Bone marrow transplantation for infantile malignant osteopetrosis

Area of Science:

• Pediatric Hematology
• Genetics and Inherited Diseases
• Transplantation Immunology

Background:

• Malignant osteopetrosis is a rare genetic disorder characterized by bone marrow failure, leading to high infant mortality from hemorrhage and infection.
• Allogeneic bone marrow transplantation (BMT) is a potential curative therapy for malignant osteopetrosis.

Purpose of the Study:

• To evaluate the efficacy and outcomes of allogeneic bone marrow transplantation (BMT) in eight patients with malignant osteopetrosis.
• To assess the potential for recovery from bone marrow failure and associated complications.

Main Methods:

• Eight children with malignant osteopetrosis underwent allogeneic BMT between May 1987 and August 1992.
• Conditioning involved busulfan and cyclophosphamide, with GVHD prophylaxis using cyclosporin A +/- methotrexate.
• Graft sources included HLA-identical siblings and partially matched paternal donors.

Main Results:

• Six of eight patients achieved engraftment, confirmed by bone marrow biopsy and chromosomal analysis, with increased osteoclast activity.
• Three engrafted patients remain alive and well at long-term follow-up (48-81 months).
• Metabolic disturbances normalized, bone marrow reconstitution occurred, and radiologic studies showed bone remodeling; vision improved in one patient.

Conclusions:

• Allogeneic bone marrow transplantation (BMT) provides a curative option for malignant osteopetrosis, leading to bone marrow reconstitution and metabolic correction.
• Early intervention with BMT may allow for the reversal of neurosensory deficits.