Long term patterns of humoral and cellular response after vaccination against influenza A (H1N1) in patients with hematologic malignancies

OBJECTIVES: The efficacy of a novel vaccine against influenza virus A (H1N1) in patients with hematologic malignancies is largely unknown. METHODS: We prospectively evaluated the humoral and cellular immune responses after one injection of monovalent adjuvanted 2009 H1N1 vaccine in 47 adults with hematologic malignancies and 77 controls by hemagglutination-inhibition assay and flow-cytometry analysis on day 0, 28, 50 and 90. RESULTS: On day 28 post-vaccination patients had lower seroprotection (95.2% vs 75.2%, p<0.01) and seroconversion (88.7% vs 51.1%, p< 0.01) rates, as well as geometric mean titer (GMT; 256 vs 134, p< 0.05), relative to controls. Response to vaccination varied according to the evaluated time point and the patient status: patients not receiving chemotherapy had seroprotection and GMTs similar to controls in all time-points, while patients receiving chemotherapy or allogeneic hematopoietic stem cell transplant (HSCT) had lower seroprotection and seroconversion levels than controls on day 28 and 50. EMEA cutoffs for efficacy were reached from day 28 by patients in follow-up or under treatment, and only from day 90 by those with HSCT, especially if still under immunosuppressants. Patients treated with immunomodulatory drugs had higher antibody responses in terms of seroprotection and GMTs. T- and NK-cell mediated responses mounted from day 50 and did not differ between patients and controls. CONCLUSIONS: According to EMEA recommendation, H1N1 vaccination strategy was effective at protecting most of hematologic patients, but needed to be improved in those more immunocompromised.