Long-term outcomes of total body irradiation plus cyclophosphamide versus busulfan plus cyclophosphamide as conditioning regimen for acute lymphoblastic leukemia: a comparative study

Ann Hematol. 2018 Oct;97(10):1987-1994. doi: 10.1007/s00277-018-3383-9. Epub 2018 Jun 5.

Abstract

The role of total body irradiation (TBI) in allogeneic hematopoietic stem cell transplantation (HCT) for adult acute lymphoblastic leukemia (ALL) remains controversial. Therefore, we investigated long-term treatment outcomes of transplanted ALL patients aiming to identify prognostic factors and the impact of conditioning. We enrolled consecutive ALL patients transplanted from 1990 to 2016, following TBI- or busulfan (Bu)-based conditioning regimen. We studied 151 ALL patients transplanted in first complete remission (CR) (60), other CR (33), or relapsed/refractory disease (58) from sibling (87), and HLA-matched (42) or mismatched (17) unrelated and alternative donors (5). High-dose fractionated TBI-based conditioning was administered in 84. No differences were observed in baseline characteristics, except for disease stage at transplant, donor type, and graft source. With a follow-up of 19.0 (0.5-170.5) in TBI and 14.5 (1.2-319.1) months in non-TBI patients, there was no difference in acute (grades II-IV) or chronic GVHD, thrombotic microangiopathy, and bacterial or fungal infections. Only viral infections were significantly increased in the non-TBI group. There was no significant difference in the cumulative incidence (CI) of treatment-related or relapse mortality and disease-free or overall survival (OS). In the multivariate analysis, unfavorable pre-transplant predictors of OS were age (p = 0.024), advanced disease stage (p = 0.007), and female-to-male donor (p = 0.006). Interestingly, TBI patients younger than 40 years had significantly higher OS (55.1%, p = 0.023) and DFS (48.6%, p = 0.020). In conclusion, high-dose TBI is feasible in younger patients providing better survival. The choice between TBI- or Bu-conditioning regimens remains challenging.

Keywords: Acute lymphoblastic leukemia; Allogeneic; Hematopoietic stem cell transplantation; Total body irradiation.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Adult
  • Age Factors
  • Busulfan / therapeutic use*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / etiology
  • Humans
  • Infections / epidemiology
  • Infections / etiology
  • Kaplan-Meier Estimate
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Remission Induction
  • Retrospective Studies
  • Risk Factors
  • Thrombotic Microangiopathies / epidemiology
  • Thrombotic Microangiopathies / etiology
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Treatment Outcome
  • Whole-Body Irradiation*
  • Young Adult

Substances

  • Cyclophosphamide
  • Busulfan