As in MDS, rHuEPO can synergize with rHuG-CSF to increase the rate of multilin-eage responses in patients with AA; however, such responses have generally not been sustained, and rHuEPO ± rHuG-CSF therapy has generally not been considered a useful regimen. In one study, combined rHuG-CSF and rHuEPO therapy elicited erythroid responses in 6/14 (43%) patients with moderate AA after 10 wk, and a delayed response was noted in 3 additional patients (145). Erythroid responses were less impressive among individuals with severe AA (3/13, 23%). Durable trilineage responses were observed in 6/27 (22%) patients, but in 5 of these patients, count improvement was not manifest until after 10 wk of therapy. In this study, rHuG-CSF 400 |g/m2 iv daily and rHuEPO 100 U/kg sc daily were considered to be doses sufficient to increase neutrophil counts and Hb concentrations, respectively. In another trial of 20 patients, rHuG-CSF (50-100 |g/m2 sc daily) with addition of rHuEPO (2000-8000 U/m2 three times weekly), started 2 wk after rHuG-CSF initiation, resulted in red cell transfusion independence in 7 (35%) patients with long-term administration, with at least bilineage responses seen in the same proportion of patients (146). A multicenter randomized, controlled study compared rHuG-CSF alone with two dosages of rHuEPO (200 U/kg or 400 U/kg three times weekly) in addition to rHuG-CSF (147). Erythroid responses in the 400-U/kg rHuEPO group were significantly higher (36.8%) than either the lower dose rHuEPO group (14.6%) or the rHuG-CSF-alone group (12.9%); however, red cell transfusion independence was not observed. Factors predicting response included nonsevere AA, lower serum EPO, higher Hb concentration, reticulocyte count, and level of serum transferrin receptors.

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