BONE-MARROW TRANSPLANTATION FOR INFANTILE MALIGNANT OSTEOPETROSIS

Purpose: Most patients diagnosed with malignant osteopetrosis die duri ng infancy or early childhood from hemorrhage and infection due to bon e marrow failure. Allogeneic bone marrow transplantation (BMT) has bee n reported to provide curative therapy for this disorder. We report ou r experience with eight patients with malignant osteopetrosis who unde rwent BMT. Patients and Methods: Between May 1957 and August 1992, eig ht children with malignant osteopetrosis underwent allogeneic BMT. Med ian age at BMT was 9 months (range, 2-36 months), Six patients receive d marrow from KLA-identical sibling donors, one from phenotypically ma tched father, and one from a one antigen mismatched father. BMT condit ioning for all patients was busulfan 16 mg/kg and cyclophosphamide 200 mg/kg each administered over 4 days. Graft versus host disease (GVHD) prophylaxis included cyclosporin A in six patients or cyclosporin A a nd methotrexate in two patients. Results: Six patients, including thos e who received bone marrow from their father's, engrafted as documente d by bone marrow biopsy showing an increase in osteoclasts in all case s and by chromosomal analysis in four patients. Two patients died with out engraftment. Three out of six patients engrafted are alive and wel l at the follow-up of 48, 63, and 81 months. Serum calcium, alkaline, and acid phosphatase levels normalized within 2 months. These patients have full bone marrow reconstitution. Serial radiologic studies revea led bone marrow remodelling and a new nonsclerotic bone formation. Vis ion improved dramatically in the youngest patient. Conclusion: BMT off ers cure to patients with malignant osteopetrosis with reconstitution of bone marrow and correction of metabolic disturbances. In our experi ence, reversibility in neurosensory deficit is possible when BMT is do ne at an early age.