title: Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies.
abstract: 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/m(2)/day for 5 days), intravenous busulfan (either 260 mg/m(2): reduced intensity conditioning, or 390-520 mg/m(2): 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.
authors.affiliation: Département d'Hématologie, Institut Paoli Calmettes, Marseille, France Aix-Marseille University, Marseille, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Oudin
authors.affiliation: Centre Hospitalier Universitaire de Nantes, Service d'Hématologie Clinique, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Département d'Hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Furst
authors.affiliation: Centre Hospitalier Universitaire de Nantes, Service d'Hématologie Clinique, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaume
authors.affiliation: Département d'Hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: El Cheikh
authors.affiliation: Centre Hospitalier Universitaire de Nantes, Service d'Hématologie Clinique, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Delaunay
authors.affiliation: Département d'Hématologie, Institut Paoli Calmettes, Marseille, France Humanitas Cancer Center, Hematology Unit, Istituto Clinico Humanitas, Rozzano, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Castagna
authors.affiliation: Département d'Hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Faucher
authors.affiliation: Département d'Hématologie, Institut Paoli Calmettes, Marseille, France.
authors.forename: Angela
authors.initials: A
authors.lastname: Granata
authors.affiliation: Département d'Hématologie, Institut Paoli Calmettes, Marseille, France Aix-Marseille University, Marseille, France Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.
authors.forename: Raynier
authors.initials: R
authors.lastname: Devillier
authors.affiliation: Aix-Marseille University, Marseille, France Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France Cell Therapy Unit, Institut Paoli Calmettes, Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Chabannon
authors.affiliation: Unité de Biostatistiques, Institut Paoli Calmettes, Marseille, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Esterni
authors.affiliation: Département d'Hématologie, Institut Paoli Calmettes, Marseille, France Aix-Marseille University, Marseille, France Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.affiliation: 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.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Département d'Hématologie, Institut Paoli Calmettes, Marseille, France Aix-Marseille University, Marseille, France Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France blaised@ipc.unicancer.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015897:Comorbidity; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D009367:Neoplasm Staging; D012008:Recurrence; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
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