Comparison of fludarabine/melphalan (FluMel) with fludarabine/melphalan/BCNU or thiotepa (FBM/FTM) in patients with AML in first complete remission undergoing allogeneic hematopoietic stem cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party

Bone Marrow Transplant. 2024 Feb;59(2):247-254. doi: 10.1038/s41409-023-02150-w. Epub 2023 Dec 2.

Abstract

Conditioning protocols for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) are being developed continuously to improve their anti-leukemic efficacy and reduce their toxicity. In this study, we compared the conditioning protocol of fludarabine with melphalan 140 mg/m2 (FluMel) with conditioning protocols based on this same backbone but with an additional alkylating agent i.e., either fludarabine/BCNU (also known as carmustine)/melphalan (FBM), or fludarabine/thiotepa/melphalan (FTM) 110 mg/m2. We included 1272 adult patients (FluMel, n = 1002; FBM/FTM, n = 270) with acute myeloid leukemia (AML) with intermediate/poor cytogenetic risk in first complete remission (CR) from the registry of the EBMT Acute Leukemia Working Party. Despite patients in the FBM/FTM group were older (64.1 years vs. 59.8 years, p < 0.001) and had a worse Karnofsky performance score (KPS < 90, 33% vs. 24%, p = 0.003), they showed a better overall survival (OS) (2 y OS: 68.3% vs. 58.1%, p = 0.02) and less non-relapse mortality (NRM) (2 y NRM: 15.8% vs. 22.2%, p = 0.009) compared to patients treated with FluMel. No significant differences were observed in relapse incidence (RI) (2 y RI: 24.9% vs. 23.7%, p = 0.62). In conclusion, the addition of a second alkylating agent (BCNU/carmustine or thiotepa) to FluMel as FBM/FTM conditioning, improves OS in AML patients in first CR with intermediate/poor risk cytogenetics after allo-HCT.

MeSH terms

  • Adult
  • Alkylating Agents
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Busulfan
  • Carmustine
  • Graft vs Host Disease* / etiology
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Leukemia, Myeloid, Acute*
  • Melphalan / pharmacology
  • Melphalan / therapeutic use
  • Pathologic Complete Response
  • Recurrence
  • Retrospective Studies
  • Thiotepa / pharmacology
  • Thiotepa / therapeutic use
  • Transplantation Conditioning / methods
  • Transplantation, Homologous / adverse effects
  • Vidarabine / analogs & derivatives*

Substances

  • Melphalan
  • Carmustine
  • Thiotepa
  • Busulfan
  • fludarabine
  • Alkylating Agents
  • Vidarabine