CYTOKINE TREATMENT OF APLASTIC-ANEMIA

The recent discovery and manufacture of recombinant hematopoietic growth factors (cytokines) offers a novel approach to treating patients with aplastic anemia (AA). There are ongoing clinical trials of a number of recombinant proteins, although to date, granulocyte colony-stimulating factor (G-CSF) and granuloryte-macrophage colony-stimulating factor (GM-CSF) have been clinically the most extensively evaluated. Results of these studies suggest that both agents are effective in correcting neutropenia in some patients with AA,but that in general, patients with very severe hypoplasia do not respond to conventional doses of either agent. Our recent study demonstrated that high doses of G-CSF can elevate neutrophil levels in a considerable percentage of patients with very severe hypoplasia. Although multipotential cytokines such as GM-CSF and interleukin-3 were expected to induce a multilineage response in patients with AA, only a few patients have shown any evidence of trilineage recovery following shortterm administration of these agents. On the other hand, long-term administration of cytokines may have different effects. For example, long-term administration of G-CSF with or without cyclosporine has unexpectedly induced trilineage response in some patients. The outcome and adverse reactions associated with long-term therapy with such cytokines must be evaluated in the future.