The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population.

Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01 / F. Bonifazi, C. Pavoni, J. Peccatori, F. Giglio, M. Arpinati, A. Busca, P. Bernasconi, A. Grassi, A. Paola Iori, F. Patriarca, L. Brunello, C. Di Grazia, A. Michele Carella, D. Cilloni, A. Picardi, A. Proia, S. Santarone, R. Sorasio, P. Carluccio, P. Chiusolo, A. Cupri, M. Luppi, C. Nozzoli, D. Baronciani, M. Casini, G. Grillo, M. Musso, F. Onida, G. Palazzo, M. Parma, S. Tringali, A. Vacca, D. Vallisa, N. Sacchi, E. Oldani, A. Masciulli, A. Gheorghiu, C. Girmenia, M. Martino, B. Bruno, A. Rambaldi, F. Ciceri. - In: BONE MARROW TRANSPLANTATION. - ISSN 1476-5365. - 57:6(2022 Jun), pp. 949-958. [10.1038/s41409-022-01626-5]

Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01

M. Luppi
Membro del Collaboration Group
;
F. Onida
Membro del Collaboration Group
;
A. Rambaldi
Membro del Collaboration Group
;
2022

Abstract

The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population.
Settore MED/15 - Malattie del Sangue
apr-2022
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/932745
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