title: Hematopoietic stem cell transplantation for infantile osteopetrosis.
abstract: We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLA-mismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5- and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P = .01 and P = .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P = .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed.
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN;
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: Department of Pediatrics, Sahlgrenska University Hospital, Gothenburg, Sweden;
authors.forename: Anders L
authors.initials: AL
authors.lastname: Fasth
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, and Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Le Rademacher
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, and.
authors.forename: Wensheng
authors.initials: W
authors.lastname: He
authors.affiliation: Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, Netherlands;
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Boelens
authors.affiliation: Blood and Marrow Transplant Program, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, OH;
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Horwitz
authors.affiliation: Department of Pediatric Hematology Oncology, King Fasial Specialist Hospital & Research Center, Riyadh, Saudi Arabia;
authors.forename: Amal
authors.initials: A
authors.lastname: Al-Seraihy
authors.affiliation: Department of Pediatric Hematology Oncology, King Fasial Specialist Hospital & Research Center, Riyadh, Saudi Arabia;
authors.forename: Mouhab
authors.initials: M
authors.lastname: Ayas
authors.affiliation: Bone Marrow Transplant Program, Hospital de Clinicas-Universidade Federal do Paraná, Curitiba, Brazil;
authors.forename: Carmem M
authors.initials: CM
authors.lastname: Bonfim
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY;
authors.forename: Farid
authors.initials: F
authors.lastname: Boulad
authors.affiliation: Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN;
authors.forename: Troy
authors.initials: T
authors.lastname: Lund
authors.affiliation: Department of Pediatrics, Children's Hospital of Orange County, Orange, CA;
authors.forename: David K
authors.initials: DK
authors.lastname: Buchbinder
authors.affiliation: Department of Research Immunology/Bone Marrow Transplant, Children's Hospital of Los Angeles, Los Angeles, CA;
authors.forename: Neena
authors.initials: N
authors.lastname: Kapoor
authors.affiliation: Cord & Marrow Transplant Program, Sydney Children's Hospital, Sydney, Australia;
authors.forename: Tracey A
authors.initials: TA
authors.lastname: O'Brien
authors.affiliation: Servicio de Oncohematologia, Hospital Infantil Universitario Nino Jesus, Madrid, Spain; and.
authors.forename: Miguel A Diaz
authors.initials: MA
authors.lastname: Perez
authors.affiliation: Blood and Marrow Transplant Program, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Veys
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, and.
authors.forename: Mary
authors.initials: M
authors.lastname: Eapen
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000706:statistics & numerical data; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D010022:Osteopetrosis / Q000151:congenital / Q000401:mortality* / Q000628:therapy*; D035781:Siblings; D016019:Survival Analysis; D014019:Tissue Donors; D061349:Unrelated Donors