Recovery of hematopoietic progenitor cells in patients with severe aplastic anemia who obtained good clinical response with a combination therapy of immunosuppressive agents and recombinant human granulocyte colony-stimulating factor.

Seventeen patients with newly diagnosed acquired severe aplastic anemia were treated with a combination of immunosuppressive drugs consisting of anti-lymphocyte or anti-thymocyte globulin, cyclosporin A (CyA), methylprednisolone, and recombinant human granulocyte colony-stimulating factor (G-CSF). Fourteen (82%) of the 17 patients achieved good response (GR), and 3 (18%) had no response. Among the 14 GR patients, 5 (36%) later evolved clonal diseases, 1 developed myelodysplastic syndrome, and 4 developed paroxysmal nocturnal hemoglobinuria. The numbers of granulocyte-macrophage colony-forming units (CFU-GM) and erythrocyte burst-forming units were markedly low or absent in all cases before therapy. After therapy, those numbers in 13 patients among 14 responders recovered to the level of the normal control at the time of GR. However, the CFU-GM number substantially declined after that but gradually recovered again to reach a normal level over longer clinical courses. The positive rate for HLA-DRB1*1501 was 60% (3/5) among 5 CyA-dependent patients, which tended to be higher than the 20% (1/5) among 5 CyA-independent patients. Thus, immunosuppressive therapy combined with G-CSF provides a high rate of good hematological response accompanied by the apparent recovery of the hematopoietic progenitor compartments.