Dr. Jean Sanders has treated children with cancer for 30 years, long enough to know a success story when she sees it. She also knows that it takes awhile to change people's minds about what works.
What works, Sanders announced in 2005, is treating infants with acute lymphoblastic leukemia (ALL) in first remission with total-body irradiation followed by a bone-marrow transplant. She and her Clinical Research Division team achieved an unprecedented success rate of 76 percent disease-free survival.
Sanders, director of the Hutchinson Center's pediatric stem-cell transplantation program, tracked the outcomes of 40 children diagnosed with ALL under the age of 12 months who were treated at the Center from 1982 to 2003. The children were then followed to determine any long-term effects of treatment on learning, growth and hormones.
Although cancer is rare in children, ALL — a cancer of the blood — is the most common malignancy in this population. During the past 35 years, the improvement in survival for children with ALL is one of the great oncology success stories. In the 1960s, less than 5 percent of children with ALL survived for more than five years. Cure rates in 2005 approach 80 percent for children between the ages of 1 and 9.
But the prognosis for infants with acute lymphoblastic leukemia is usually worse than for older children with the same diagnosis. For children with ALL under 1 year of age treated with chemotherapy — the most common approach at cancer centers today — the survival rate is only around 30 percent.
"They're tough to treat," Sanders said of this high-risk group. "These are fragile individuals. Transplanting individuals at either end of the age spectrum is challenging because they have unique medical reactions to the therapy."
"But we're experienced, and we pay attention to a lot of little details, so perhaps that made the difference in our results."
Radiation therapy for babies remains an unconventional approach because doctors fear the long-term repercussions on health. "The general opinion of most pediatric hematologists and oncologists is that radiation should not be used in infants because it will result in devastating, unacceptable late effects. That's not what we've observed," said Sanders, who is also a professor of pediatrics at the University of Washington School of Medicine.
The researchers found radiation therapy caused growth-rate and growth-hormone deficiencies, so the patients may need to take growth hormone. But according to Sanders, the babies proved resilient. "The fascinating thing about the infants is that, yes, they develop growth-hormone deficiency, but despite the fact that the blood tests tell you that they haven't got the ability to grow, they just go right ahead and grow anyway — which is perfectly fine," she said. "We'll take that any day of the week!"
Infants also experienced dental problems from the irradiation. The patients' permanent teeth frequently failed to develop as the children matured or were damaged in other ways.
High-dose irradiation of the brain can cause learning problems in children, but the lower amount of total-body irradiation used before a transplant has not caused similar problems. The Hutchinson Center clinicians found no long-term impact on intelligence when transplantation was used to treat infants with ALL. "Babies who are sick stop developing, and then when they get well, they begin developing and catch up," Sanders said. "By the time they get to be 5, they're going to school and they're learning and doing just what they ought to. We've tested some of the patients' IQs, and they're perfectly normal and they're in normal classes."
Sanders — who refers to her patients as "my babies" — is gratified by the study's results. "It's very satisfying for me to know that we're not causing irreparable damage, and we're saving children," she said. "It's so hard on parents to know their little babies — their pride and joy — are so sick. It's really a treasure to see them survive and grow up."