Haplo-cord后置模式造血干细胞移植治疗儿童重型再生障碍性贫血的临床分析

Clinical analysis of combining haploidentical donor blood and cord blood stem cell transplantation in the treatment of severe aplastic anemia in children

目的比较是否辅助第三方脐带血在单倍体造血干细胞移植治疗儿童重型再生障碍性贫血的疗效差异。方法回顾性分析2017年5月至2023年2月上海市儿童医院明确诊断为重型或极重型再生障碍性贫血并接受单倍体造血干细胞移植的38例患儿的临床资料。其中21例患儿接受单倍体造血干细胞联合第三方脐血移植(Haplo-cord HSCT),17例接受单倍体造血干细胞移植(Haplo-HSCT)。均采用清髓性预处理方案:氟达拉滨(Flu)/白消安(Bu)/环磷酰胺(Cy)+兔抗人胸腺细胞球蛋白(rabbit anti-human hymocyte globulin,r-ATG)。结果Haplo-cord组21例患儿均获得造血重建,其中2例发生继发性植入失败。Haplo组中1例患儿原发性植入失败,1例继发性植入失败。Haplo-cord组和Haplo组中性粒细胞植入中位时间分别为12(10,19)和11(10,16)d(P=0.630),血小板植入中位时间为16(12,32)和16(13,24)d(P=0.461)。Haplo-cord组和Haplo组Ⅱ-Ⅳ度急性移植物抗宿主病(acute graft-versus-host disease,aGVHD)、Ⅲ-Ⅳ度aGVHD、慢性移植物抗宿主病(chronic graft-versus-host disease,cGVHD)的累积发生率分别为[(23.8±9.3)%比(25±10.8)%,P=0.770]、[(9.5±6.4)%比(18.7±9.8)%,P=0.374]、[(14.3±7.6)%比(33±12.2)%,P=0.226]。两组患儿3年总体生存率(overall survival,OS)、无失败生存率(failure free survival,FFS)、无GVHD/无失败生存率(GVHD-free and failure-free survival,GFFS)分别为[(95.2±4.6)%比(85.6±9.7)%,P=0.405]、[(83.5±8.9)%比(82.4±9.2)%,P=0.642]、[(81±8.6)%比(52.9±12.1)%,P=0.046]。基于短串联重复序列多态性的STR-PCR嵌合检测提示移植后获得造血重建的患儿均为完全单倍体供者嵌合。我们发现Haplo-cord后置模式治疗儿童重型再生障碍性贫血可获得更高的GFFS。结论单倍体造血干细胞移植在治疗儿童重型再生障碍性贫血方面植入率高,疗效确切,辅助输注脐血可能提高移植的总体疗效。

Objective To compare the efficacy of combining haploidentical donor blood and cord blood stem cell transplantation(Haplo-cord HSCT)with haploidentical stem cell transplantation(Haplo-HSCT)in the treatment of severe aplastic anemia(SAA)in children.Methods A retrospective analysis was performed on 38 cases of SAA who underwent haplo-HSCT in Department of Hematology and Oncology of Shanghai Children’s Hospital from May 2017 to February 2023.A total number of 21 children with SAA received Haplo-Cord HSCT,while 17 children received Haplo-SCT.The regimen used myeloablative conditioning(fludarabine,busulfan,cyclophosphamide and rabbit anti-thymocyte globulin).Results No primary graft failure(PGF)occurred in any of the 21 patients in Haplo-cord cohort,and one patient developed PGF in the Haplo cohort.Two patients in Haplo-cord cohort and one patient in Haplo cohort developed Secondary graft failure,respectively.The median time for engraftment for granulocytes in the Haplo core group and Haplo group were 12(10,19)d and 11(10,16)d,respectively(P=0.630).While the median time for platelet implantation in these groups were 16(12,32)and 16(13,24)d,respectively(P=0.461).Patients who underwent an Haplo-cord HSCT had a lower cumulative incidence of GradeⅡtoⅣaGVHD compared with the Haplo HSCT cohort[(23.8±9.3)%vs.(25±10.8)%,P=0.770],they also had lower cumulative incidence of GradeⅢtoⅣaGVHD compared to the Haplo cohort[(9.5±6.4)%vs.(18.7±9.8)%,P=0.374].The cumulative incidence of chronic GVHD was(14.3±7.6)%in Haplo-cord cohort and was(33±12.2)%in Haplo cohort(P=0.226).The 3-year overall,failure-free,and GVHD failure-free(GFFS)survival rates in Haplo-cord cohort and Haplo cohort were[(95.2±4.6)%vs.(85.6±9.7)%,P=0.405],[(83.5±8.9)%vs.(82.4±9.2)%,P=0.642]and[(81±8.6)%vs.(52.9±12.1)%,P=0.046],respectively.We found that cord blood with a high degree of HLA matching and high CD34+cell counts achieved high GFFS.PCR analyses of short tandem repeats(STR)showed persistent and sustained full haplo donor myeloid chimaerism,without any evidence of umbilical cord blood engraftment.We found that Haplo-cord HSCT in children with SAA achieved higher GFFS.Conclusion Haplo-HSCT is an effective treatment for children with SAA,with a high engraftment rate.The co-infusion of an UCB may improve survival of Haplo-HSCT in SAA patients.