The Clinical Outcomes Of Allogeneic Hematopoietic Stem Cell Transplantation For Severe Aplastic Anemia

Purposes:To analyze the clinical outcomes of severe aplastic anemia(SAA)patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT),to compare the results according to the different antithymocyte immunoglobulin(ATG)/antilymphocyte immunoglobulin(ALG)species,donor source and scheme of haploidentical donor hematopoietic stem cell transplantation(HID HSCT).Methods:Retrospectively collected the clinical data of 83 SAA patients received allo-HSCT in the hematology department of our hospital from January 1,2012 to December 31,2019.According to the ATG/ALG species in the conditioning regimen,patients were divided into porcine anti-human lymphocyte immunoglobulin(p ALG)group(N=64)and rabbit anti-human thymocyte immunoglobulin(rATG)group(N=19).According to the donor sources,patients were divided into matched sibling donor(MSD)group(N=49),HID group(N=26)and unrelated donor(URD)group(N=8).The HID group can be divided into the Beijing protocol group(N=10)and the post-transplantation cyclophosphamide(PTCy)group(N=16)according to the different schemes.The clinical data(including the basic characteristics of patients and donors,transplantation efficacy,survival outcome)of SAA patients in different groups were analyzed.Results:1.The median time of neutrophil and platelet engraftment was 11(7-20)days and 11(6-32)days,respectively.The incidence of grades II-IV acute Gv HD(a Gv HD)and III-IV a Gv HD was 17.16% and 7.37%,logistic regression analysis showed HID was the only risk factor associated with a Gv HD.The cumulative incidence(CI)of chronicGvHD(cGvHD)was 23.1%,while extensive cGvHD was 2.44%.The reactivation of cytomegalovirus(CMV)and epstein-barr virus(EBV)both was 65.1%,and rATG in the conditioning regimen and unmatched donors were risk factors for CMV viremia after transplantation.The incidence of pulmonary infection was 27.7%,while ATG/ALG-related serum sickness and hemorrhagic cystitis was 8.4% and 10.8%,respectively.The estimated 3-year overall survival(OS)was 91.73%.2.The median time of neutrophil engraftment of the p ALG group and rATG cohort was comparable(11 days vs.12 days,P=0.53),while platelet engraftment was relatively prolonged in the rATG group(11 days vs.14 days,P=0.004).The incidence of grades II-IV a Gv HD and grades III-IV a Gv HD were comparable in both groups,but rATG cohort with lower rate of cGvHD and higher incidence of CMV viremia compared with p ALG group(0vs.29.74%,P=0.01;89.5% vs.57.8%,P=0.01).The estimated 3-year OS of p ALG group and the rATG cohort was 89.33% and 100%(P=0.18),respectively.3.The median time of neutrophil and platelet engraftment of the MSD group and HID cohort were comparable(11 days vs.12 days,P=0.08;11 days and 11 days,P=0.84).MSD recipients had a lower incidence of a Gv HD(18.47% vs.47.62%,P=0.01)but comparable incidence of grades II-IV a Gv HD(14.33% vs.27.76%,P=0.22),grades III-IV a Gv HD4.13% vs.15.87%,P=0.08)and cGvHD(21.86% vs.25.86%,P=0.52)compared with HID HSCT patients.The reactivation of CMV occurred in 27(55.1%)MSD and 22(84.6%)HID patients(P=0.01),and the incidence of EBV viremia were 69.4% and 53.8% after transplants,respectively(P=0.18).The estimated 3-year OS of MSD group and HID cohort was 93.39% and 86.57%,respectively(P=0.25).4.The median time of neutrophil engraftment was relatively prolonged in the PTCy group compared with the Beijing protocol group(12 days vs.10.5 days,P=0.006),while the platelet engraftment median time was similar.The incidence of grades II-IV a Gv HD in the Beijing protocol group and the PTCy group was 40.00% and 19.23%(P=0.37),and the CI of cGvHD was 10.00% and 37.14%(P=0.15).The incidence of the CMV reactivation was 80.0% in the Beijing group and 87.5% in the PTCy group(P=0.63),EBV viremia were60.0% and 50.0%,respectively(P=0.93).The estimated 3-year OS of the Beijing protocol group was 66.67%,while PTCy group was 100%(P=0.02).Conclusions:1.SAA patients with rATG in the conditioning regimen resulted in lower incidence of cGvHD compared with p ALG,but virus infection and relatively delayed platelet engraftment after transplantation need to be focused on.2.SAA patients received HID HSCT achieved similar incidence of grades II-IV a GVHD and OS compared with MSD HSCT,so HID HSCT is an effective and safe option for SAA patients,especially those in urgent need of treatment but without MSD or refractory to IST.3.SAA patients underwent HID HSCT with PTCy protocol had a relatively prolonged neutrophil engraftment median time but better OS compared with the Beijing protocol,these conclusions still needs to be verified.