ASH: Long-term Childhood AML Survivors Do Well Overall

ORLANDO, Dec. 12 -- Young patients with acute myeloid leukemia are not only surviving but doing well in adult life, albeit with an increased risk for secondary cancers or heart disease, show data from the Childhood Cancer Survivor Study.

"Among five-year survivors of AML, long term survival is quite good, and generally over 90%," said Daniel A. Mulrooney, M.D., of the University of Minnesota of the American Society of Hematology meeting here.

But late recurrences and the medical late effects of therapy, such as second cancers and cardiovascular symptoms, warrant long-term follow-up, said Dr. Mulrooney.

The Childhood Cancer Survivor Study is the largest and longest prospective study of the consequences of cancer therapy. Investigators using data from the study have previously reported that long-time survivors of childhood leukemia and brain tumors, particularly those given cranial radiotherapy, are at a significantly greater risk for a stroke later in life compared with siblings, researchers here have found.

Late stroke rates among more than 4,800 leukemia survivors and more than 1,800 brain tumor survivors, compared with non-diseased siblings, showed that leukemia survivors had a nearly sevenfold relative risk for stroke, and brain tumor survivors had a nearly 30-fold risk.

Other studies using the data have shown that childhood cancer survivors of the 1970s and 1980s were more than three times as likely as their siblings to have a chronic health condition and more than eight times as likely to have a severe or life-threatening condition in the next five to 30 years.

In the current take on the data, Dr. Mulrooney and colleagues focused on both the late medical and social effects of aggressive therapy on those patients who as children or young adults were treated for acute myeloid leukemia.

They looked at a cohort of 275 five-year survivors who had been diagnosed with cancer at age 21 or younger from 1970 through 1986. The study excluded those patients who survived a blood or bone marrow transplant.

The survivors were compared to a control group of 3,899 siblings, and the data were age and gender adjusted.

The survivors, 55% female, were on average seven years old at diagnosis, and 28 years old at the most recent follow-up. The average follow-up was 22.6 years.

In all, 56% of the patients had received chemotherapy alone, and 34% had received chemoradiation.

The investigators found that among this group of five-year survivors, overall survival was 97% (95% confidence interval, 94-98%) at 10 years, and 94% (95% CI, 92-97%) at 20 years.

There were six patients who had eight AML recurrences at a mean of 11.1 years (range 5.6-16.6 years) from diagnosis. Two of these patients died from relapse, one from congestive heart failure, and one from a myocardial infarction.

The all-cause standardized mortality ratio was 4.7 (95% CI, 2.8-7.5). The cumulative incidence of recurrent AML at 10 years was 1.8% (95% CI, 0.2-3.4%) and at 20 years was 3.7% (95% CI, 1.4-5.9%).

Eight survivors reported 10 subsequent malignant neoplasms: five breast cancers, three central nervous system tumors, one ovarian tumor, and one salivary gland tumor. These secondary cancers occurred a mean of 18.7 years (range 9.2-26.4 years) from diagnosis. Three of the patients with second malignant neoplasms had a history of radiotherapy exposure. The cumulative incidence of the second cancers was 1.6% (95% CI, 0.02-3.3%) with a standardized incidence ratio of 3.2 (95% CI ,1.4-6.0).

Other effects included five cases of congestive heart failures and one myocardial infarction, which occurred a mean of 16.4 yrs (range 12.8-18.4 years) after diagnosis. The 20-year cumulative incidence was 2.4% (95% CI 0.5-4.4%).

"Interestingly, in this study we looked at social late effects, particularly marriage, education , and employment rates, and although they may be lower than expected compared with a sibling comparison group, they did not appear significantly different when we compared them to the general U.S. population," Dr. Mulrooney said.

In the group of survivors age 25 and older, 59% were married, a rate similar to that in the general population, but lower than that among the sibling comparison group (69%, P