General AML

Pre-transplant regimen for autologous SCT in AML patients in CR1 – Busulfan and melphalan or busulfan and cyclophosphamide

Norbert Claude Gorin from Hôpital Saint Antoine, Paris, France, and colleagues from the Acute Leukemia Working Party of the EBMT have previously published a study which indicated superior autologous stem cell transplantation (ASCT) outcomes in a small patient group with acute myeloid leukemia (AML) in first complete remission (CR1) receiving busulfan and melphalan (BUMEL) over busulfan and cyclophosphamide (BUCY) conditioning regimen.1

In the April 2018 issue of the American Journal of Hematology, this group of researchers on behalf of the EBMT conducted a retrospective, multicenter analysis of a larger cohort in order to investigate the same regimens and identify patient subpopulations who can benefit from BUMEL. The primary endpoints of the study were leukemia-free survival (LFS) and post-transplant overall survival (OS). Secondary endpoints were disease relapse incidence (RI) and non-relapse mortality (NRM).2

The study included 1,649 adult de novo AML patients in CR1 with available cytogenetics who underwent ASCT between January 2000 and December 2016 at EBMT centers and received either BUMEL (n = 517) or BUCY (n = 1,137). Based on a primary analysis, patients were divided in two groups: poor risk group with poor cytogenetics and/or harboring FLT3-ITD mutation and non-poor risk group without poor risk cytogenetics.

Key findings:
  • Poor-risk group
    • Patients received BUCY (n = 176) or BUMEL (n = 62)
    • Compared to BUCY, BUMEL associated with a lower RI (HR = 0.52, P = 0.002), better LFS (HR = 0.54, P = 0.002) and OS (HR = 0.61, P = 0.02)
  • Non-poor risk group
    • Patients received BUCY (n = 961) or BUMEL (n = 450)
    • 5-year outcomes in patients in the BUMEL and BUCY arms respectively
      • LFS: 47.6% vs 6%, P = 0.74
      • OS: 60.5% vs 4%, P = 0.68
      • RI: 46.9% vs 2%, P = 0.57
      • NRM: 5.1% vs 8%, P = 0.5

In conclusion, BUMEL showed superior outcomes compared to BUCY and thus, this option should be preferred as conditioning regimen for poor-risk AML patients. In AML patients without poor risk cytogenetics or FLT3 mutation, either BUMEL or BUCY regimens are beneficial conditioning options before ASCT.2

The authors concluded by noting that their study “confirms that ASCT may still be an option to consolidate patients with AML in CR1 at a time when maintenance post-transplant including immune therapies may offer an alternative to allogeneic transplantation with a better quality of life in a carefully selected patient population”.3

References
  1. Gorin N. C. et al. Autologous stem cell transplantation for adult acute myelocytic leukemia in first remission-Better outcomes after busulfan and melphalan compared with busulfan and cyclophosphamide: A retrospective study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Cancer. 2017 Mar 1; 123(5): 824–831. DOI: 10.1002/cncr.30400. Epub 2016 Dec 1.
  2. Gorin N. C. et al. Optimizing the Pretransplant Regimen for Autologous Stem Cell Transplantation in Acute Myelogenous Leukemia : Better Outcomes with Busulfan and Melphalan compared with Busulfan and Cyclophosphamide in high Risk Patients autografted in First Complete Remission. A study from the Acute Leukemia Working Party of the EBMT.. Am J Hemat. 2018 Apr 12. DOI: 10.1002/ajh.25105. [Epub ahead of print].
  3. Gorin N. C. et al. Optimizing the Pretransplant Regimen for Autologous Stem Cell Transplantation in Acute Myelogenous Leukemia : Better Outcomes with Busulfan and Melphalan compared with Busulfan and Cyclophosphamide in high Risk Patients autografted in First Complete Remission. A study from the Acute Leukemia Working Party of the EBMT. Blood. 2017; 130: 338.