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Randomized Controlled Trial
. 2024 Aug 21;14(1):141.
doi: 10.1038/s41408-024-01116-5.

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

Gianluca Cavallaro  1 , Anna Grassi  1 , Chiara Pavoni  1 , Maria Caterina Micò  1 , Alessandro Busca  2 , Irene Maria Cavattoni  3 , Stella Santarone  4 , Carlo Borghero  5 , Attilio Olivieri  6 , Giuseppe Milone  7 , Patrizia Chiusolo  8 , Pellegrino Musto  9 , Riccardo Saccardi  10 , Francesca Patriarca  11 , Fabrizio Pane  12 , Giorgia Saporiti  13 , Paolo Rivela  14 , Elisabetta Terruzzi  15 , Raffaella Cerretti  16 , Giuseppe Marotta  17 , Angelo Michele Carella  18 , Arnon Nagler  19 , Domenico Russo  20 , Paolo Corradini  21 , Paolo Bernasconi  22 , Anna Paola Iori  23 , Luca Castagna  24 , Nicola Mordini  25 , Elena Oldani  1 , Carmen Di Grazia  26 , Andrea Bacigalupo  27 , Alessandro Rambaldi  28
Affiliations
Randomized Controlled Trial

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

Gianluca Cavallaro et al. Blood Cancer J. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Non-relapse mortality.
Non-relapse mortality (NRM) at year 4 and 10 after transplantation of the entire study population (A); Non-relapse mortality at 4 and 10 years in patients younger than 51 years (B); Non-relapse mortality at 4 and 10 years in patients older than 51 years (C).
Fig. 2
Fig. 2. Causes of death.
Death events in patients older 51 years old in the first year after transplant.
Fig. 3
Fig. 3. Cumulative incidence of relapse.
A Cumulative incidence of relapse (CIR) at 10 years in the entire study population; B Cumulative incidence of relapse at 10 years in patients younger than 51 years; C Cumulative incidence of relapse at 10 years in patients older than 51 years.
Fig. 4
Fig. 4. Leukemia Free and Overall Survival.
Leukemia-free survival (LFS) at 10 years in the entire study population (A); Leukemia-free survival in patients younger than 51 (B); Leukemia-free survival in patients older than 51 (C); Overall survival (OS) at 10 years in the entire study population (D); Overall survival in patients younger than 51 (E); Overall survival in patients older than 51 (F).
See this image and copyright information in PMC

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