Experts present an analysis of long term data on the success of stem cell transplantation for osteopetrosis patients which suggests second transplants should be considered a key option.

Osteopetrosis is a rare disease and devastating for those it afflicts. Children born with this genetic disorder may suffer blindness as early as a few months after birth. Hearing loss is also associated with osteopetrosis, as is a tendency to suffer bone fractures.

The problem lies in a disorder of osteoclast function, essentially defective control of bone development, so that bones thicken and overgrow. In the case of blindness, excessive growth of bones at the base of the skull pinches and thus damages the optic nerve. Ultimately, bones thicken to a point that blood cell production ceases. Children born with osteopetrosis may die of bone marrow failure by the age of ten.

Allogeneic hematopoietic stem cell transplantation (HCT), which involves transplantation of human donor stem cells basic to blood generation, offers the best hope for osteopetrosis sufferers. Some medical treatments are available, but have brought mixed results and are not curative.
However stem cell transplantations for this disease are difficult and risky, as demonstrated by a study presented at the European Hematology Association (EHA) congress in Vienna from June, 7 to 10 by Dr Paul Orchard from the University of Minnesota. The study followed outcomes of transplant patients from 1978 to 1999.

Dr Orchard examined long-term survival after HCT in 124 children with infantile osteopetrosis. The median age at transplantation was 8 months, and donors were analyzed according to familial closeness to the recipient. Regardless of donor type, half the patients died within a year of HCT. Dr Orchard says transplantation is greatly complicated by the abnormal architecture of the bone in osteopetrosis sufferers, and consequent difficulties in the ability of new cells to be incorporated into bone marrow. Common causes of death were graft failure (33%), interstitial pneumonitis or adult respiratory distress syndrome (34%), infections (12%) and graft-versus-host disease (10%). The precise cause of lung complications following HCT remains unclear.

The incidence of graft failure is significantly higher than, for example, transplants undertaken for leukemia therapy, where procedures are well-established. Thus a second transplant is an important option for osteopetrosis patients, says Dr Orchard. It is thought that while an initial HCT procedure may fail, implanted cells may open up space in the bone marrow so that a second transplant will then be successful. Life expectancy figures for successful HCT patients are difficult to establish because of limited data, but the first patient treated nearly thirty years ago is still alive. Of the nineteen patients in Dr Orchard’s study who underwent a second transplant for either primary or late graft failure, six have survived.

In general, stem cell transplantation can work well for this disease, says Dr Orchard, and should be undertaken if clinically available. Study of osteopetrosis therapies may also have implications for treatment of genetic metabolic diseases and brain-related inherited diseases involving non-malignant neurological deterioration.

Source: European Hematology Association