Cyclosporin-A in severe refractory anemia of myelofibrosis with myeloid metaplasia: a preliminary report.

BACKGROUND AND OBJECTIVE Severe anemia is the outstanding problem in approximately 50 percent of patients with myelofibrosis with myeloid metaplasia (MMM). The present trial was based on the considerations that abnormal immune responses are frequently associated with MMM and that cyclosporin A (Cy-A) has proven to be effective in improving anemia in autoimmune disorders. The aim of this study was to evaluate the effect of Cy-A on anemia of MMM. DESIGN AND METHODS We studied 10 patients with MMM and severe anemia who were not responsive to corticosteroids. Eight of them showed evidence of immune defects (direct or indirect Coombs' test, antinuclear or antimitochondrial antibodies, circulating immune complexes). Cy-A was delivered orally in two refracted doses of 5 mg per kilogram bw every day and the serum level of the drug was maintained between 100 and 200 ng/mL for at least 6 months. Clinical effects were measured by calculating a normalized transfusional need (NTN), and response was defined as about a 30% reduction in the initial transfusion requirement. Hematologic parameters, s-Epo, s-TfR, s-IL2R and lymphocyte flow cytometric analysis were also evaluated. The results were analyzed with the Student's t-test. RESULTS Only 6 patients completed the entire 6 months of planned therapy. Three of these responded, with one no longer needing transfusions. A high CD4/CD8 ratio was predictive of response (mean value 4.7 +/- 3.5 in responders versus 0.9 +/- 0.4 in non-responders, p = 0.06). INTERPRETATION AND CONCLUSIONS An immunomediated mechanism negatively affects erythropoiesis in MMM. Cy-A may be effective for patients with severe refractory anemia in this disease.