Haemophilus influenzae type b vaccination and risk of childhood leukemia in a vaccine trial in finland

Abstract

PURPOSE: To compare the incidence of childhood leukemia among children who received multiple early vaccine doses versus a single late dose in the context of a clinical trial in Finland during 1986 and 1987.METHODS: The trial was offered to the parents of all 114,000 children born in Finland between October 1, 1985 and August 31, 1987; 98% of the eligible children were enrolled. The vaccine consisted of heat-sized capsular polysaccharide of Haemophilus influenzae type b (Hib) coupled to diptheria toxoid (PRP-D). Children with odd birth dates received four doses of the vaccine at the ages of 3, 4, 6, and 14 months; children with even birth dates received only one dose, at the age of 24 months. The numbers of boys and girls with even and odd birth dates during the window of eligibility who remained alive during the follow-up period were obtained from the Finnish Population Registry. Numbers of leukemia cases diagnosed through 1996 among children with even and odd birth dates during the window of eligibility were obtained from the Finnish Cancer Registry. Poisson regression analysis of leukaemia incidence rates was conducted using the number of cases as the outcome variable and the natural logarithm of number of children at risk as an offset term. For comparison of the early and late vaccination groups, a binary variable based on odd or even date of birth was used.RESULTS: Among the 114,000 subjects, a total of 77 cases of childhood leukaemia were diagnosed: 33 in the early-vaccination group and 44 in the late-vaccination group. The incidence of childhood leukaemia was lower in the early-vaccination group (relative risk 0.72, 95% confidence interval 0.46–1.13) than in the late-vaccination group, but the difference did not reach statistical significance.CONCLUSIONS: Our results suggest that early vaccination against Hib may reduce the incidence of childhood leukaemia, but confirmatory studies are needed.