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This study investigated the immune response to 2009 pandemic H1N1 influenza monovalent vaccine in children with cancer receiving chemotherapy.We enrolled 25 pediatric patients. Ten patients younger than 10 years old received two vaccinations and the remaining 15 patients older than 10 years old received one. We checked hemagglutination-inhibition (HAI) antibody titers in sera of patients before and 3–4 weeks after vaccination. Seroprotective titer was defined as HAI antibody titer ≥40 and seroresponse as ≥4-fold increase in HAI antibody titers after vaccination.The pre- and post-vaccination seroprotective rates were 52% and 72% (P = 0.24). Sixteen (64%) patients were possibly exposed to 2009 pandemic H1N1 influenza previously, and there was significant association between possible exposure and pre-vaccination seroprotective rate (P = 0.03). Post-vaccination seroresponse rate was 32%, and seroresponse was greater in patients without pre-vaccination seroprotective titer than those with pre-vaccination seroprotective titer (50% vs. 15%, P = 0.07). Children with lymphocyte counts above 1,500/μl during vaccination period had better seroresponse than those with lymphocyte counts below 1,500/μl (P = 0.008). Post-vaccination geometric mean titer (GMT) significantly increased in patients younger than 10 years receiving two vaccinations (pre- and post-vaccination GMT were 21.4 and 60.6, respectively; P = 0.025).Monovalent vaccine for the 2009 pandemic H1N1 influenza A was found to be partially immunogenic in children with cancer, as evidenced by 32% of seroresponse rate. Immune response can be improved with vaccinations administered to patients whose absolute lymphocyte counts returned to a level of 1,500/μl or higher. Pediatr Blood Cancer 2011; 57: 1154–1158. © 2011 Wiley Periodicals, Inc.