Correlation of bone marrow response with hematological, biochemical, and visceral responses to enzyme replacement therapy of nonneuronopathic (type 1) Gaucher disease in 30 adult patients.
PURPOSE: This investigation correlates the marrow response with the degree of increase in hemoglobin (Hb) and platelet count (Plt); decrease in concentrations of plasma tartrate-resistant acid phosphatase, serum angiotensin-converting enzyme (ACE), serum ferritin, and plasma chitotriosidase; and decrease in liver and spleen size, measured by ultrasonography. METHODS: Thirty adult patients with nonneuronopathic (type 1) Gaucher disease (23% splenectomized) were followed for mean periods of 12 and 36 months. RESULTS: The series achieved highly significant mean responses in all hematological, biochemical, and visceral parameters over both observation periods; over a mean 36 months, 19 (63%) had a marrow response, 11 (37%) did not. Six of 7 splenectomized patients attained a marrow response. There were no significant differences between the marrow responders and nonresponders in age, sex, spleen status, Gaucher genotype distribution, mean baseline hematological or biochemical values or liver size, or mean follow-up. At a mean follow-up of 12 months, no significant differences yet were evident between marrow responders and nonresponders in seven of eight response parameters, but marrow responders had a significantly greater reduction in plasma chitotriosidase and a trend toward significantly greater reduction in serum ACE. At a mean follow-up of 36 months, marrow responders had a significantly greater mean increase in Plt and mean decrease in serum ferritin concentration and liver size than did marrow nonresponders; the trend toward greater ACE reduction in marrow responders deepened. However, chitotriosidase response now was equivalent in both subgroups. Marrow nonresponders had a significantly greater mean diminution in spleen size than did marrow responders, but the marrow nonresponders had significantly larger mean spleen size at baseline. Marrow nonresponders also had a greater mean increase in Hb than did marrow responders, but the difference was not significant. The two subgroups had equivalent mean reductions of plasma TRAP. CONCLUSIONS: The clinical relevance of qualitative MRI of the bone marrow in monitoring patients receiving ERT for nonneuronopathic Gaucher disease show that marrow nonresponders can derive considerable benefit from ERT across a variety of other response parameters and suggest an influence of spleen size on marrow response to ERT.