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
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
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
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
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.