Health assessment in patients with autosomal recessive osteopetrosis before and after allogeneic hematopoietic stem cell transplantation

Abstract

Here we report the results of long-term monitoring of children with malignant infantile osteopetrosis (MIOP) before and after a successful hematopoietic stem cell transplantation (HSCT). We present patient health data collected 3-6 years after the completion of treatment, including information on the children's physical and mental health and social adaptation. The study was approved by the Independent Ethics Committee and the Scientifi Council of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation. HSCT is the only currently available radical treatment for MIOP. At the time of the treatment, all the patients exhibited severe visual impairment (descending optic atrophy), transfusiondependent bone marrow dysfunction, hepatosplenomegaly, signifiant skeletal abnormalities and growth retardation. In this study, we included 5 MIOP patients with successful transplantation who had been treated from 2014 to 2018. Four patients underwent HSCT from unrelated 10/10 HLA-identical donors and 1 patient received HSCT from a related 10/10 HLA-identical donor. The ratio of boys to girls was 2:3, the median age at the time of the transplantation was 7 (2–11) years. All the patients demonstrated full donor chimerism after HSCT. Hematopoietic recovery was achieved within the fist 150 days after HSCT. Radiological investigations showed gradual partial reduction of skeletal changes typical of MIOP. All the subjects demonstrated growth of the axial skeleton, facial bone remodeling and abatement of phenotypic features of the disease. The patients' vision remained the same as before HSCT. All the patients reported that their health and quality of life had improved after HSCT. The degree of visual impairment had a substantial impact on the quality of life and social rehabilitation of the patients. The second major factor affcting the quality of life was the development of chronic conditions after HSCT, namely, epilepsy and chronic “graft-versus-host” disease of the lung that require constant medical monitoring and limit rehabilitation potential. The patients' parents gave their consent to the use of their children's data, including photographs, for research purposes and in publications.