Semiquantitative assessment of skeletal response to enzyme replacement therapy for Gaucher's disease using the bone marrow burden score.

OBJECTIVE: The purpose of this study was to evaluate the use of a recently described assessment tool to quantify bone marrow response to enzyme replacement therapy in a cohort of adult patients with type 1 Gaucher's disease. MATERIALS AND METHODS: Serial MR images of the femurs, lumbar spine, or both of 57 subjects with a diagnosis of Gaucher's disease, 44 of whom were being treated with enzyme replacement therapy, were evaluated by two musculoskeletal radiologists using the bone marrow burden (BMB) scoring system. This system gives a score out of a possible 8 for the lumbar spine and a score out of a possible 8 for the femurs, so the total BMB score is out of 16. RESULTS: The mean total BMB scores at baseline and final measurement were 13 (95% CI, 12.0-13.8) and 6.5 (95% CI, 5.2-7.9), respectively. Total BMB scores improved by 2-12 points (mean, 6.3 points) for 15 subjects in whom total BMB scores obtained before enzyme replacement therapy and at least one time point after commencement of therapy were available. In 39 subjects for whom only baseline and final femoral BMB scores were available, 24 subjects (62%, 95% CI, 47-76%) improved by 2 or more points while on enzyme replacement therapy. In 24 subjects for whom only baseline and final lumbar BMB scores were available, the BMB score in 16 subjects (67%, 95% CI, 48-85%) improved by 2 or more points. CONCLUSION: The use of the BMB score enabled semiquantitative assessment of bone marrow response to enzyme replacement therapy in adult patients with type 1 Gaucher's disease in Australia. The ability to assess therapy response will facilitate the tailoring of dosage regimens in the future.

Pediatric non-neuronopathic Gaucher disease: presentation, diagnosis and assessment. Consensus statements.

UNLABELLED: Gaucher disease is caused by defective activity of glucocerebrosidase. The resulting accumulation of glucocerebroside in the lysosomes of visceral macrophages in various tissue and organ compartments leads to multiple manifestations, including hepatosplenomegaly, anemia, thrombocytopenia, growth retardation and skeletal disease. The most prevalent form of Gaucher disease is the non-neuronopathic (type 1) variant, which lacks primary involvement of the central nervous system. Traditionally, this has been referred to as the 'adult type'; however, 66% of individuals with symptomatic non-neuronopathic Gaucher disease manifest in childhood. Onset in childhood is usually predictive of a severe, rapidly progressive phenotype and children with non-neuronopathic Gaucher disease are at high risk for morbid complications. Enzyme therapy with recombinant human glucocerebrosidase in childhood can restore health in reversible manifestations and prevent the development of irreversible symptoms. A heightened focus on pediatric Gaucher disease is therefore needed. Although some correlation has been found between genotype and phenotype, mutation analysis is of limited value in disease prognosis. Management of pediatric Gaucher disease should be underpinned by a thorough assessment of the phenotype at baseline with regular monitoring thereafter. Excluding neuronopathic disease is recommended as the first step. Subsequently, baseline evaluation should focus on staging of different storage tissues, particularly the bone the involvement of which results in the greatest long-term morbidity. These organ assessments are recommended because bone disease severity may not correlate with disease severity in other organs and vice versa. In addition, different organs may respond differently to therapy. Initial assessment of each organ system can enable setting of realistic and individualized goals. CONCLUSION: A thorough approach to baseline assessment will improve the understanding of childhood Gaucher disease, optimizing management to minimize impairment of growth and development and prevent irreversible symptoms.

Enzyme replacement therapy for Gaucher's disease: the early Canadian experience.

BACKGROUND: The management of severe Gaucher's disease was dramatically improved by the development of enzyme replacement therapy. However, this treatment is very costly (currently about $21,000 per infusion for adults at the starting dose recommended by the manufacturer). The goal of this study was to determine how enzyme replacement therapy was being prescribed and financially supported in various parts of Canada. In addition, demographic and outcome information was elicited. METHODS: Prescribing physicians were identified through professional associations and with the help of the manufacturer of the enzyme preparations used for the treatment of Gaucher's disease. The physicians were surveyed by questionnaire in July 1995. The study included all patients in Canada who had received enzyme replacement therapy for Gaucher's disease before July 1, 1995. RESULTS: A total of 25 patients (15 children and 10 adults) with type 1 Gaucher's disease, the common nonneuronopathic variant of the disease, were receiving enzyme replacement therapy by the end of 1995. The indications for treatment included massive splenomegaly, growth failure, and severe bony, hematologic and pulmonary complications of the disease; no patients with mild disease were receiving treatment. Treatment regimens varied markedly (from 12 to 160 units of enzyme/kg per month). All the patients were reported to have responded well to therapy, based on serial measurements of hematologic indices, liver and spleen volumes, and numbers of bony crises as well as patients' subjective impressions. Financial support for therapy varied markedly from one province to another. None of the reporting physicians was aware of any patients with severe Gaucher's disease who were denied therapy as a result of inability to pay for the medication. Various agencies provided financial support for therapy, including both federal and provincial governments, private insurance carriers and the commercial supplier of the enzyme. In Ontario provincial health care officials accepted the development, by a multidisciplinary panel of medical experts, of formal guidelines for determining eligibility, on the basis of objective medical criteria, for reimbursement for enzyme replacement treatment. INTERPRETATION: Although some differences were found across the country with respect to the details of treatment, the indications for enzyme replacement therapy and the selection of severely affected patients were similar in the various provinces. However, financial support was inconsistent and varied among provinces and patients. This will prove to be a challenge in future, not only with respect to this disease but also for other diseases for which effective, expensive therapy has been developed.