Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients

Autor: Bilal Mohty, Michael Bel, Marija Vukicevic, Monika Nagy, Emmanuel Levrat, Sara Meier, Stephane Grillet, Christophe Combescure, Laurent Kaiser, Yves Chalandon, Jakob Passweg, Claire-Anne Siegrist, Eddy Roosnek, the Blood and Marrow Transplant Program
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: Haematologica, Vol 96, Iss 6 (2011)
Druh dokumentu: article
ISSN: 0390-6078
1592-8721
DOI: 10.3324/haematol.2011.040386
Popis: Background Responses to influenza vaccines are poorly characterized in immunocompromised patients. The goal of this study was to assess the efficacy of the AS03-adjuvanted influenza H1N1/A/09 vaccine in allogeneic hematopoietic stem cell transplant recipients.Design and Methods We enrolled 65 patients and 138 controls in an open prospective study. Controls received one dose and patients 2 doses of the AS03-adjuvanted influenza H1N1/A/09 vaccine at a 3-week interval. Geometric mean titers and seroprotection/seroconversion rates were determined by hemagglutination inhibition before and four weeks after the last immunization. Clinical and biological markers, including immunoglobulins, CD3+, CD4+, CD8+ and naïve CD4+ T-cell counts were assessed in all patients.Results Baseline seroprotection rates were low in patients (6.6%) and controls (14.8%). After 2 doses, patients (n=57, 92.3%) achieved similar seroprotection rates (84% vs. 87%, P=0.65) and antibody titers (305 vs. 340, P=0.88) as controls (n=131, 93.9%) after one dose. In univariate analysis, transplant-to-vaccination interval less than 12 months, active graft-versus-host disease, immunosuppressive drugs, hemoglobin less than 12g/L, lymphopenia less than1G/L, IgG less than 4g/L, IgA less than 0.5g/L, IgM less than 0.5g/L and naive CD4+ T cells less than 150/μL were significantly associated with weaker responses. Multivariate analysis identified transplant-to-vaccination interval and active graft-versus-host disease as the most powerful negative predictors of antibody responses (P=0.04 and P=0.002, respectively). Vaccination was well tolerated in both cohorts.Conclusions In allogeneic hematopoietic stem cell transplant recipients, 2 doses of an adjuvanted influenza vaccine elicited comparable responses to a single dose in healthy individuals. However, vaccine responses remained poor in patients with ongoing graft-versus-host disease, supporting the need for additional strategies in this high-risk patient population. (ClinicalTrials.gov Identifier: NCT01022905)
Databáze: Directory of Open Access Journals
Externí odkaz: