Generalized osteopetrosis: indications, efficacy and peculiarities of hematopoietic stem cell transplantation (own experience)

Generalized osteopetrosis is a rare hereditary disease characterized by systemic sclerosis of the bones of the skeleton, disorder of bone marrow hematopoiesis and, as a consequence, development of severe anemia and appearance of extramedullary hematopoiesis foci in various parenchymal organs. The problem of osteopetrosis is also relevant for the Russian Federation. A radical approach is the allogeneic hematopoietic stem cells transplantation (allo-HSCT). The article presents the experience of treating patients with osteopetrosis in the department of bone marrow transplantation of the Russian Children Clinical Hospital (RCCH).

In the period from 2010 to 2017 allo-HSCT was performed in 6 patients with autosomal recessive form of osteopetrosis. The median age was 5.5 years (1–11 years). Allo-HSCT was performed using the myeloablative regimen of conditioning with treosulfan, fludarabine and melphalan. Reconstitution of donor leukopoiesis was recorded in 5 of 6 patients. In 1 patient, a recipient of umbilical cord blood, there was no reconstitution of donor leukopoiesis. In the early posttransplant period, severe toxic complications were not recorded. One patient had a graft-versus-host reaction, a cutaneous form, I degree. In 5 patients, hypercalcemia was observed in 2–5 months after HSCT, relieved by the admission of bisphosphonates. One patient with a neurodegenerative form of the disease died in the early posttransplant period during deterioration of a hydrocephalic-hypertensive syndrome (donor hematopoiesis was confirmed). In 4 patients with successful allo-HSCT, the follow-up period was from 5 to 42 months (median – 26 months). All patients have complete hematologic recovery, partial correction of the skull deformity, acceleration of growth rates of the body length.

Thus, allo-HSCT is an effective method of systemic disease control. The defeat of the central nervous system is not corrected by allo-HSCT, which requires earlier diagnosis and the initiation of radical therapy before the onset of severe disability. 

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