Treatment Does Not Delay Physical Maturity in Girls Who Survive Leukemia

National Institute of Child Health and Human DevelopmentFOR IMMEDIATE RELEASE, Wednesday, November 19, 1997Robert Bock

Survivors of childhood acute lymphoblastic leukemia are not likely to undergo their first menstruation any later than other girls, according to a study by researchers at the National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), and other institutions.

The Leukemia Follow-Up Study, conducted by the NICHD, NCI and the Children's Cancer Group, appears in the October issue of The Journal of Pediatrics, (mailed in Mid November).

Previous studies have indicated that leukemia treatment might delay physical maturation or prevent menstruation entirely in young girls who had survived leukemia, explained the paper's first author, James L. Mills, MD, Chief of NICHD's Pediatric Epidemiology Section.

"The results of our study are generally reassuring," Dr. Mills said. "We can be confident of our findings, as we had more patients to observe than did many of the earlier studies and a longer time to follow them up."

Leukemia is a cancer of the infection-fighting white blood cells. Acute leukemia progresses in a short time, compared to other forms of the disease. The disease is the most common form of childhood leukemia, representing about 85 percent of all childhood leukemia cases. In the U.S., leukemia strikes 4.2 white children per 100,000 each year, and 2.4 black children per 100,000. More than 70 percent of acute lymphoblastic leukemia (ALL) patients survive the disease. Treatment for ALL consists of anticancer drugs (chemotherapy), and sometimes, radiation.

For their study, the researchers recruited 188 survivors of a large treatment study of childhood leukemia. All the young women who took part in the study were at least 18 years of age. The women were asked whether they had ever had a menstrual period, at what age they had experienced menarche (the first period), and whether they had to take medication to start or continue their periods. The responses of each patient were compared to the responses of a woman who served as a control--usually, the sister of the leukemia patient.

Of the 188 survivors, 172 had experienced menarche within the normal age range. Only 4 had abnormally early menarche (before age 10), and 12 had abnormally late (after age 16) or absent menarche. In fact, the age of menarche in the treatment group did not differ signficantly from that of the control group.

The researchers noted that time of menarche seemed to be influenced by the form of treatment the survivors had received. For example, leukemia survivors who were diagnosed before the age of 8 and who had received 1800 centiGrays (cGy) of radiation to the head were more likely to experience menarche too early, compared to the women in the control group. In contrast, patients who received 2400 cGy of radiation to the spine were more likely to experience menarche too late, compared to the control group.

Treatment with the anticancer drugs known as alkylating agents was not found to delay menarche.

The researchers noted that therapy for ALL has changed slightly since the women in the study originally received their treatment. Instead of radiation to the head, children are more likely to be given the anticancer drug methotrexate in the fluid that bathes the brain and spinal cord. However, the doses of radiation currently given to patients for whom leukemia has entered the brain or spinal cord, and to those whose leukemia has relapsed, are similar to the radiation doses the women in the study received.

"In conclusion, this study shows that the vast majority of long-term female survivors of ALL will reach menarche at the normal time without any medical intervention," the authors wrote.

They added, however, that girls who receive 1800 cGy of radiation to the head at an early age are at increased risk for premature menarche and those who receive 2400 cGy to the spine are at risk for delayed menarche, and so require careful monitoring.

The National Cancer Institute established an Office of Cancer Survivorship in 1996 to provide support and a focus for research and other activities dealing with cancer survivors. Twenty supplements to existing grants and cooperative agreeements have already been awarded, and $3 million a year for 5 years has been committed for studies of problems affecting long-term cancer survivors. The first awards will be given in mid-1998.

Authors of the study were James L. Mills, MD, the National Institute of Child Health and Human Development; Thomas R. Fears, the National Cancer Institute; Leslie L. Robison, University of Minnesota; H. Stacy Nicholson, and Julianne Byrne, Children's National Medical Center; and Charles A. Sklar, Memorial Sloan Kettering Cancer Center.