1. Infant Hepatitis B Vaccination and Childhood Leukemia Harold S. Margolis, MD Anthony Fiore, MD, MPH Division of Viral Hepatitis Centers for Disease Control and Prevention

2. The Studies No association Dockerty JD, Skegg DCG, Elwood JM, Herbison GP, Becroft DMO, Lewis ME. Infections, vaccinations, and the risk of childhood leukaemia. British Journal of Cancer 80(9): 1483-1489, 1999. Association – Ma XM, Does M, Buffler PA, Wiencke JK. Immunizations and risk of childhood leukemia: preliminary results from the Northern California Childhood Leukemia Study. Poster presentation: American Association for Cancer Research. San Francisco April 2002

3. ALL Incidence* and Hepatitis B Vaccine Coverage**, 1991-1998 *U.S. Residents, SEER Cancer Statistics, 1973-98 ALL Hepatitis B vaccine coverage **Vaccination coverage in 19-35 month old children, National Immunization Survey, 1998 data Leukemias

4. Northern California Childhood Leukemia Study (NCCLS) Incident cases of childhood leukemia (ages 0-14) ascertained from major medical centers 1995- 1999 Comparison California Cancer Registry indicated that 88% of newly diagnosed cases in area identified Detailed vaccination information obtained from immunization records

5. Study Population NCCLS cases Controls – Randomly selected from CA birth registry – Pair-matched on date of birth, gender, race, ethnicity, maternal county of residence at birth Eligibility – Reside in study area – <15 years of age at time of diagnosis or for control – One parent speak English or Spanish – No previous malignancy

6. Data Collection Parents provided copy of immunization record – if not available then physician record Exact date recorded for all vaccines Immunization data censored on dates of diagnosis

7. Analysis 167 case- birth control pairs –137 = ALL –133 ALL with immunization data Pearson’s Chi-square for demographic and socioeconomic characteristics Conditional logistic regression to estimate odds ratios as approximation of relative risk, adjusting for household income

8. Results Minimal discrepancy on race, ethnicity for cases and control Maternal education was comparable between groups Annual household income higher for controls

9. Results DTP, Polio, MMR not associated with overall leukemia or ALL 78% of cases and 79% of control received at least one dose of hepatitis B vaccine –Cases received more doses than controls –For each dose of HB vaccine the odds ratio was All leukemia = 1.20 (.89-1.62) ALL 1.31 (0.92-1.86) –Adjusting for birth order or daycare attendance did not change results

10. Hepatitis B Immunization and ALL, NCCLS HB Vaccine Number ALL-control pairs Adjusted OR 95% CI +/++/--/+-/- Ever9878200.95 (0.34, 2.67) > 3 doses75188322.92 (1.18, 7.19) 3 doses in 1 st year52195574.75 (1.67, 13.5) 3 doses in 1 st year and BW <3500 gm 148013incalculable

11. Issues Effect of birth dose vs later doses not analyzed Thimerosal-free vaccine not accounted for or analyzed (Combvax was in use during this time) Control group mainly of higher income - ? Less likely to be vaccinated Censoring of HB vaccine doses – prodromal period of ALL may mean increased physician visits and possible immunization at these visits Folate supplementation as possible confounder – has been shown to have weak association with ALL Future studies in progress – neighborhood controls