Granulocyte colony-stimulating factor-supported combined immunosuppressivetherapy (antilymphocyte globulin, cyclosporine, and methylprednisolone) inpatients with aplastic anemia: tolerability, efficacy, and changes in the progenitor cell compartment

Neutropenic infections are the major cause of morbidity and mortality in th e treatment of aplastic anemia (AA) with antilymphocyte globulin (ALG), cyc losporin A (CSA), and methylprednisolone (MP). Recent data suggest a benefi cial effect of administering G-CSF as an adjunct to immunosuppression. We h ave treated 11 consecutive patients with AA using a combined immunosuppress ive regimen including ALG, CSA, and MP plus G-CSF at a dose of 5 mu g/kg/da y until neutropoietic recovery. In addition to measuring routine hematologi cal parameters we have performed serial determinations of reticulocyte coun ts and in vitro progenitor cell cultures before and after therapy in order to assess their predictive value for treatment response and to determine th e impact of therapy on early hematopoiesis. One patient died on day 34 of n eutropenic septicemia. At 1 year, 81% of patients showed response to treatm ent. The median time to ANC values >0.5 and >1.0 x 10(9)/l were 19 and 35 d ays, respectively. Reticulocyte counts started to recover after 6 weeks, an d transfusion independence was observed on day 52 for red blood cell transf usions and on day 53 for platelet concentrates. All patients with detectabl e colony formation in peripheral blood achieved a complete hematological re mission, as compared with only one of five patients without progenitor cell growth. Although normal ranges were rarely achieved, there was a small but definitive improvement in progenitor cell numbers as compared with baselin e values in most patients. Our results confirm the good tolerability and hi gh efficacy of this G-CSF-supported combined immunosuppressive therapy for AA. Detectable colony growth at diagnosis seems to predict a high chance fo r complete hematological response.