Clinical value of bone marrow cultures in childhood pure red cell aplasia

We assessed the value of marrow cultures for defining the pathophysiology, diagnosis, and therapeutic response to immunosuppressive therapy in childhood pure red cell aplasia (PRCA).

Patients were evaluated either at diagnosis (n = 23) or at the time of treatment failure (n = 2). Twelve patients had transient erythroblastopenia of childhood (TEC), 4 had Diamont-Blackfan anemia (DBA), and 9 had acquired sustained PRCA (A-Su-PRCA). Bone marrow mononuclear cells were cultured with combination of human recombinant (rhu) erythropoietin (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.

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 substantially lower in the remaining patients than in controls (45.5 +/- 15.4 versus 91.7 +/- 12.7, p < 0.05). Addition of SCF restored erythropoiesis 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; of the 5, 3 had or developed some evidence of myelodysplasia.

Our data indicate that in vitro colony studies might prove to be a useful diagnostic tool, because erythropoiesis' poor response to growth factors, including SCF, may suggest the diagnosis of myelodysplasia. Moreover, it may have predictive value; in cases of PRCA, regardless of etiology, poor growth of erythropoietic colonies may predict refractoriness to immunomodulating therapy.