ALL patients risk growing up short

Acute lymphoblastic leukemia is the most common childhood cancer in developed countries, and researchers are beginning to understand the long-term implications of the disease. In the 1970s and 1980s, physicians relied on cranial radiation and chemotherapy to combat ALL. Now that survivors are full-grown, side effects of the treatment are beginning to surface.

In a recent paper published in the Journal of Pediatrics, Center researchers report that survivors of childhood ALL have an increased chance of being significantly shorter as adults compared with siblings. The study was based on the Childhood Cancer Survivor Study, which involved the Hutchinson Center and 26 other institutions and analyzed nearly 10,400 adults who were diagnosed between 1970 and 1986. Within that group, almost half were ALL survivors, so the data provided the largest and most powerful results to date.

"This study was very large, which allowed us to tease apart the effects of high-dose cranial radiation versus low-dose cranial radiation to see if the lower doses were associated with the same side effects," said Dr. Eric Chow of the Clinical Research Division and lead author of the paper. "There is a smaller subset of patients that didn't get any cranial radiation, only chemotherapy, and we wanted to know if those patients were at some risk or not."

The team's hypothesis — that dosage corresponded with risks of shorter stature — proved correct, but Chow said one of the most interesting finds was among the subset of chemotherapy-only patients.

"The patients who received only chemotherapy were also at an increased risk of short stature, but less than patients who had cranial radiation. Unfortunately, we weren't able to see from the data what component of chemotherapy might be associated with that risk or whether shorter stature reflects chronic illness and, for example, poorer nutrition," Chow said.

Because patients today rarely receive cranial radiation, researchers are working to better understand the subset of chemotherapy patients. "It raised some interesting questions for current patients. Decreased height is really just the tip of the iceberg. Height in some ways is a cosmetic side effect, but there are a lot of other risks like obesity, early death from cardiovascular disease, and developing a second cancer," Chow said. "There's a growing appreciation of the long-term negative effects of treatment, a lot of which won't be seen until these kids are middle-aged. So we're working to understand what aspects of treatment are causing these effects."

Chow's work is funded by a pediatric-oncology research fellowship-training grant by the National Institutes of Health and the National Cancer Institute.