Bone marrow transplantation for autosomal recessive osteopetrosis A report from the Working Party on Inborn Errors of the European Bone Marrow Transplantation Group

163

130

Summary:A retrospective analysis was made of 122 children who had received an allogeneic haematopoietic stem cell transplantation (HSCT) for autosomal recessive osteopetrosis between 1980 and 2001. The actuarial probabilities of 5 years disease free survival were 73% for recipients of a genotype HLA-identical HSCT (n ¼ 40), 43% for recipients of a phenotype HLA-identical or one HLAantigen mismatch graft from a related donor (n ¼ 21), 40% for recipients of a graft from a matched unrelated donor (n ¼ 20) and 24% for patients who received a graft from an HLA-haplotype-mismatch related donor (n ¼ 41). In the latter group, a trend towards improvement was achieved at the end of the study period (17% before 1994, 45% after 1994, P ¼ 0.11). Causes of death after HSCT were graft failure and early transplant-related complications. Severe visual impairment was present in 42% of the children before HSCT. Conservation of vision was better in children transplanted before the age of 3 months. Final height was related to height at the time of HSCT and better preserved in children transplanted early. Most children attended regular school or education for the visually handicapped. At present, HSCT is the only curative treatment for autosomal recessive osteopetrosis and should be offered as early as possible.

Section: Discussionsupporting

confidence: 68%

Section: Patientsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report

Driessen

Gerritsen

Fischer

et al. 2003

163

130

“…[19][20][21][22] Common reasons for failure have been difficulty in achieving sustained donor engraftment and early transplant mortality from events such as sepsis. OP patients are also prone to severe pulmonary hypertension in the early posttransplant period, with a high risk of respiratory failure following HSCT.…”

Section: Introductionmentioning

confidence: 99%

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

Tolar

Bonfim

Grewal

et al. 2006

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.

“…7 Very few patients with mild AR osteopetrosis successfully grafted at an older age have been described. 8,9 Here, we report good outcomes of two cases with a mild variant of AR osteopetrosis, with a follow-up of 5 and 6 years, respectively, after the BMTs they underwent at 5 and 12 years of age. Informed consent was obtained by parents, and the protocol was approved by the local Medical Ethics Committee.…”

mentioning

confidence: 81%

Long-term follow-up of two children with a variant of mild autosomal recessive osteopetrosis undergoing bone marrow transplantation

Dini

Floris

Garaventa

et al. 2000

Summary:Malignant autosomal recessive (AR) osteopetrosis represents an absolute indication for bone marrow transplantation (BMT). Over the last 15 years, almost 100 BMTs for osteopetrosis have been reported. The median age at transplant of most patients is 4 months. Very few cases of mild AR osteopetrosis have been described. Here, we report the good outcome of two cases of mild AR osteopetrosis with a follow-up of 5 and 6 years, respectively, after an HLA-identical sibling transplant undergone at 5 and 12 years of age, respectively. At the time of BMT, severe visual impairment was present in both children. Bone biopsy demonstrated hypermineralization with virtual obliteration of the medullary spaces, rare microfoci of hematopoiesis and marked deficiency in osteoclastic activity. Successful engraftment was complicated by hypercalcemia, controlled by a combination of bisphosphonate, phosphate infusions, vigorous hydration and calcitonin. Following BMT, radiological and histological findings showed extensive bone resorption with marked augmentation of the osteoclasts in normalized marrow. No improvement was observed in visual acuity, despite complete remodeling of skeletal abnormalities. We conclude that allogeneic BMT is the only chance of curing mild AR osteopetrosis. Bone Marrow Transplantation (2000) 26, 219-224.