Human growth hormone treatment-leukemia link reported.

Human growth hormone treatment-leukemia link reported

Short-statured youngsters receiving human growth hormone treatments appear at increased risk of developing leukemia, preliminary data suggest. However, it is unclear whether treatment with hGH actually causes the cancer, a new report concludes, and the risk associated with the treatment is too small to warrant withholding the drug.

The hormone -- purified from human pituitary extracts or mass-produced by genetically engineered microorganisms -- is the only effective treatment for dwarfism caused by insufficient pituitary gland activity in the brain.

The new findings suggest that -- compared to their age-matched, normal peers -- growth-hormone-treated children have a two-fold risk of developing leukemia within four years after the completion of treatment. The findings are based on data presented by an international team of experts attending a two-day workshop in Bethesda, Md., last week. Recent reports of leukemia in five Japanese children treated with the hormone prompted the workshop.

"My sense of the risk is that this is minuscule compared to [the risk of] crossing town to go to the doctor to get checked," said panelist Louis Underwood at a briefing following the workshop. Underwood, a pediatric endocrinologist at the University of North Carolina School of Medicine in Chapel Hill, said he hopes the panel's conclusions "might counteract the fright" from earlier European reports suggesting the risk of hGH treatment is more substantial. Nevertheless, he says, many questions about the links between hGH treatment and leukemia remain unanswered, and further epidemiological studies need to be done.

The U.S. Public Health Service is currently gathering data from every U.S. patient who has ever taken the drug, according to Judith Fradkin, chief of the Endocrine and Metabolic Diseases Program Branch of the National Institute of Diabetes, Digestive and Kidney Diseases in Bethesda. That study is expected to be completed in 6 to 8 months. Of the 11 leukemia cases so far associated with hGH treatment worldwide, 3 occurred in the U.S. However, Fradkin notes, the data are complicated because all 3 of those patients also received head irradiation for brain tumors. Scientists are uncertain whether head irradiation increases leukemia risk.

According to the panel report, the risk of leukemia among hGH-treated patients is 1 per 21,000 patient-years, compared to 1 per 42,000 patient-years for untreated, normal individuals in the same age range. No data are available on leukemia rates among untreated, hypopituitary patients, leaving open the possibility the leukemia link may result from an underlying genetic condition associated with hypopituitarism rather than the hGH treatment. Alternately, the panelists say, either hGH itself or a contaminant in its preparation may be causing the additional leukemias.

Growth hormone derived from human pituitary extract has not been approved for treatment in the United States since April 1985, when its use led to several deaths from Creutzfeldt-Jakob disease, a rare, infectious neurological condition. The extract is still sold in Europe and Japan, but is now purified by a different process than was used in the U.S.

Recombinant hGH, currently sold in the U.S. and elsewhere, is made by Genentech of South San Francisco and Eli Lilly of Indianapolis, Ind. The new data show no correlation between leukemia rates and different sources of hGH, but were again complicated because some leukemia patients received both pituitary-derived and recombinant versions.

For now, concludes panelist Delbert Fisher of the University of California at Los Angeles School of Medicine, patients should be told that if there is an increase in risk from hGH treatment, it is small. Because no alternative exists, he says, it would be "inappropriate and unwise" to withhold treatment from needy patients.