High peripheral blood progenitor cell counts enable autologous backup before stem cell transplantation for malignant infantile osteopetrosis

Autosomal recessive osteopetrosis (OP) is a rare, lethal disorder in which osteoclasts are absent or nonfunctional, resulting in a bone marrow cavity insufficient to support hematopoiesis. Because osteoclasts are derived from hematopoietic precursors, allogeneic hematopoietic cell transplantation can cure the bony manifestations of the disorder. However, high rates of graft failure have been observed in this population. It is not possible to harvest bone marrow from these patients for reinfusion should graft failure be observed. We report that 8 of 10 patients with OP had high numbers of circulating CD34⁺ cells (3% ± 0.9%). This increased proportion of peripheral CD34⁺ cells made it possible to harvest 2 × 10⁶ CD34⁺ cells per kilogram with a total volume of blood ranging from 8.3 to 83.7 mL (1.3-11.6 mL/kg). In addition, colony-forming assays documented significantly more colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid in the blood of osteopetrotic patients compared with controls; the numbers of colony-forming units approximated those found in control marrow. We conclude that OP patients with high levels of circulating CD34⁺ are candidates for peripheral blood autologous harvest by limited exchange transfusion. These cells are then available for reinfusion should graft failure be observed in patients for whom retransplantation is impractical.