Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency.
Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.
Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom.
Amel
A
Hassan
Claire
C
Booth
Alex
A
Brightwell
Zoe
Z
Allwood
Paul
P
Veys
Kanchan
K
Rao
Manfred
M
Hönig
Wilhelm
W
Friedrich
Andrew
A
Gennery
Mary
M
Slatter
Robbert
R
Bredius
Andrea
A
Finocchi
Caterina
C
Cancrini
Alessandro
A
Aiuti
Fulvio
F
Porta
Arnalda
A
Lanfranchi
Michela
M
Ridella
Colin
C
Steward
Alexandra
A
Filipovich
Rebecca
R
Marsh
Victoria
V
Bordon
Saleh
S
Al-Muhsen
Hamoud
H
Al-Mousa
Zobaida
Z
Alsum
Hasan
H
Al-Dhekri
Abdulaziz
A
Al Ghonaium
Carsten
C
Speckmann
Alain
A
Fischer
Nizar
N
Mahlaoui
Kim E
KE
Nichols
Eyal
E
Grunebaum
Daifulah
D
Al Zahrani
Chaim M
CM
Roifman
Jaap
J
Boelens
E Graham
EG
Davies
Marina
M
Cavazzana-Calvo
Luigi
L
Notarangelo
H Bobby
HB
Gaspar
D000243:Adenosine Deaminase / Q000172:deficiency / Q000276:immunology; D000361:Agammaglobulinemia / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D035781:Siblings; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D061349:Unrelated Donors
D019653:Myeloablative Agonists; D000243:Adenosine Deaminase