Of the 63 patients,37 patients relapsed after HSCT,and the 3-year CI of relapse was 58.0±9.1%vs 72.5±9.6%(P=0.582),respectively for HID and MSD groups.Eleven patients died of NRM and the CI of NRM at 3 year was 23.8±8.2%vs 18.418.6%(P=0.640),respectively for HID and MSD groups.During a median follow-up of 31.3 months(range,0.4-76 months),18 patients survived and 45 died.The 3-year OS was 33.317.9%vs 28.8±8.9%(P=0.863),and the 3-year RFS was 30.6±7.2%vs 21.6±8.1%(P--0.714),respectively for HID and MSD groups.3.In the third part of 92 elderly AML patients age≥50 years,the CI of Ⅱ-Ⅳ° acute GVHD at 100 days was 44.2 ± 7.6%vs 22.4± 6.0%(P=0.032),and the CI of Ⅲ-Ⅳ° acute GVHD at 100 days was 18.6±5.9%vs 12.2±4.7%(P=0.390),respectively for HID and MSD groups.The CI of chronic GVHD at two year was 45.3±5.7%vs 32.7±6.2%(P=0.290),and the CI of extensive chronic GVHD was 11.3±5.4%vs 18.3±5.9%(P=0.377),respectively for HID and MSD groups.The CI of CMV infection at one year was 65.1±7.3%vs 32.7±6.7%(P=0.004)and the CI of EBV infection at one year was 44.2±7.6%vs 16.3±5.3%(P=0.006),respectively for HID and MSD groups.Of the 93 patients,19 patients relapsed after HSCT,and the 3-year CI of relapse was 23.2±7.2%vs 25.0 ± 6.5%(P=0.850),respectively for HID and MSD groups.Seventeen patients died of NRM,and the 3-year Cl of NRM was 23.8±6.5%vs 15.2±5.3%(P=0.262),respectively for HID and MSD groups.During a median follow-up of 29.6 months(range,0.4-74.8 months),58 patients survived and 34 died.The 3-year OS was 60.2±7.5%vs 65.1 ± 6.8%(P=0.540),and the 3-year RFS was 58.1±7.5%vs 63.3±6.9%(P=0.525),respectively for HID and MSD groups.Conclusion1.As a post remission therapy option for AML,HID-HSCT has similar effectiveness compared to MSD-HSCT;HID-HSCT shows lower incidence of relapse for patients with genetics poor risk AML in CR suggesting a stronger GVL effect2.HID-HSCT shows similar relapse,RFS,OS and NRM compared to those of MSD-HSCT patients with relapsed/refractory AML.As a salvage treatment option for relapsed/refractory AML,HID-HSCT has the same effectiveness as MSD-HSCT.3.HID-HSCT has the same efficacy as MSD-HSCT for elderly patients with AML age≥50 years and it can sever as a safe and effective alternative option for elderly AML patients who lack an MSD. |
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