Myeloablative conditioning regimens in adult patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission: a systematic review and network meta-analysis

Bone Marrow Transplant. 2023 Feb;58(2):175-185. doi: 10.1038/s41409-022-01865-6. Epub 2022 Nov 10.

Abstract

The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation (allo-HSCT) in complete remission (CR) remain unclear. We performed a systematic review and network meta-analysis to compare the effects of different MAC regimens. Bayesian network meta-analysis was performed using WinBUGS version 1.4.3. The commonly used MAC regimen Bu/Cy (4-day busulfan for toal 16 mg/kg orally or 12.8 mg/kg intravenously, plus 2-day cyclophosphamide for toal 120 mg/kg intravenously) is chosen as the common comparator. Pooled hazard ratios (HRs) with the associated 95% credibility interval (95% CrI) are obtained for all comparisons. We included 19 eligible studies, involving 8104 AML patients and 9 MAC regimens. Compared with Bu/Cy, 3-day busulfan plus fludarabine and thiotepa (Bu3/Flu/TT) is associated with significantly better overall survival (HR, 0.70; 95% CrI, 0.51 to 0.96) and lower risk of relapse (HR, 0.59; 95% CrI, 0.35 to 0.98). Bu3/Flu/TT is also associated with superior overall survival than Cy/TBI (cyclophosphamide plus total body irradiation), and lower risk of relapse than Bu4/Flu (4-day busulfan plus fludarabine). These results suggest that thiotepa-based new MAC regimen Bu3/Flu/TT is associated with improved outcomes in AML patients undergoing allo-HSCT in CR and worth further investigation.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bayes Theorem
  • Busulfan / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Graft vs Host Disease* / etiology
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Leukemia, Myeloid, Acute* / etiology
  • Leukemia, Myeloid, Acute* / therapy
  • Network Meta-Analysis
  • Recurrence
  • Retrospective Studies
  • Thiotepa
  • Transplantation Conditioning / methods
  • Transplantation, Homologous

Substances

  • Busulfan
  • Thiotepa
  • Cyclophosphamide