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

Zhonghua Xue Ye Xue Za Zhi. 2024 Mar 14;45(3):249-256. doi: 10.3760/cma.j.cn121090-20230822-00084.
[Article in Chinese]

Abstract

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 grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively (P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD 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 grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.

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。.

Keywords: Acute lymphocytic leukemia; Conditioning regimen; Stem cell transplantation; Total body irradiation.

Publication types

  • English Abstract

MeSH terms

  • Adult
  • Cyclophosphamide / administration & dosage
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Prognosis
  • Survival Rate
  • Transplantation Conditioning* / methods
  • Transplantation, Homologous*
  • Whole-Body Irradiation*

Substances

  • Cyclophosphamide