Engraftment and Survival Following Hematopoietic Stem Cell Transplantation for Osteopetrosis Using a Reduced Intensity Conditioning Regimen.

Autosomal recessive osteopetrosis (OP) is a disease characterized by osteoclast dysfunction, leading to multisystem morbidity and death of most affected children. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for OP, but this patient population is particularly prone to post-transplant complications and death after myeloablative conditioning. To determine the potential of achieving improved overall outcomes in these patients by decreasing pre-transplant mortality, we investigated engraftment and survival following a reduced intensity regimen including busulfan, fludarabine and total lymphoid irradiation. We report outcomes in 11 patients:

Legend: NC, nucleated cell; URD, unrelated donor; REL, related donor; BM, bone marrow; UCB, umbilical cord blood; PBSC, peripheral blood stem cells; engr., engraftment; NK, not known; HLA matching is reported for 6 antigens. All six patients who received a bone marrow or peripheral stem cell graft engrafted with > 75% donor chimerism. In contrast, all five recipients of unrelated cord blood as a stem cell source for a first graft failed to demonstrate donor hematopoietic chimerism. The day 100 and 6 month mortality was low at 9%. At 1-year after HSCT, 6 of 11 patients (55%) were surviving. Our data suggests that this regimen results in low peri-transplant mortality without compromising engraftment when a marrow or peripheral stem cell graft is used. An umbilical cord blood graft, however, should be used with caution for patients with OP when this or similar reduced intensity regimen is used.