Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies
Claire Oudin,
Patrice Chevallier,
Sabine Furst,
Thierry Guillaume,
Jean El Cheikh,
Jacques Delaunay,
Luca Castagna,
Catherine Faucher,
Angela Granata,
Raynier Devillier,
Christian Chabannon,
Benjamin Esterni,
Norbert Vey,
Mohamad Mohty,
Didier Blaise
Affiliations
Claire Oudin
Département d’Hématologie, Institut Paoli Calmettes, Marseille, France;Aix-Marseille University, Marseille, France
Patrice Chevallier
Centre Hospitalier Universitaire de Nantes, Service d’Hématologie Clinique, France
Sabine Furst
Département d’Hématologie, Institut Paoli Calmettes, Marseille, France
Thierry Guillaume
Centre Hospitalier Universitaire de Nantes, Service d’Hématologie Clinique, France
Jean El Cheikh
Département d’Hématologie, Institut Paoli Calmettes, Marseille, France
Jacques Delaunay
Centre Hospitalier Universitaire de Nantes, Service d’Hématologie Clinique, France
Luca Castagna
Département d’Hématologie, Institut Paoli Calmettes, Marseille, France;Humanitas Cancer Center, Hematology Unit, Istituto Clinico Humanitas, Rozzano, Milano, Italy
Catherine Faucher
Département d’Hématologie, Institut Paoli Calmettes, Marseille, France
Angela Granata
Département d’Hématologie, Institut Paoli Calmettes, Marseille, France
Raynier Devillier
Département d’Hématologie, Institut Paoli Calmettes, Marseille, France;Aix-Marseille University, Marseille, France;Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France
Christian Chabannon
Aix-Marseille University, Marseille, France;Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France;Cell Therapy Unit, Institut Paoli Calmettes, Marseille, France
Benjamin Esterni
Unité de Biostatistiques, Institut Paoli Calmettes, Marseille, France
Norbert Vey
Département d’Hématologie, Institut Paoli Calmettes, Marseille, France;Aix-Marseille University, Marseille, France;Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France
Mohamad Mohty
Centre Hospitalier Universitaire de Nantes, Service d’Hématologie Clinique, France;Université de Nantes, Faculté de Médecine, France;INSERM CRNCA UMR 892, Nantes, France;Centre d’Investigation Clinique en Cancérologie (CI2C), Nantes, France;Service d’Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, Paris, France;Université Pierre et Marie Curie, Paris, France;INSERM, UMRs 938, Paris, France
Didier Blaise
Département d’Hématologie, Institut Paoli Calmettes, Marseille, France;Aix-Marseille University, Marseille, France;Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France
The introduction of reduced intensity/toxicity conditioning regimens has allowed allogeneic hematopoietic cell transplantation to be performed in patients who were previously considered too old or otherwise unfit. Although it led to a reduction in non-relapse mortality, disease control remains a major challenge. We studied the outcome of 165 patients with acute myeloid leukemia (n=124) or myelodysplastic syndrome (n=41) transplanted after conditioning with fludarabine (30 mg/m2/day for 5 days), intravenous busulfan (either 260 mg/m2: reduced intensity conditioning, or 390–520 mg/m2: reduced toxicity conditioning), and rabbit anti-thymoglobulin (2.5 mg/kg/day for 2 days). The median age of the patients at transplantation was 56.8 years. The 2-year relapse incidence was 29% (23% versus 39% for patients transplanted in first complete remission and those transplanted beyond first complete remission, respectively; P=0.008). The 2-year progression-free survival rate was 57% (95% CI: 49.9–65). It was higher in the groups with favorable or intermediate cytogenetics than in the group with unfavorable cytogenetics (72.7%, 60.5%, and 45.7%, respectively; P=0.03). The cumulative incidence of grades 2–4 and 3–4 acute graft-versus-host disease at day 100 was 19.3% and 7.9%, respectively. The cumulative incidence of chronic graft-versus-host disease at 1 year was 21.6% (severe forms: 7.8%). Non-relapse mortality at 1 year reached 11%. The 2-year overall survival rate was 61.8% (95% CI: 54.8–69.7). Unfavorable karyotype and disease status beyond first complete remission were associated with a poorer survival. This well-tolerated conditioning platform can lead to long-term disease control and offers possibilities of modulation according to disease stage or further development.