Safety and Immunogenicity of High Dose Trivalent Inactivated Influenza Vaccine in Pediatric Patients with Acute Lymphoblastic Leukemia

Influenza is an important cause of morbidity and mortality worldwide. Most deaths outside the elderly population are seen in other high risk groups, such as immunocompromised individuals. Compared to the general population, children with cancer have a higher frequency of influenza infections, have symptoms lasting twice as long and are more likely to require hospitalization, all of which may lead to delays in their chemotherapy. It is recommended that children with cancer receive a yearly trivalent influenza vaccine (TIV) and studies show that children with acute lymphoblastic leukemia (ALL) do mount an immune response to the TIV, although they often have lower titers and seroresponse rates compared to healthy controls. Recently, a high dose (HD) TIV was found to provide a statistically significant increase in the level of antibody response in elderly patients compared to the standard dose (SD) TIV. We hypothesized that the HD TIV would be well tolerated and more immunogenic compared to the SD TIV in pediatric patients with ALL.

This was a randomized, double-blind, phase I safety and immunogenicity trial comparing HD to SD TIV in children with ALL aged 3–17 years, at least one month into chemotherapy and in 1^stcomplete remission. Subjects were randomized 2:1 to receive either 0.5mL of HD (60ug per antigen) or SD (15ug per antigen) 2010–11 or 2011–12 TIV. Local and systemic reactions were collected for 7 days after each vaccination. HAI titers to influenza virus antigens as well as complete blood count, quantitative CD4, CD8, CD19 and serum IgG levels were measured before and 28–35 days after vaccination. In year 1, no blood was drawn before dose 2 if a second dose was required.

50 subjects were enrolled (20 in year 1, 30 in year 2). Mean age was 8.25 years (range 4.7 – 12.3 years) and 62% were male. The majority of patients (78%) were in the maintenance phase of therapy. 34 subjects received the HD TIV and 16 subjects received the SD TIV (mean age 7.8 vs. 9.3 years), with 11 subjects receiving 2 doses (9 in HD and 2 in SD groups). The only significant difference noted between the HD and SD TIV group was mean total CD19 count (29 vs. 56, p=0.027). There were no significant differences reported in local or systemic symptoms, except fatigue/malaise and headaches were reported more frequently in the SD TIV group (p=0.008 and p=0.03, respectively). No severe adverse events were attributed to vaccination. The immune response measured by a ≥ 4-fold rise in titers for each vaccine antigen were similar in both the HD and SD TIV groups after 1 or 2 vaccines, respectively (A/California: p=0.12, p=0.46; A/Perth: p=0.35, p=0.34; B/Brisbane: p=0.42, p=0.89). Please see refer to tables 1 and 2 for further immunogenicity results.

No differences were noted between the HD and SD TIV groups for solicited systemic and local reactions. The immune response appeared similar in both vaccine groups. A phase 3 trial is planned to determine the immunogenicity of HD versus SD TIV in the pediatric ALL population.

No relevant conflicts of interest to declare.