CLINICAL-VALUE OF BONE-MARROW CULTURES IN CHILDHOOD PURE RED-CELL APLASIA

Purpose: We assessed the value of marrow cultures for defining the pat hophysiology, diagnosis, and therapeutic response to immunosuppressive therapy in childhood pure red cell aplasia (PRCA). Patients and Metho ds: Patients were evaluated either at diagnosis (n = 23) or at the tim e of treatment failure (n = 2). Twelve patients had transient erythrob lastopenia of childhood (TEC), 4 had Diamont-Blackfan anemia (DBA), an d 9 had acquired sustained PRCA (A-Su-PRCA). Bone marrow mononuclear c ells were cultured with combination of human recombinant (rhu) erythro poietin (EPO), granulocyte monocyte colony stimulating factor (GM-CSF) , granulocyte colony stimulating factor (G-CSF), Interleukin 3 (IL-3), either with or without stem cell factor (SCF), and burst forming unit of erythroid (BFU-E) growth was assessed. Results: The combination of growth factors without SCF failed to induce any erythropoiesis (BFU-E <10/10(5) mononuclear cells) in 10 patients (2 with TEC, 2 with DBA, and 6 with A-Su-PRCA), although the growth of erythroid colonies was s ubstantially lower in the remaining patients than in controls (45.5 +/ - 15.4 Versus 91.7 +/- 12.7, p <0.05). Addition of SCF restored erythr opoiesis in all but 6 patients (5 with A-Su-PRCA and 1 with DBA). Five of 6 nonresponders did not respond to any immunomodulating therapy; o f the 5, 3 had or developed some evidence of myelodysplasia. Conclusio n: Our data indicate that in vitro colony studies might prove to be a useful diagnostic tool, because erythropoiesis' poor response to growt h factors. including SCF, may suggest the diag nosis of myelodysplasia . Moreover, it may have predictive value, in cases of PRCA, regardless of etiology, poor growth of erythropoietic colonies may predict refra ctoriness to immunomodulating therapy.