Recombinant human erythropoietin (EPO) has been used extensively for over 3 decades to treat anemia, including that associated with cancer treatment. Multiple randomized clinical trials have found that EPO treatment ameliorates anemia and reduces transfusion requirements in cancer patients undergoing chemotherapy. However, reports of some trials suggested that EPO treatment might also exacerbate neutropenia, as anticipated by pre-clinical observations that EPO suppresses neutrophil production in short- and long-term marrow cultures. However, neutropenia was expected in these trials and not reported in detail. Recently, primary data from 5 industry-sponsored trials of EPO treatment in cancer patients became available through the Yale Open Data Access (YODA) project, allowing us to examine serial absolute neutrophil counts (ANCs) from 1650 cancer patients randomized to EPO or placebo treatment. The incidence of severe neutropenia (ANCs <500/mm³ and <200/mm³) during the initial 12 weeks of each trial was determined and found consistently to be greater for study subjects assigned to EPO than to placebo. Study-specific odds ratios for the occurrence of ANCs <500/mm³ (EPO vs. placebo) ranged from 1.24 to 2.08, with a Cochran-Mantel-Haenszel odds ratio for the combined studies of 1.48 (95% confidence interval, 1.08 – 2.03, p=0.014). A statistically significant odds ratio was also found for ANC values of <200/mm³ (1.73, 1.10–2.70, p=0.016), but not for neutropenia overall (ANCs <1500/mm³). These findings indicate that EPO treatment of cancer patients receiving myelosuppressive chemotherapy may be associated with an increased incidence of severe neutropenia.

Erythropoietin, EPO treatment, Neutropenia