Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation.
Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS patients who received transplants between 1979 and 2001 who survived at least 2 years following hematopoietic stem-cell transplantation (HSCT). Events included chronic graft-versus-host disease (cGVHD), autoimmunity, infections, and sequelae of before or after HSCT complications. Three patients (3%) died 2.1 to 21 years following HSCT. Overall 7-year event-free survival rate was 75%. It was lower in recipients of mismatched related donors, also in relation with an older age at HSCT and disease severity. The most striking finding was the observation of cGVHD-independent autoimmunity in 20% of patients strongly associated with a mixed/split chimerism status (P < .001), suggesting that residual-host lymphocytes can mediate autoimmune disease despite the coexistence of donor lymphocytes. Infectious complications (6%) related to splenectomy were also significant and may warrant a more restrictive approach to performing splenectomy in WAS patients. Overall, this study provides the basis for a prospective, standardized, and more in-depth detailed analysis of chimerism and events in long-term follow-up of WAS patients who receive transplants to design better-adapted therapeutic strategies.
Ozsahin
Hulya
H
Department of Pediatrics, Geneva University Hospital, Geneva, Switzerland. ayse.h.ozsahin@hcuge.ch
Cavazzana-Calvo
Marina
M
Notarangelo
Luigi D
LD
Schulz
Ansgar
A
Thrasher
Adrian J
AJ
Mazzolari
Evelina
E
Slatter
Mary A
MA
Le Deist
Francoise
F
Blanche
Stephane
S
Veys
Paul
P
Fasth
Anders
A
Bredius
Robbert
R
Sedlacek
Petr
P
Wulffraat
Nico
N
Ortega
Juan
J
Heilmann
Carsten
C
O'Meara
Anne
A
Wachowiak
Jacek
J
Kalwak
Krzysztof
K
Matthes-Martin
Susanne
S
Gungor
Tayfun
T
Ikinciogullari
Aydan
A
Landais
Paul
P
Cant
Andrew J
AJ
Friedrich
Wilhelm
W
Fischer
Alain
A
D000293:Adolescent; D001327:Autoimmune Diseases / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D003299:Cooperative Behavior; D018572:Disease-Free Survival; D005060:Europe; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007223:Infant; D020127:Recovery of Function / Q000276:immunology*; D012189:Retrospective Studies; D013156:Splenectomy; D015996:Survival Rate; D018183:Transplantation Chimera; D016896:Treatment Outcome; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology* / Q000601:surgery / Q000628:therapy*