title: Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002.
abstract: 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.
authors.affiliation: Newcastle General Hospital, Westgate Rd, Newcastle upon Tyne, NE4 6BE United Kingdom. a.r.gennery@ncl.ac.uk
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
authors.forename: Khulood
authors.initials: K
authors.lastname: Khawaja
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.forename: Robbert G M
authors.initials: RG
authors.lastname: Bredius
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Evelina
authors.initials: E
authors.lastname: Mazzolari
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Paul
authors.initials: P
authors.lastname: Landais
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Friedrich
authors.forename: Anders
authors.initials: A
authors.lastname: Fasth
authors.forename: Nico M
authors.initials: NM
authors.lastname: Wulffraat
authors.forename: Susanne
authors.initials: S
authors.lastname: Matthes-Martin
authors.forename: Danielle
authors.initials: D
authors.lastname: Bensoussan
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordigoni
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lange
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagliuca
authors.forename: Marino
authors.initials: M
authors.lastname: Andolina
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cant
authors.forename: E Graham
authors.initials: EG
authors.lastname: Davies
mesh_terms: 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
chemical_list: D007075:Immunoglobulin M; D023201:CD40 Ligand