Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.

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Publication Details

Journal
Blood Cancer Journal
Published
2024-08-21
DOI
https://doi.org/10.1038/s41408-024-01116-5
Citations
8
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
3.64

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article

Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial

Carmen Di Grazia, Angelo Michele Carella, Elena Oldani, Luca Castagna et al.
8 citations
Blood Cancer Journal
Acute Myeloid Leukemia Research
3.64
article

Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial

Carmen Di Grazia, Angelo Michele Carella, Elena Oldani, Luca Castagna, Attilio Olivieri, Paolo Bernasconi, Domenico Russo, Chiara Pavoni, Maria Caterina Micò, Alessandro Busca, Giuseppe Marotta, Elisabetta Terruzzi, Patrizia Chiusolo, Pellegrino Musto, Paolo Rivela, Raffaella Cerretti, Paolo Corradini, Alessandro Rambaldi, Fabrizio Pane, Riccardo Saccardi, Francesca Patriarca, Giorgia Saporiti, Anna Paola Iori, Giuseppe Milone, Anna Grassi, Carlo Borghero, Irene Cavattoni, Nicola Mordini, Stella Santarone, Andrea Bacigalupo, Gianluca Cavallaro, Arnon Nagler
article en
8 citations

Abstract

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.

Blood Cancer JournalVol. 14(1)
Marche Polytechnic University (IT), University of Milan (IT), Sheba Medical Center (IL), Casa Sollievo della Sofferenza (IT), Policlinico Umberto I (IT), Agostino Gemelli University Polyclinic (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Ospedale di Bolzano (IT), Ospedale Vincenzo Cervello (IT), Ospedale Papa Giovanni XXIII (IT), Azienda Ospedaliera San Gerardo (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Ospedale Santa Maria della Misericordia di Udine (IT), Policlinico Universitario di Catania (IT), Azienda Ospedaliera Universitaria Senese (IT), Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT), Policlinico Tor Vergata (IT), Ospedale Policlinico San Martino (IT), Azienda USL di Pescara (IT), Policlinico San Matteo Fondazione (IT), Ospedale San Bortolo (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo (IT), University of Bari Aldo Moro (IT), University of Brescia (IT)
Associazione Italiana per la Ricerca sul Cancro, Agenzia Italiana del Farmaco, Ministero della Salute
Openalex Percentile: Top 7%
Acute Myeloid Leukemia Research
3.64
DOIOpen Access PDFOpenAlex
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