Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease.
Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for sickle cell disease (SCD); nevertheless, its use has been limited by the risk of transplantation-related mortality (TRM). Between November 1988 and December 2004, 87 consecutive patients with severe SCD ranging from 2 to 22 years of age received transplants in France. Cerebral vasculopathy was the principal indication for transplantation (55 patients). All the patients received grafts from a sibling donor after a myeloablative conditioning regimen (CR). The only change in the CR during the study period was the introduction of antithymocyte globulin (ATG) in March 1992. The rejection rate was 22.6% before the use of ATG but 3% thereafter. With a median follow-up of 6 years (range, 2.0 to 17.9 years), the overall and event-free survival (EFS) rates were 93.1% and 86.1%, respectively. Graft versus host disease (GVHD) was the main cause of TRM. Importantly, cord blood transplant recipients did not develop GVHD. No new ischemic lesions were detected after engraftment, and cerebral velocities were significantly reduced. The outcome improved significantly with time: the EFS rate among the 44 patients receiving transplants after January 2000 was 95.3%. These results indicate that HLA-identical sibling HSCT after myeloablative conditioning with ATG should be considered as a standard of care for SCD children who are at high risk for stroke.
Bernaudin
Françoise
F
Reference Center for Sickle Cell Disease, Intercommunal Hospital, Créteil, France. francoise.bernaudin@chicreteil.fr
Socie
Gérard
G
Kuentz
Mathieu
M
Chevret
Sylvie
S
Duval
Michel
M
Bertrand
Yves
Y
Vannier
Jean-Pierre
JP
Yakouben
Karima
K
Thuret
Isabelle
I
Bordigoni
Pierre
P
Fischer
Alain
A
Lutz
Patrick
P
Stephan
Jean-Louis
JL
Dhedin
Nathalie
N
Plouvier
Emmanuel
E
Margueritte
Geneviève
G
Bories
Dominique
D
Verlhac
Suzanne
S
Esperou
Hélène
H
Coic
Lena
L
Vernant
Jean-Paul
JP
Gluckman
Eliane
E
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000276:immunology / Q000473:pathology* / Q000601:surgery*; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D042381:Granulocyte Precursor Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome