Erythropoietin Treatment Is Associated with Augmented Immune Response to the Influenza Vaccine in Hematologic Patients.

Recombinant human erythropoietin (EPO) has been effective in treating various types of anemia. EPO receptors on non-erythroid cells suggest that EPO may also have non-erythroid effects. Indeed, we have previously shown that EPO has anti-neoplastic immunomodulating effects in both patients and mice (Mittelman PNAS 2001; Mittelman Eur J Haematol 2004). EPO effects were demonstrated in both the cellular and humoral immune systems (Katz Acta Haematol 2005; Katz Eur J Immunol 2007; Prutchi-Sagiv Br J Haematol 2006; Prutchi-Sagiv Exp Hematol 2008; Lifshitz Mol Immunol 2009). Hassan et al. (Ren Fail 2003) have reported that patients with renal failure treated with EPO had a higher antibody (Ab) titer in response to the Hepatitis B vaccine. We therefore hypothesized that EPO plays a general role in augmenting the immune response. To test this hypothesis we examined the effect of EPO on the antibody response to the seasonal influenza (flu) vaccine.

Three groups, all receiving the flu vaccine, were tested: A) Healthy controls (HC), B) Hematologic patients not receiving EPO (H-NoEPO), C) Hematologic patients on EPO for anemia (H-EPO). Mean ages of the participants [95% CI] were 59.5 [56.5-62.4], 59.6 [50.9-68.2], and 73.9 [68.8-79.0] respectively. Flu vaccine and EPO were ordered by the attending physicians only, irrespective of the study. Blood samples were drawn prior to and 3 weeks, 7 weeks and 4 months after the flu vaccination. Anti-flu Ab titer was measured using the complement fixation test. The results are presented as the number (percentage) of tested individuals who responded with at least two- or four-fold increase in anti-flu titers, compared to their baseline. P value represents comparison of H-EPO to H-NoEPO.

Of the HC individuals, 90% doubled (at least) and 58% quadrupled their anti-flu Ab titers. Of the H-NoEPO patients only 56% doubled and 19% quadrupled their titers. However, 72% of the H-EPO patients doubled and 56% quadrupled their titers, a response approaching that of healthy controls, despite their being significantly older.

1) Hematologic patients respond poorly to the flu vaccine, compared to healthy subjects. 2) EPO treatment is associated with an improved immune response to the flu vaccine in hematologic patients. This suggests that EPO may serve as an immune augmenting agent for the flu vaccine and possibly other vaccines as well.

Off Label Use: Non erythroid effects: immune, anti-cancer (all under investigation). Prutchi-Sagiv:BioGAL- Start up (inactive): Equity Ownership. Mittelman:BioGAL- Start up (inactive): Equity Ownership, Patents & Royalties.