含全身放射治疗预处理方案异基因造血干细胞移植治疗成人急性淋巴细胞白血病的疗效分析

Efficacy of allogeneic hematopoietic stem cell transplantation based on a total body irradiation conditioning treatment regimen for adult acute lymphocytic leukemia

目的比较含全身放射治疗(TBI)和仅基于化疗预处理方案的异基因造血干细胞移植(allo-HSCT)治疗成人急性淋巴细胞白血病(ALL)的疗效,探讨影响预后的相关因素。方法收集2015年1月至2022年8月于联勤保障部队第九六〇医院血液病科接受allo-HSCT治疗的95例成人ALL患者的临床资料,根据预处理方案不同分为TBI/环磷酰胺组(TBI/Cy组,53例)和白消安/环磷酰胺组(Bu/Cy组,42例)。比较两组在造血重建、移植相关并发症、移植后复发率、非复发死亡率(NRM)、总生存(OS)率、无白血病生存(LFS)率等方面的差异,并对预后影响因素进行分析。结果TBI/Cy组、Bu/Cy组中性粒细胞植入中位时间分别为14(10~25)d、14(10~24)d(P=0.106),血小板植入中位时间分别为17(10~42)d、19(11~42)d(P=0.488);Ⅱ~Ⅳ度急性移植物抗宿主病(aGVHD)累积发生率分别为41.5%、35.7%(P=0.565),Ⅲ/Ⅳ度aGVHD累积发生率分别为24.5%、4.8%(P=0.009),重度慢性移植物抗宿主病(cGVHD)的发生率分别为16.7%、13.5%(P=0.689);巨细胞病毒(CMV)血症发生率分别为41.5%、35.7%(P=0.565),EB病毒血症发生率分别为34.0%、35.7%(P=0.859),重度感染发生率分别为43.4%、33.3%(P=0.318),出血性膀胱炎发生率分别为20.8%、50.0%(P=0.003)。TBI/Cy组、Bu/Cy组中位随访时间分别为37.1、53.3个月,移植后2年累积复发率分别为17.0%、42.9%(P=0.017),NRM分别为24.5%、7.1%(P=0.120),LFS率分别为58.5%、50.0%(P=0.466),OS率分别为69.8%、64.3%(P=0.697)。多因素分析显示,预处理方案含TBI是allo-HSCT后复发的保护性因素(HR=0.304,95%CI 0.135~0.688,P=0.004),而对NRM的影响不显著(HR=1.393,95%CI 0.355~5.462,P=0.634);感染是成人ALL患者allo-HSCT后OS的独立危险因素。结论含TBI预处理方案与基于化疗预处理方案allo-HSCT治疗成人ALL比较,Ⅲ/Ⅳ度aGVHD发生率较高,出血性膀胱炎发生率及复发率较低。

Objective To analyze the efficacy of allo-HSCT with total body irradiation(TBI)and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis.Methods The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included.According to the conditioning regimen,the patients were divided into two groups:the TBI plus cyclophosphamide(TBI/Cy)group(n=53)and the busulfan plus cyclophosphamide(Bu/Cy)group(n=42).Hematopoietic reconstitution after transplantation,GVHD,transplantation-related complications,relapse rate(RR),non-relapse mortality(NRM),OS,and LFS were compared,and the factors related to prognosis were analyzed.Results The median time of neutrophil engraftment was 14(10-25)days in the TBI/Cy group and 14(10-24)days in the Bu/Cy group(P=0.106).The median time of megakaryocyte engraftment was 17(10-42)days in the TBI/Cy group and 19(11-42)days in the Bu/Cy group(P=0.488).The incidence of gradeⅡ-Ⅳacute GVHD(aGVHD)in the TBI/Cy and Bu/Cy groups was 41.5%and 35.7%,respectively(P=0.565).The incidence of gradeⅢ-ⅣaGVHD in these two groups was 24.5%and 4.8%,respectively(P=0.009).The incidence of severe chronic GVHD in the two groups was 16.7%and 13.5%,respectively(P=0.689).The incidence of cytomegalovirus infection,Epstein-Barr virus infection,severe infection,and hemorrhagic cystitis in the two groups was 41.5%and 35.7%(P=0.565),34.0%and 35.7%(P=0.859),43.4%and 33.3%(P=0.318),and 20.8%and 50.0%(P=0.003),respectively.The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups,respectively.The 2-year cumulative RR was 17.0%in the TBI/Cy group and 42.9%in the Bu/Cy group(P=0.017).The 2-year cumulative NRM was 24.5%and 7.1%,respectively(P=0.120).The 2-year LFS was 58.5%and 50.0%,respectively(P=0.466).The 2-year OS rate was 69.8%and 64.3%,respectively(P=0.697).In the multivariate analysis,the conditioning regimen containing TBI was a protective factor for relapse after transplantation(HR=0.304,95%CI 0.135-0.688,P=0.004),whereas the effect on NRM was not significant(HR=1.393,95%CI 0.355-5.462,P=0.634).Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL.Conclusion allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL,compared with chemotherapy regimen.While the incidence o gradeⅢ/ⅣaGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.