HGFs As Adjunctive Therapy To Immunosuppression

The rationale for adding rHuG-CSF to trials of ATG/ALG or cyclosporine was to reduce the morbidity and mortality related to infectious complications during the window of neutropenia before patients exhibited hematologic responses to immunosuppressive therapy. The Severe Aplastic Anemia Working Party of the EBMT conducted a pilot study of 40 patients using rHuG-CSF on d 1-90 in addition to treatment with ALG and cyclosporine, as well as a tapering course of methylprednisolone (153). Compared with previous data, the results showed comparatively favorable trilineage response rates (82%) and actuarial survival (92%), as well as a relatively low number of deaths from infection (8%). In a Gruppo Italiano Trapianti di Milolio Osseo/EBMT update of 100 patients using the same treatment regimen, the 5-yr actuarial survival was similar (87%) (154). Patients not achieving a white count of 5 x 109/L exhibited a relatively lower response rate (37%) and a higher mortality rate (42%), indicating a significant effect of neutrophil counts on response. In a more recent phase 3 randomized study of patients with severe AA by the EBMT, there was no significant difference between groups treated with immunosuppression with or without rHuG-CSF with regard to survival, hematologic responses, and incidence of secondary leukemia (155). Therefore, at least some of the relatively high response and survival rates attributed to rHuG-CSF observed in the 1990s may be owing to other factors, including improvements in supportive care, longer term immunosuppressive regimens, and the addition of cyclosporine to ATG/ALG (109).

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