Hepatitis B and Leukaemia

Extract from report of GACVS meeting of 16-17 December 2002, published in the WHO Weekly Epidemiological Report on 24 January 2003

In June 2002,1 GACVS concluded that the suggestion of an association between hepatitis B vaccination at birth with thiomersal-containing vaccines and acute lymphoblastic leukaemia (based on an abstract presented at the April 2002 meeting of the American Association for Cancer Research) was not convincing and that the risk (if one exists at all) should be regarded as tentative at best and weighed against the proven benefits of hepatitis B immunization. The Committee resolved at the time that the matter should be kept under review and further investigated.

Four studies (in France, Germany (two case-control studies) and New Zealand) were identified that have considered the effect of immunization (and specifically of hepatitis B vaccination) on childhood leukaemia. None has supported the suggestion that there may be an increased risk of leukaemia following hepatitis B vaccination or any other routine infant vaccination. Additional research is currently being conducted by the United States Centers for Disease Control and Prevention and a retrospective review of data from the Vaccine Safety Datalink is ongoing. The Committee will continue to monitor the issue. On the basis of current evidence, GACVS does not recommend a change in current vaccination practices with hepatitis B vaccine.

1 See No. 50, 2002, p. 432.

Full report of GACVS meeting of 16-17 December 2002, published in the WHO Weekly Epidemiological Report on 24 January 2003

Extract from report of GACVS meeting of 20-21 June 2002, published in the WHO Weekly Epidemiological Record on 22 November 2002

An abstract presented at the April 2002 meeting of the American Association for Cancer Research reported an association between hepatitis B vaccine and acute lymphocytic leukaemia in 334 children in northern California. The investigators suggested that thiomersal may play a role since its effects were more likely to occur with repeated dosing. The authors pointed out that the results should be interpreted with caution. The research suggested a link only between thiomersal in the hepatitis B vaccine and leukaemia. Other childhood vaccines containing thiomersal were not implicated.

Ethyl mercury, as thiomersal, is excreted rapidly from the body, mostly disappearing within 5–6 days. Such brief exposure to minute amounts of mercury is unlikely to be a sufficient carcinogenic stimulus to trigger childhood leukaemia. There is no other documented association between mercury and any human cancer, leukaemia, lymphoma, or other malignant or pre-malignant disease. In animal studies, cancer has been associated only with metal carcinogens involving continual or repeated exposure.

GACVS concluded that the suggestion of an association between hepatitis B vaccine and acute lymphocytic leukaemia, from one source and based on small numbers, was not convincing. The purported association might equally be explained by the design of the study concerned, which did not preclude the chance of statistical bias; the result does not provide a convincing causal link. Furthermore, since an association cannot be disregarded on the basis of available evidence, the Committee resolved that the matter should be kept under review. At this stage, the risk, if any, must be regarded as tentative at best and weighed against the proven benefits of hepatitis B immunization.

It is nonetheless important that the association with hepatitis B vaccine be further investigated using appropriate and robust epidemiological methods. In that regard, additional research is being conducted by the US Centers for Disease Control and Prevention (CDC) using the Vaccine Safety Datalink.

GACVS will continue to review the evidence and any epidemiological data that may emerge from ongoing studies and evaluate the possibility of analysing other registries.

Full report of GACVS meeting of 20-21 June 2002, published in the WHO Weekly Epidemiological Record on 22 November 2002

Related links

Statement from the Global Advisory Committee on Vaccine Safety : The Global Advisory Committee on Vaccine Safety reassuring about suggested risk of childhood leukaemia following hepatitis B vaccination

August 2003, revised September 2007

An abstract (1) presented at the April 2002 meeting of the American Association for Cancer Research reported an association between hepatitis B vaccine and acute lymphocytic leukaemia in 334 children in northern California. The investigators suggested that thiomersal may play a role in the association as they found that the effect was more likely to occur with repeated dosing. The authors pointed out that the results should be interpreted with caution. The research suggested a link only between thiomersal in the hepatitis B vaccine and leukaemia. Other childhood vaccines containing thiomersal were not implicated.

Ethyl mercury, as thiomersal, is excreted rapidly from the body, mostly disappearing within 5-6 days. Such brief exposure to minute amounts of mercury is unlikely to be a sufficient carcinogenic stimulus to trigger childhood leukaemia. There is no other documented association between mercury and any human cancer, leukaemia, lymphoma or other malignant or pre-malignant disease. In animal studies cancer has only been associated with metal carcinogens involving continual or repeated exposure. Upon review of the evidence, the Global Advisory Committee on Vaccine Safety (GACVS) concluded that the suggestion of an association between hepatitis B vaccination and acute lymphoblastic leukaemia, from one study and based on small numbers, was not convincing and should be regarded as tentative at best and weighed against the proven benefits of hepatitis B immunization. The committee had resolved at that time that the issue should be kept under review and further investigated.

Four studies (in France (two case-control studies), Germany, and New Zealand) were identified that have considered the effect of immunization (and specifically of hepatitis B vaccination) on childhood leukaemia. None has supported the suggestion that there may be an increased risk of leukaemia following hepatitis B vaccination or any other routine infant vaccination. Preliminary results from additional research on this topic in the United States also do not show any association; they also suggest studies of this nature generally encounter and must overcome a number of methodological problems relating to differences in completeness of hepatitis B vaccination history between cases and controls. The most important of these is to verify that apparently incomplete vaccine series especially among controls are indeed incomplete and not the result of incomplete record keeping or data collection. This problem is especially important to consider for studies which do not find differences in ever/never exposure to a particular vaccine but find differences either in completion of the vaccine series overall or by a certain age. Furthermore the California researcher’s speculation that their findings might be due to thiomersal preservatives in hepatitis B vaccines is inconsistent with the fact that this vaccine represents only a very minor source of vaccine-associated mercury received by children in the U.S.

On the basis of current evidence, the committee has concluded that the evidence does not support the initial finding of an alleged association between hepatitis B immunization and childhood leukaemia and does not recommend a change in current vaccination practices with hepatitis B vaccine.

The GACVS will continue to review the evidence and any epidemiological data that might emerge from ongoing studies. On the basis of current evidence, GACVS does not recommend a change in current vaccination practices with hepatitis B vaccine.

The GACVS is a scientific advisory body established by WHO to provide a reliable and independent scientific assessment of vaccine safety issues in order to respond promptly, efficiently and with scientific rigour to such issues. Membership includes experts from around the world in the fields of epidemiology, statistics, paediatrics, internal medicine, pharmacology and toxicology, infectious diseases, public health, immunology and autoimmunity, drug regulation, and safety.

1. Ma X, Does M, Buffler PA, Wiencke JK. Hepatitis B vaccination and the risk of childhood leukaemia. Poster session abstract 3801, American Association for Cancer Research annual meeting, San Francisco, April 2002.

 

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