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: Paul J Orchard, Anders L Fasth, Jennifer Le Rademacher, Wensheng He, Jaap Jan Boelens, Edwin M Horwitz, Amal Al-Seraihy, Mouhab Ayas, Carmem M Bonfim, Farid Boulad, Troy Lund, David K Buchbinder, Neena Kapoor, Tracey A O'Brien, Miguel A Diaz Perez, Paul A Veys, Mary Eapen
• Journal: Blood (Blood) Vol. 126 Issue 2 Pg. 270-6 (Jul 09 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 26012570 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2015 by The American Society of Hematology.

Topics

• Child
• Child, Preschool
• Female
• Hematopoietic Stem Cell Transplantation (methods, statistics & numerical data)
• Histocompatibility Testing
• Humans
• Infant
• Longitudinal Studies
• Male
• Osteopetrosis (congenital, mortality, therapy)
• Siblings
• Survival Analysis
• Tissue Donors
• Unrelated Donors