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5-year survival for pediatric ALL exceeds 90%
Study results show steady progress since the 1960s, but further improvements may be a challenge
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Results of a study of more than 20,000 children and adolescents with acute lymphoblastic leukemia showed that 5-year survival improved to 90.4% for those diagnosed from 2000 to 2005.
Five-year survival was 83.7% for patients diagnosed from 1990 to 1994.
Stephen Hunger, MD, director of the Center for Cancer and Blood Disorders at Children’s Hospital Colorado, said the results showed steady improvement since the early 1960s, when pediatric ALL was an incurable disease.
“Our goal is 100%. We don’t have final data yet, but I’m pretty sure from the numbers we do have that survival for patients treated from 2006 to 2010 is going to be a step up from the 2000-to-2005 data,” Hunger told HemOnc Today. “We are reaching the point of limited returns in terms of the approach of re-juggling the same set of drugs that we have, so a big focus now is to find specific molecular lesions that are fundamental to the cancer progress and target them with new agents.”
The Journal of Clinical Oncology published the results online March 12.
Timothy P. Cripe, MD, PhD, chief of the division of hematology/oncology and bone marrow transplantation at Nationwide Children’s Hospital in Columbus, Ohio, hailed these results but emphasized it will be difficult to continue to see improved survival.
“It was easy to find a difference between 100% mortality and 20% survival,” Cripe said. “To show a difference between, say, 93% to 95%, we need a lot of patients. Second, there is a limit with how well we can do with the current drugs, and we need other kinds of agents.
“Although this is all good news, these patients are not without problems when they’re cured,” Cripe said. “They have a lot of long-term side effects from treatment, so we certainly need to develop therapies that are as effective but less toxic.”
Hunger and colleagues reviewed data on 21,626 patients aged 0 to 22 years who were enrolled in 36 Children’s Oncology Group trials from 1990 to 2005. This population represents an estimated 55.8% of all diagnoses of ALL in patients aged younger than 20 years during the study period.
When researchers assessed survival in 5-year increments, they found steady improvement in survival. Survival improved significantly for all races, patients with B-cell or T-cell ALL, and those with standard- or high-risk disease. Relative reduction in 5-year risk for death between the 1990 to 1994 and 2000 to 2005 eras ranged from 30% to 50% in all non-infant subgroups.
Survival improved for all ages except infants aged younger than 1 year. Five-year cumulative incidence of death was stable from 1990 to 1994 and 2000 to 2005 (52.1% vs. 50.3%; P=.45), but the causes of death were different. The 5-year cumulative incidence of death after relapse or progression decreased from 43% from 1990 to 1994 to 27.2% from 2000 to 2005. Cumulative incidence of treatment-related death increased from 3.9% from 1990 to 1994 to 13.9% from 2000 to 2005.
“We’ve known for a long time that leukemia in infants tends to be a more aggressive, higher-risk form, so if you treat infants with the same regimen you use on older children, they do far worse,” Hunger said. “We’ve also known that infants were more vulnerable to side effects and complications, particularly infectious complications.”
Hunger said any increases in survival gained from stronger, more intensive treatment in infants were offset by deaths due to treatment-related adverse events.
Among all patients, 5-year cumulative incidence of death decreased from 16.35% from 1990 to 1994 to 9.6% from 2000 to 2005. Hunger and colleagues said a reduction in the 5-year cumulative incidence of death after relapse or progression from 12.83% from 1990 to 1994 to 7.22% from 2000 to 2005 was largely responsible for the overall decline in incidence of death.
Black patients, in particular, realized gains in survival relative to whites. The absolute difference in 5-year survival between blacks and whites declined from 11% from 1990 to 1994 to 3.3% from 2000 to 2005. Blacks have a higher incidence of T-cell ALL (17.7% vs. 9.5% of whites) and were more likely to have NCI high-risk features (44.5% vs. 32.9%), researchers said.
The absolute difference between blacks and whites in 5-year survival for patients with T-cell ALL decreased from 5% from 1990 to 1994 to 0.02% from 2000 to 2005. Similarly, the survival gap for children with NCI high-risk B-cell ALL decreased from 11.1% from 1990 to 1994 to 6.6% from 2000 to 2005.
The findings show the importance of research in curing disease, Hunger said. Without the contributions of thousands of patients and their parents over the decades, ALL still would be a death sentence.
“Research cures cancer,” Cripe said. “These results are a testament to the fact that studying disease in an organized, logical fashion produces results.” – by Jason Harris
Disclosure: Drs. Cripe and Hunger report no relevant financial disclosures.
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