Unrelated donor marrow transplantation for congenital immunodeficiency and metabolic disease: an update of the experience of the Japan Marrow Donor Program.
We retrospectively analyzed the clinical results of 81 patients with congenital genetic diseases who were treated with bone marrow transplantation (BMT) from unrelated donors identified through the Japan Marrow Donor Program. The patients were aged between 1 and 38 years (median, 4 years). Thirty-five patients underwent transplantation for metabolic disease (MD), ie, mucopolysaccharidosis (n = 25), adrenoleukodystrophy (n = 7), and others (n = 3). The remaining 46 patients had Wiskott-Aldrich syndrome (n = 16), hemophagocytic syndrome including the inherited type (n = 9), severe combined immunodeficiency (n = 6), hyper-IgM syndrome (n = 4), Chédiak-Higashi syndrome (n = 3), Kostmann syndrome (n = 3), and others (n = 5). Fifty-two donor-patient pairs were fully matched at HLA-A, HLA-B, and HLA-DRB1 alleles. The remaining 24 patients received allele-mismatched grafts (20 matched at 5 of 6 loci and 4 matched at 4 of 6 loci). Engraftment occurred in 82.4% of the MD group and 90.7% of the other genetic disease (OGD) group; however, 14 patients (18.2%) experienced either early or late graft failure. The cumulative incidence of grade II to IV acute graft-versus-host disease (GVHD) was 35.5% - 9.8% in the MD group and 47.3% - 9.5% in the OGD group, and the rate of chronic GVHD was 20% in both groups. Forty-nine patients have survived for 3 to 96 months (median, 20 months). The probabilities of 5-year overall survival and event-free survival were 72.6% - 11.5% and 65.3% - 8.6%, respectively, for MD (n = 35) and 72.5% - 7.3% and 63.6% - 7.3% for OGD (n = 46). Although patient status before BMT and the occurrence of grade III to IV acute GVHD significantly affected outcome, unrelated BMT is a curative therapeutic option for children with congenital genetic diseases who have no HLA-matched family donors.
Department of Pediatrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan.
Naoki
N
Sakata
Keisei
K
Kawa
Koji
K
Kato
Hiromasa
H
Yabe
Miharu
M
Yabe
Masayuki
M
Nagasawa
Hideo
H
Mugishima
Hisato
H
Kigasawa
Masahiro
M
Tsuchida
Yuichi
Y
Akiyama
Yasuo
Y
Morisima
Yoshihisa
Y
Kodera
Shunichi
S
Kato
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology* / Q000706:statistics & numerical data; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D030342:Genetic Diseases, Inborn / Q000601:surgery*; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000601:surgery*; D007223:Infant; D008661:Metabolism, Inborn Errors / Q000601:surgery*; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D017211:Treatment Failure