title: Decreased nonrelapse mortality after unrelated cord blood transplantation for acute myeloid leukemia using reduced-intensity conditioning: a prospective phase II multicenter trial.
abstract: A prospective phase II multicenter trial was performed with the aim to obtain less than 25% nonrelapse mortality (NRM) after unrelated cord blood transplantation (UCBT) for adults with acute myeloid leukemia (AML) using a reduced-intensity conditioning regimen (RIC) consisting of total body irradiation (2 Gy), cyclophosphamide (50 mg/kg), and fludarabine (200 mg/m(2)). From 2007 to 2009, 79 UCBT recipients were enrolled. Patients who underwent transplantation in first complete remission (CR1) (n = 48) had a higher frequency of unfavorable cytogenetics and secondary AML and required more induction courses of chemotherapy to achieve CR1 compared with the others. The median infused total nucleated cells (TNC) was 3.4 × 10(7)/kg, 60% received double UCBT, 77% were HLA mismatched (4/6), and 40% had major ABO incompatibility. Cumulative incidence of neutrophil recovery at day 60 was 87% and the cumulative incidence of 100-day acute graft-versus-host disease (II to IV) was 50%. At 2 years, the cumulative incidence of NRM and relapse was 20% and 46%, respectively. In multivariate analysis, major ABO incompatibility (P = .001) and TNC (<3.4 × 10(7)/kg; P = .001) were associated with increased NRM, and use of 2 or more induction courses to obtain CR1 was associated with increased relapse incidence (P = .04). Leukemia-free survival (LFS) at 2 years was 35%, and the only factor associated with decreased LFS was secondary AML (P = .04). In conclusion, despite the decreased NRM observed, other RIC regimens with higher myelosuppression should be evaluated to decrease relapse in high-risk AML. (EUDRACT 2006-005901-67).
authors.affiliation: Service d'Hématologie, Hôtel-Dieu Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Rio
authors.affiliation: Department de Bioinformatique et Statistique Médicale, Hopital Saint-Louis, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.affiliation: Service d'Hématologie, Service d'Hématologie clinique et de thérapie cellulaire, CHU de Bordeaux Hopital du Haut-Lévèque, Pessac, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Vigouroux
authors.affiliation: Service d'Hématologie, Hematology Department, CHU de Nantes, Nantes, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Service d'Hématologie, Service de Greffe de Moelle, Institut Paoli Calmettes, Marseille, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Fürst
authors.affiliation: Service d'Hématologie, Hematologie Clinique, Hopital de l'Archet I, Nice, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Sirvent
authors.affiliation: Service d'Hématologie, Service d'Hématologie Clinique, CHU Estaing, Clermont-Ferrand, France.
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Bay
authors.affiliation: Service d'Hématologie, Hematology-Bone Marrow Transplantation, Hopital Saint-Louis, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Service d'Hématologie, Hôpital Lapeyronie, Montpellier, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Ceballos
authors.affiliation: Service d'Hématologie, Hématologie Clinique, CHU, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Huynh
authors.affiliation: Service d'Hématologie, Hematology, Institut de Cancérologie de la Loire, Loire, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cornillon
authors.affiliation: Service d'Hématologie, CHU Angers, Angers, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Françoise
authors.affiliation: Service d'Hématologie, Hematology, CHU Besançon, Besancon, France.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Legrand
authors.affiliation: Service d'Hématologie, Hematology, CHU de LILLE, Lille, France.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakoub-Agha
authors.affiliation: Department of Hematology, Hôpital La Timone, Marseille, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Michel
authors.affiliation: Service d'Hématologie, CHU Poitiers, Poitiers, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Maillard
authors.affiliation: Service d'Hématologie, CHU Montpellier Pédiatrie, Montellier, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Margueritte
authors.affiliation: Service d'Hématologie, Service d'Hematologie, Hôpital Henri Mondor, Creteil, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Maury
authors.affiliation: Service d'Hématologie, Pitié-Salpêtrière (AP-HP), Paris, France.
authors.forename: Madalina
authors.initials: M
authors.lastname: Uzunov
authors.affiliation: Service d'Hématologie, CHU Grenoble, Grenoble, France.
authors.forename: Claude Eric
authors.initials: CE
authors.lastname: Bulabois
authors.affiliation: Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France.
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Service d'Hématologie, CHU Nancy, Nancy, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Clement
authors.affiliation: Service d'Hématologie, CHU Rennes, Rennes, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Dauriac
authors.affiliation: Service d'Hématologie, CHRU Strasbourg, Strasbourg, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Bilger
authors.affiliation: Service d'Hématologie, Eurocord Office, Hôpital Saint-Louis, Paris, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.affiliation: Service d'Hématologie, Eurocord Office, Hôpital Saint-Louis, Paris, France; Service d'Hématologie, Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ruggeri
authors.affiliation: Service d'Hématologie, Comité Scientifique, SFGM-TC, Hôpital Necker (AP-HP), Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Buzyn
authors.affiliation: Service d'Hématologie, Hôpital Pitié Salpêtrière (AP-HP), Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Nguyen
authors.affiliation: Service d'Hématologie, URC Est Saint Antoine (AP-HP), Paris, France.
authors.forename: Tabassome
authors.initials: T
authors.lastname: Simon
authors.affiliation: Service d'Hématologie, Service d'Hématologie clinique et de thérapie cellulaire, CHU de Bordeaux Hopital du Haut-Lévèque, Pessac, France.
authors.forename: Nöel
authors.initials: N
authors.lastname: Milpied
authors.affiliation: Service d'Hématologie, Eurocord Office, Hôpital Saint-Louis, Paris, France; Department of Haematology, Churchill Hospital, Oxford, United Kingdom. Electronic address: vanderson.rocha@ouh.nhs.uk.
authors.forename: Vanderson
authors.initials: V
authors.lastname: Rocha
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D061349:Unrelated Donors; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
chemical_list: D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Acute myeloid leukemia; Nonrelapse mortality; Reduced-intensity conditioning; Umbilical cord blood transplantation