Hematopoietic stem cell transplantation for infantile osteopetrosis

Abstract

• Hematopoietic cell transplantation results in long-term survival.• Primary graft failure is very high and the predominant cause of death.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 HLAmismatched 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 5 .01 and P 5 .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 5 .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. (Blood. 2015;126(2):270-276)

Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis

“…This is in keeping with what has been published previously 10 , especially with the use of mismatched donors.…”

“…In our group of patients, the overall survival at 6 years was 43%, a result consistent with those of previously published studies on HSCT from donors other than an HLA-identical HSCT from different types of donor reported a 10-year OS of 39% using donors other than an HLA-identical sibling 10 .…”

“…Our data shows a high incidence of graft failure after UCBT (33%), which, however, is comparable to that reported by Orchard et al, who found a 1-year probability of graft failure of 34%; in that cohort graft rejection accounted for 43% of deaths in patients transplanted from a donor other than an HLA-identical sibling 10 .…”

“…The role of conditioning regimen in facilitating engraftment in children with OP is not fully elucidated, since in general these patients are treated with a myeloablative preparative regimen due to the poor quality of engraftment with the use of RIC protocols 10 . In our series all patients have been treated with a myeloablative regimen and 84% of them received a full dose of Busulfan.…”

Practice Patterns and Preferences Among Hematopoietic Cell Transplantation Clinicians

“…For example, the BMT CTN 0201 study showed equivalent survival after allogeneic transplantation when peripheral blood or bone marrow was used as a source of stem cells, with a higher risk of chronic GVHD after peripheral blood stem cell grafts [8]. A subsequent analysis confirmed that peripheral blood stem cell grafts were associated with inferior long-term health-related quality of life and reduced rates of return to work, compared with those after bone marrow grafts [9]. Nonetheless, for several reasons, the field had already moved towards an increased use of peripheral blood grafts before publication and dissemination of the BMT CTN 0201 results, and it is not clear that these results will significantly alter this trend [10].…”