Young adults with acute lymphoblastic leukemia (ALL) benefit from therapies developed for children

Results from a large, prospective clinical trial add to mounting evidence that patients with acute lymphoblastic leukemia (ALL) who are adolescent and young adult (defined as ages 16 to 39 years) tend to fare better when treated with high-intensity pediatric protocols than previous patients who were treated with standard adult regimens.

The intergroup trial, presented at the 56th annual meeting of the American Society of Hematology in San Francisco, California, enrolled 296 adolescent and young adult patients with ALL. All participants were treated by adult hematologists-oncologists with a pediatric protocol, including four intensive courses of chemotherapy.

After 2 years of follow up, 78% of the patients achieved overall survival and 66% of patients maintained event-free survival, which is time after treatment without recurrence, progression, or death.

Wendy Stock, MD, professor of medicine at the University of Chicago and the study's main author, said the 66% event-free survival rate was a significant improvement over previous studies for this age range, which showed an event-free survival rate of 34%.

"We showed that adolescents and young adults could tolerate an intensive pediatric regimen. The protocol resulted in low treatment-related mortality, less than 2%, and improved both disease-free and overall survival," Stock said. "Our results are important because most adolescent and young adult patients with ALL are still treated with lower-intensity adult regimens and are not enrolled on clinical trials."

Still, she cautioned that these findings need to be confirmed with longer follow-up.

The evidence for better results from higher-intensity therapy dates back to 2000, when Stock and pediatric oncologist James Nachman, MD, also from University of Chicago, examined ALL trials conducted over the last 10 years by two cancer cooperative groups: one pediatric and one adult.

They found a stunning difference. Patients with ALL ages 16 to 21 years who enrolled in pediatric trials had a progression-free survival rate of 68%, whereas patients with ALL ages 16 to 21 years who enrolled in the adult trials had a progression-free survival rate of 34%, approximately the same as patients ages 22 to 39 years. Retrospective studies from France, the United Kingdom, and the Netherlands had similar results. These data led the US cooperative groups to perform the prospective C10403 study.

Biological disease factors other than the treatment also play a role, the researchers point out. High initial white blood cell counts, or the presence of minimal residual disease after the first month of therapy, were linked to poor outcomes. Two-year event-free survival for patients with a leukemia-specific molecular genetic profile indicating aggressive disease was 52% compared to 81% for those who lacked the genetic alteration.

"With these new insights, we can now focus future clinical trial research to build upon the C10403 regimen and evaluate new targeted agents to eradicate minimal residual disease in young adults with ALL and further improve their long-term survival," Stock said.

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