Engraftment and survival following hematopoietic stem cell transplantation for osteopetrosis using a reduced intensity conditioning regimen

Abstract

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. All six patients who received a bone marrow or peripheral stem cell graft engrafted with 475% 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%. One year after HSCT, six of 11 patients (55%) were surviving. Our data suggest 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 a similar reduced intensity regimen is used.

Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis

“…children affected by OP with a reduced-intensity conditioning regimen (Busulfan, Fludarabine and total lymphoid irradiation) and observed graft failure in 5 children receiving unrelated UCBT, whereas 6 children receiving bone marrow or peripheral blood achieved a sustained engraftment with more than 75% donor cell chimerism 11 .…”

Reduced intensity conditioning is effective for hematopoietic SCT in dyskeratosis congenita-related BM failure

“…Previous reports (Table 3) have described progression of the clinical signs of DKC after transplantation, which was indistinguishable from the natural course of disease. [8][9][10][11][20][21][22][23] In our series, all patients except one received low intensity conditioning regimens. The conditioning protocol was different across different centers.…”

“…Commonly observed transplant-related problems include graft failure, GVHD, sepsis and, more importantly, the increased propensity to develop organ toxicity, namely pulmonary fibrosis, hepatic cirrhosis and veno-occlusive disease, among others. [8][9][10] As a result, long-term survival of persons with DKC following HSCT has been poor. Reduced intensity preparative regimens are less likely to cause organ toxicity and may improve long-term outcomes.…”

“…Reduced intensity preparative regimens are less likely to cause organ toxicity and may improve long-term outcomes. [9][10][11][12] CASE SUMMARIES AND RESULTS Herein, we review nine patients who received allo-SCT at five centers from five different member countries in the Eastern Mediterranean Blood and Marrow Transplantation Registry. Two of these cases were previously published as separate case reports and one as a brief letter.…”

Successful second haploidentical SCT in osteopetrosis

“…Umbilical cord blood transplantation for treatment of OP using a reduced intensity regimen has not been found to be adequate in achieving stable engraftment and results in a high rate of morbidity and mortality. 8 Taking all these considerations into account, we decided to use haploidentical stem cells as a graft source. Historically, the outcome of haploidentical HSCT for treatment of OP has been disappointingly poor, with a survival rate of approximately 25%, although since 1994 there has been a trend for better results.…”