Haploidentical-versus identical-sibling transplant for high-risk pediatric AML:A multi-center study

Background:Human leukocyte antigen-identical sibling donor(ISD)-hematopoietic stem cell transplantation(SCT)is a potentially curative treatment for high-risk pediatric acute myeloid leukemia(AML).A haploidentical donor(HID)is readily available to almost all children.Previous studies have demonstrated that patients with HID-SCT had similar outcomes compared to ISD-SCT for pediatric and adult AML.However,the role of HID-SCT in high-risk pediatric AML is unclear.Methods:To compare the overall survival of high-risk AML children who underwent either HID-SCT or ISD-SCT,we analyzed 179 cases of high-risk AML patients under 18 years of age treated with either ISD-SCT(n=23)or HID-SCT(n=156).Granulocyte colony-stimulating factor plus anti-thymocyte globulin-based regimens were used for HID-SCT.We also analyzed the subgroup data of AML patients at first complete remission(CR1)before SCT with known cytogenetic risk.Results:The numbers of adverse cytogenetic risk recipients were 8(34.8%)and 13(18.8%)in the ISD-SCT group and the HID-SCT group,and the number of patients with disease status beyond CR1 were 6(26.1%)and 14(20.3%)in the two groups.The cumulative rates of grades II-IV acute graft-versus-host disease(GVHD)were 13.0%in the ISD-SCT group and 34.8%in the HID-SCT group(P=0.062),with a three-year cumulative rates of chronic GVHD at 14.1%and 34.9%,respectively(P=0.091).The relapse rate in the ISD-SCT group was significantly higher than that in the HID-SCT group(39.1%vs.16.4%,P=0.027);with non-relapse mortality at 0.0%and 10.6%(P=0.113),respectively.The three-year overall survival rates were 73.0%for the ISD-SCT group and 74.6%for the HID-SCT group(P=0.689).In subgroup analysis,the three-year relapse rate in the ISD-SCT group was higher than that in the HID-SCT group(50.0%vs.9.2%,P=0.001)and the three-year DFS in the ISD-SCT group(50.0%)was lower than that in the HID-SCT group(81.2%)(P=0.021).Conclusions:Unmanipulated HID-SCT achieved DFS and OS outcomes comparable to those of ISD-SCT for high-risk pediatric AML patients with potentially higher rate but manageable GVHD.

Optimized therapeutic strategy for patients with refractory or relapsed acutemyeloid leukemia:long-term clinical outcomes and health-related quality of life assessment

Background:Patients with refractory or relapsed acute myeloid leukemia(AML)have poor survival,necessitating the exploration of optimized therapeutic strategy.Here,we aimed to investigate clinical outcomes and health-related quality of life(HR-QoL)after total therapy,which included allogeneic hematopoietic stem cell transplantation(allo-HSCT),and prophylactic donor lymphocyte infusion(DLI)in the early phase after transplantation,followed bymultiplemeasurable residual disease(MRD)and graft-versus-host disease(GvHD)-guided DLIs.Methods:Consecutive patients who had refractory or relapsed AML and had received non-T-cell-depleted allo-HSCT at Peking University Institute of Hematology were included in the study.If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse,severe infection,organ failure,and active GvHD at the time of planned DLI,prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen(HLA)-matched related HSCT or at 45-60 days after transplantation for haploidentical or unrelated HSCT.Subsequently,multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation.Results:A total of 105 patients were eligible.Eighty-seven patients received prophylactic DLI(group B),while 18 did not receive prophylactic DLI(group A).Among 105 patients,the cumulative incidence of grade 2-4 acute GvHD and chronic GvHDwas 40.6%(95%confidence interval[CI]=30.6%-50.6%)and 73.3%(95%CI=67.4%-79.2%),respectively.The cumulative incidence of relapse(CIR),transplant-related mortality(TRM),and leukemia-free survival(LFS)at 5 years after transplantation were 31.5%(95%CI=21.9%-41.1%),22.1%(95%CI=11.3%-32.9%),and 46.4%(95%CI=36.8%-56.0%),respectively.In group B,the CIR,TRM,and LFS at 5 years after transplantation were 27.6%(95%CI=17.6%-37.6%),21.6%(95%CI=11.2%-32.0%),and 50.8%(95%CI=40.0%-61.6%),respectively.At the end of follow-up,48 patients survived,and more than 90%of survivors had satisfactory recoveries of HR-QoL.Conclusions:Our study indicated that total therapy is not only associated with decreased CIR,comparable TRM,and better long-term LFS,but also with satisfactoryHR-QoL for refractory or relapsed AML,compared with those of standard of care therapy reported previously.Therefore,total therapymay be an optimized therapeutic strategy for refractory or relapsed AML.