title: Poor outcome with nonmyeloablative conditioning regimen before cord blood transplantation for patients with high-risk acute myeloid leukemia compared with matched related or unrelated donor transplantation.
abstract: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is recommended for patients with high-risk acute myeloid leukemia (AML). In many situations, a matched related (MRD) or matched unrelated donor (MUD) is lacking, in which case unrelated cord blood units (UCB) provide an alternative. We analyzed the outcome of consecutive high-risk AML patients prepared with reduced-intensity conditioning (RIC) regimens and allografted with UCB (n = 32) and compared their outcome with high-risk AML patients who underwent transplantation with MRD/MUD (n = 49) in the same period of time. Grade III to IV acute graft-versus-host disease (GVHD) occurred slightly more frequently in the UCB group (25%) than in the MRD/MUD group (8%) (P = .069). Conversely, we found a lower incidence of extensive chronic GVHD in the UCB group (6%) than in the MRD/MUD group (20%, P = .085). Nonrelapse mortality at 4 years was 16% and 22% in the UCB and MRD/MUD groups, respectively (P = .529). The cumulative incidence of relapse at 4 years was significantly higher in the UCB group (60%) than in the MRD/MUD group (27%, P = .006). Leukemia-free survival (LFS) and overall survival (OS) at 4 years were 25% and 34%, respectively, in the UCB group and 50% and 56%, respectively, in the MRD/MUD group (LFS, P = .029; OS, P = .072). Multivariate analyses adjusted by cytogenetics and disease status at the time of Allo-HSCT revealed that use of UCB remained an independent predictive factor of shorter LFS (hazard ratio, 2.0; 95% confidence interval, 1.1 to 3.6; P = .018), and was associated with a trend for shorter OS (hazard ratio, 1.7; 95% confidence interval, .9 to 3.2; P = .093). Whereas UCB provides an alternative for patients with high-risk AML lacking an MRD/MUD, the high incidence of relapse after RIC-based UCB Allo-HSCT is a concern. Attempts to improve leukemic control with UCB Allo-HSCT are warranted, as well as the evaluation of other alternative donors in this context.
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; Inserm UMR 1068/Centre de Recherche en Cancérologie de Marseille, Marseille, France. Electronic address: devillierr@ipc.unicancer.fr.
authors.forename: Raynier
authors.initials: R
authors.lastname: Devillier
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France.
authors.forename: Samia
authors.initials: S
authors.lastname: Harbi
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Fürst
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: Crocchiolo
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: El-Cheikh
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Humanitas Cancer Center, Hematology Unit, Instituto Clinico Humanitas, Rozzano, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Castagna
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Etienne
authors.affiliation: Cell Therapy Facility, Institut Paoli Calmettes, Marseille, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Calmels
authors.affiliation: Cell Therapy Facility, Institut Paoli Calmettes, Marseille, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Lemarie
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Inserm UMR 1068/Centre de Recherche en Cancérologie de Marseille, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors.forename: Angela
authors.initials: A
authors.lastname: Granata
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Charbonnier
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rey
authors.affiliation: Aix-Marseille Université, Marseille, France; Inserm UMR 1068/Centre de Recherche en Cancérologie de Marseille, Marseille, France; Cell Therapy Facility, Institut Paoli Calmettes, Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Chabannon
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Faucher
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; Inserm UMR 1068/Centre de Recherche en Cancérologie de Marseille, Marseille, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.affiliation: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; Inserm UMR 1068/Centre de Recherche en Cancérologie de Marseille, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002908:Chronic Disease; D036101:Cord Blood Stem Cell Transplantation; D020732:Cytogenetic Analysis; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D000970:Antineoplastic Agents
keywords: Acute myeloid leukemia; Allogeneic hematopoietic stem cell transplantation; Cord blood transplantation; Reduced-intensity conditioning regimen