Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002.
CD40 ligand (CD40L) deficiency causes recurrent sinopulmonary infection, Pneumocystis carinii pneumonia, and Cryptosporidium parvum infection. Approximately 40% to 50% of patients survive to the third decade: long-term survival is unclear. Hematopoietic stem cell transplantation (HSCT) is curative. We present a retrospective analysis of 38 European patients undergoing HSCT for CD40L deficiency in 8 European countries between 1993 and 2002. Donor stem cell source included 14 HLA-identical siblings, 22 unrelated donors, and 2 phenotypically matched parental stem cells (12 T-cell depleted). Of the patients, 34 engrafted and 26 (68%) survived; 3 had autologous reconstitution, 22 (58%) were cured, and 1 engrafted but has poor T-cell immune reconstitution. There were 18 evaluated patients who responded to vaccination. Of the patients, 12 (32%) died from infection-related complications, with severe cryptosporidiosis in 6. Grades 2 to 4 graft-versus-host disease (GvHD) associated with infection occurred in 6 of 12 fatal cases. HSCT cured 58% of patients, 72% of those without hepatic disease. Early T-cell function following whole marrow HSCT may limit cryptosporidial disease, but survival was similar after T-cell-depleted HSCT. Preexisting lung damage was the most important adverse risk factor. Further studies will determine optimal timing and type of HSCT.
Gennery
Andrew R
AR
Newcastle General Hospital, Westgate Rd, Newcastle upon Tyne, NE4 6BE United Kingdom. a.r.gennery@ncl.ac.uk
Khawaja
Khulood
K
Veys
Paul
P
Bredius
Robbert G M
RG
Notarangelo
Luigi D
LD
Mazzolari
Evelina
E
Fischer
Alain
A
Landais
Paul
P
Cavazzana-Calvo
Marina
M
Friedrich
Wilhelm
W
Fasth
Anders
A
Wulffraat
Nico M
NM
Matthes-Martin
Susanne
S
Bensoussan
Danielle
D
Bordigoni
Pierre
P
Lange
Andrzej
A
Pagliuca
Antonio
A
Andolina
Marino
M
Cant
Andrew J
AJ
Davies
E Graham
EG
D000293:Adolescent; D000328:Adult; D023201:CD40 Ligand / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003625:Data Collection; D005060:Europe; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D006942:Hypergammaglobulinemia / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D007075:Immunoglobulin M; D007223:Infant; D009894:Opportunistic Infections / Q000209:etiology; D012189:Retrospective Studies
D007075:Immunoglobulin M; D023201:CD40 Ligand