Treosulfan-based or busulfan-based conditioning for allogeneic transplantation: the role of dose intensity
Mené dans 5 pays européens (France, Allemagne, Hongrie, Italie et Pologne) sur 476 patients atteints d'une leucémie myéloïde aiguë ou d'un syndrome myélodysplasique, cet essai de phase III évalue la non infériorité, du point de vue de la survie sans événement 2 ans après la greffe allogénique de cellules souches hématopoïétiques, du tréosulfan par rapport au busulfan, utilisés comme traitement de conditionnement en combinaison avec la fludarabine (durée médiane de suivi : 15,4 mois)
Allogeneic haematopoietic stem-cell transplantation (HSCT) is a potentially curative therapy for patients with acute myeloid leukaemia or myelodysplastic syndrome. The role of dose intensity of the conditioning regimen in the outcome of HSCT has been extensively investigated. Conditioning regimens have been historically divided into myeloablative conditioning regimens, such as the combination of high-dose cyclophosphamide with total-body radiation or with high-dose busulfan, and reduced-intensity conditioning regimens, for which the combination of fludarabine with a reduced-dose of busulfan is the most commonly used regimen. Only relatively young (up to 50–55 years) and medically fit patients are eligible for myeloablative conditioning regimens, whereas reduced-intensity conditioning was designed to allow treatment of older and less fit patients. Several new myeloablative conditioning regimens with reduced toxicity have been designed based on fludarabine with myeloablative doses of an alkylator drug, such as busulfan, trying to provide safer myeloablation. Several retrospective comparisons have shown that reduced-intensity conditioning regimens decrease transplantation-related mortality but relapse is increased resulting in similar overall survival to myeloablative conditioning. However, these retrospective analyses have an inherent selection bias due to the different characteristics of patients eligible for each modality. Only properly designed randomised studies can determine the optimal conditioning regimen. Although very few such studies have been done in the field of stem cell transplantation, several important studies have been published in the past 10 years.
The Lancet Haematology , commentaire, 2018