Diamond-Blackfan Syndrome. I. Erythropoiesis in Prednisone Responsive and Resistant Disease

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Abstract
Summary: We studied the in vitro proliferative characteristics of marrow erythroid progenitors, colony forming unit-erythroid (CFU-E) and burst forming unit-erythroid (BFU-E), in two infants with Diamond-Blackfan syndrome before and during prednisone treatment. Patient 1, had a brisk erythropoietic response to prednisone and the anemia improved; Patient 2 was steroid-unresponsive. Marrow from Patient 1 yielded linear increases in numbers of colonies in erythropoietin dose-response studies, and the magnitude of response was much greater while on prednisone compared to pre-treatment. Cultures of stem cell rich fractions of marrow from Patient 1 separated by unit gravity sedimentation (STA-PUT) revealed moderately reduced CFU-E and BFU-E numbers before prednisone, but normal colony numbers during treatment. Patient 2 differed because CFU-E and BFU-E were almost absent at all erythropoietin doses before and during therapy. Even stem cell rich marrow fractions initially yielded very low colony numbers which did not increase significantly while on prednisone. These findings suggest that in Patient 1 there were adequate numbers of progenitors that were able to differentiate normally only in the presence of prednisone. In Patient 2 the erythropoietic failure in vivo and in vitro was unaffected by prednisone. Speculation: Diamond-Blackfan Syndrome is a heterogeneous disorder with at least two forms demonstrating different patterns of erythropoiesis. In one form erythroid precursors appear to be quantitatively normal but have a relative erythropoietin insensitivity which is correctable with prednisone. In the other form there is either a marked deficiency of numbers of progenitors or an absolute erythropoietin insensitivity.