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FLAMSA-Based Reduced-Intensity Conditioning versus Myeloablative Conditioning in Younger Patients with Relapsed/Refractory Acute Myeloid Leukemia with Active Disease at the Time of Allogeneic Stem Cell Transplantation: An Analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

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2020

Authors

Rodríguez-Arbolí, Eduardo
Labopin, Myriam
Tischer, Johanna
Brecht, Arne
Ganser, Arnold
Finke, Jürgen
Blau, Igor Wolfgang
Kröger, Nicolaus
Kalhs, Peter
Forcade, Edouard

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American Society for Transplantation and Cellular Therapy. Editor comercial: Elsevier Inc.
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The use of myeloablative conditioning (MAC) in the setting of active relapsed/refractory (R/R) acute myeloid leukemia (AML) has been hindered by high historical rates of nonrelapse mortality (NRM). FLAMSA (fludarabine, Ara-C, and amsacrine) chemotherapy (CT) followed by reduced-intensity conditioning (RIC) has been proposed as an effective and potentially safer alternative in this scenario. As improvements in supportive care have contributed to decreasing NRM rates after MAC, a comparative reassessment of these two strategies was performed. This was a registry-based analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Eligibility criteria included age 18 to 50 years, primary refractory, first or second relapsed active AML, first allogeneic stem cell transplantation from a matched sibling donor (MSD) or an unrelated donor (UD) performed between 2005 and 2018, MAC or FLAMSA-RIC. A total of 1018 patients were included. The median patient age was 39 years (range, 18 to 50). Two hundred and fifty-eight patients received busulfan (Bu)/cyclophosphamide (Cy), 314 received Cy/total body irradiation (TBI), 318 received FLAMSA-TBI, and 128 received FLAMSA-CT. The median duration of follow-up was 50 months. In univariate analysis, the 2-year relapse incidence (RI) (54%; 95% confidence interval (CI), 50%-57%), leukemia-free survival (LFS) (30%; 95% CI, 27%-33%), and refined graft-versus-host disease-free, relapse-free survival (GRFS) (21%; 95% CI, 18%-24%) were not significantly different between cohorts. Lower 2-year NRM was observed in the FLAMSA-CT group (7% versus 16% in Bu/Cy, 19% in Cy/TBI, and 18% in FLAMSA-TBI; P = .04), as well as increased 2-year overall survival (OS) (50% versus 33% in Bu/Cy, 34% in Cy/TBI, and 36% in FLAMSA-TBI; P = .03). These results were maintained in the multivariate analysis (hazard ratio [HR] for NRM: .40, P = .01; HR for OS: .65, P = .01; Bu/Cy as reference). These data suggest that FLAMSA-CT may be a preferred conditioning regimen in patients with active R/R AML due to lower NRM. Yet, the high relapse rates observed in our analyses emphasize the need for novel therapeutic strategies in this clinical setting.

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Medical Subject Headings::Persons::Persons::Age Groups::Adolescent
Medical Subject Headings::Persons::Persons::Age Groups::Adult
Medical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Bone Marrow
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Alcohols::Glycols::Butylene Glycols::Busulfan
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Retrospective Studies
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunosuppression::Transplantation Conditioning
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Young Adult
Medical Subject Headings::Diseases::Immune System Diseases::Graft vs Host Disease
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Hematopoietic Stem Cell Transplantation
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Myeloid::Leukemia, Myeloid, Acute

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Keywords

Acute myeloid leukemia, Allogeneic stem cell transplantation, Reduced-intensity conditioning, Sequential conditioning, Leucemia mieloide aguda, Trasplante de células madre

Citation

Rodríguez-Arbolí E, Labopin M, Tischer J, Brecht A, Ganser A, Finke J et al. FLAMSA-Based Reduced-Intensity Conditioning versus Myeloablative Conditioning in Younger Patients with Relapsed/Refractory Acute Myeloid Leukemia with Active Disease at the Time of Allogeneic Stem Cell Transplantation: An Analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2020 Nov;26(11):2165-2173