Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome.
Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has been proposed to increase the cell dose. We report a prospective randomized study, designed to compare single- vs double-UCB transplantation in children and young adults with acute leukemia in remission or myelodysplasia. Eligible patients had at least two 4-6 HLA-identical UCBs with >3 × 10(7) nucleated cells/kg for the first and >1.5 × 10(7) for the second. The primary end point was the 2-year cumulative incidence of transplantation strategy failure, a composite end point including transplant-related mortality (TRM), engraftment failure, and autologous recovery. Randomized patients who did not proceed to transplantation due to refractory disease were considered transplantation failures. A total of 151 patients were randomized and included in the intent-to-treat analysis; 137 were transplanted. Double-UCB transplantation did not decrease transplantation strategy failure (23.4% ± 4.9% vs 14.9% ± 4.2%). Two-year posttransplant survival, disease-free survival, and TRM were 68.8% ± 6.0%, 67.6% ± 6.0%, and 5.9% ± 2.9% after single-unit transplantation compared with 74.8% ± 5.5%, 68.1% ± 6.0%, and 11.6% ± 3.9% after double-unit transplantation. The final relapse risk did not significantly differ, but relapses were delayed after double-unit transplantation. Overall incidences of graft-versus-host disease (GVHD) were similar, but chronic GVHD was more frequently extensive after double-UCB transplantation (31.9% ± 5.7% vs 14.7% ± 4.3%, P = .02). In an exploratory subgroup analysis, we found a significantly lower relapse risk after double-unit transplantation in patients receiving total body irradiation without antithymocyte globulin (ATG), whereas the relapse risk was similar in the group treated with busulfan, cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell dose remains the standard of care and leads to low TRM. Double-unit transplantation should be reserved for patients who lack such units. This trial was registered at www.clinicaltrials.gov as #NCT01067300.
Department of Pediatric Hematology-Oncology, Assistance Publique-Hôpitaux de Marseille, La Timone Hospital, Aix-Marseille University, Marseille, France; Department of Public Health, Laboratoire de Santé Publique (EA 3279) Research Unit, Marseille University Hospital, Aix-Marseille University, Marseille, France;
Gérard
G
Michel
Department of Pediatric Hematology-Oncology, Assistance Publique-Hôpitaux de Marseille, La Timone Hospital, Aix-Marseille University, Marseille, France;
Claire
C
Galambrun
Department of Pediatric Hematology-Oncology, Montpellier University Hospital, Montpellier, France;
Anne
A
Sirvent
Department of Pediatric Hematology-Oncology, Nancy University Hospital, Nancy, France;
Cecile
C
Pochon
Department of Pediatric Hematology, Jeanne de Flandre Hospital, Lille Nord de France University, Lille, France;
Benedicte
B
Bruno
Department of Pediatric Hematology-Oncology, Bordeaux University Hospital, Bordeaux, France;
Charlotte
C
Jubert
Department of Public Health, Laboratoire de Santé Publique (EA 3279) Research Unit, Marseille University Hospital, Aix-Marseille University, Marseille, France;
Anderson
A
Loundou
Department of Hematology, Huriez Hospital, Lille Nord de France University, Lille, France;
Ibrahim
I
Yakoub-Agha
Department of Hematology, Haut-Leveque Hospital, Bordeaux University Hospital, Pessac, France;
Noel
N
Milpied
Department of Pediatric Hematology-Oncology, Strasbourg University Hospital, Strasbourg, France;
Patrick
P
Lutz
Department of Pediatric Hematology-Oncology, Rouen University Hospital, Rouen, France;
Aude
A
Marie-Cardine
Department of Pediatric Hematology-Oncology, Rennes University Hospital, Rennes, France;
Virginie
V
Gandemer
Department of Hematology-Oncology, Transplant and Cellular Therapy Unit, Paoli-Calmettes Institute, Centre de Recherche en Cancérologie de Marseille and Aix-Marseille University, Marseille, France;
Didier
D
Blaise
Department of Hematology, Edouard Herriot Hospital, Lyon University Hospital, Lyon, France;
Mauricette
M
Michallet
Department of Pediatric Hematology-Oncology, Nantes University Hospital, Nantes, France;
Fanny
F
Rialland
Institute of Pediatric Hematology-Oncology, Lyon University Hospital, Lyon, France;
Cecile
C
Renard
Department of Pediatric Hematology-Oncology, Assistance Publique-Hôpitaux de Marseille, La Timone Hospital, Aix-Marseille University, Marseille, France; Department of Public Health, Laboratoire de Santé Publique (EA 3279) Research Unit, Marseille University Hospital, Aix-Marseille University, Marseille, France;
Claire
C
Oudin
Department of Pediatric Hematology-Oncology, Assistance Publique-Hôpitaux de Marseille, La Timone Hospital, Aix-Marseille University, Marseille, France;
Sophie
S
Esmiol
Clinical Research and Innovation Direction, Assistance Publique-Hôpitaux de Marseille, Marseille, France;
Mylene
M
Seux
Department of Public Health, Laboratoire de Santé Publique (EA 3279) Research Unit, Marseille University Hospital, Aix-Marseille University, Marseille, France;
Karine
K
Baumstarck
Department of Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Université Pierre and Marie Curie, Inserm Unité 938, Paris, France;
Mohamad
M
Mohty
Eurocord, Hôpital Saint Louis AP-HP, University Paris VII, Paris, France; and.
Vanderson
V
Rocha
Department of Pediatric Hematology, AP-HP, Robert Debré Hospital, Paris Diderot University, Paris, France.
Jean-Hugues
JH
Dalle
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D036101:Cord Blood Stem Cell Transplantation; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D006801:Humans; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014916:Whole-Body Irradiation; D055815:Young Adult
D000961:Antilymphocyte Serum