Influenza A H1N1 2009 Vaccine in Patients with Hematological Diseases: Good Safety and Immunogenicity Even in Heavily Chemotherapy-Treated Patients

Patients with hematological malignancies are more susceptible for viral infections including influenza, which may be associated with prolonged illness, increased morbidity and mortality. In 2009, the World Health Organization classified the novel influenza A(H1N1) virus as pandemic. The impact of this viral infection in patients (pts) with hematological disorders was unknown, and there were concerns about the risk of serious complications. In Sweden, institutional guidelines recommended two doses of the AS03-adjuvanted inactivated H1N1 split vaccine Pandemrix™ from GlaxoSmithKline in these pts.

Prospectively determine the safety, immunogenicity, and clinical efficacy of influenza A (H1N1) 2009 vaccination in patients with hematological diseases. Compare the immunological response to that obtained by the trivalent seasonal influenza vaccine (TIV).

31 pts were included (myeloma 9, CLL 5, AML 6, ALL 2, CML 2, others 5), out of which 13 had undergone hematopoietic stem cell transplantation (HSCT). All received influenza A(H1N1) 2009 vaccine at day 0, and 28, and the majority (n=25) seasonal influenza vaccine at day 56. Serum for antibody analyses by validated HI-assays was taken at day 0, 28, 56 and 86 and at 1 year. The response to vaccination (seroconversion) was defined as at least a four-fold increase in antibody titer after vaccination or, in case prevaccination HI-titer was < 10, a post-vaccination titer of HI > 40 or greater. Considering that the HI-assay for influenza B differed from the A strains only the seroconversion rate was considered for the influenza B.

The A (H1N1) vaccine was well tolerated and no severe adverse events were reported. At day 28, a total of 16(52%) patients had protective levels of antibodies to A (H1N1) 2009 and 15(48%) had a seroconversion response. After the second dose of the vaccine, 25(81%) reached both protective levels of antibodies and seroconversion. At 1 year, protective levels of antibodies against A (H1N1) 2009 remained in 56% of responding patients. Seroconversion response was observed in 9/13 patients who had undergone HSCT, including 5/9 pts who had been transplanted within1–5 months, as well as in all (n=9) pts with myeloma having advanced disease and/or ongoing intense treatment.

Following vaccination with TIV and evaluated at day 86, protective antibody levels and seroconversion response against A/Brisbane/59/2007 H1N1-like virus were detected in 10(40%) respective 7(28%), and against A/Uruguay/10/2007/H3N2-like virus in 14(56%) respective 10(40%). As for B/Brisbane/60/2008-like virus, seroconversion response was found in 5(20%) of all pts. Response to the pandemic influenza A (H1N1) 2009 vaccine was better than that to the three TIV strains (p<0.001, p<0.009 and p<0.001 respectively).

A substantial proportion of patients with hematological malignancies including even heavily treated Myeloma and HSCT patients mounted a good response to the adjuvanted influenza A (H1N1) 2009 vaccine. This vaccine was well tolerated and had a significantly better immunogenicity than that of the non-adjuvanted seasonal influenza vaccine.

Cherif:GSK: Research Funding. Pauksens:GSK: Research Funding.