Attempting to Reduce the Chemotherapy Burden of Children With Acute Lymphocytic Leukemia

Reduced-intensity treatment was inferior to standard-intensity treatment in duration of disease-free survival (DFS) in pediatric patients with acute lymphocytic leukemia (ALL) who have standard-risk disease and are at a low risk for relapse, according to an analysis of the AIEOP-BFM-ALL 2000 trial. However, reduced-intensity treatment was associated with “dangerous” rates of relapse, according to lead author Martin Schrappe, MD, PhD, from the Department of General Pediatrics at the Christian-Albrechts University Kiel and University Medical Center Schleswig-Holstein in Kiel, Germany, who presented the results.

“These patients are at a very low risk for relapse, if any, so we wanted to see if it was possible to move away from the more toxic parts of therapy in the later stages of treatment, because relapses in low-risk leukemia occur late,” Dr. Schrappe told ASH Clinical News. “We found that it is dangerous to reduce treatment. It doesn’t cause ‘big’ trouble, but it causes significant trouble.”

In this trial, 1,164 pediatric patients with ALL (age range = 1-17 years) were randomized to standard protocol II (P-II; n=579) or reduced-intensity protocol III (P-III; n=584) to determine if it was possible to safely reduce treatment burden while maintaining efficacy and minimizing the risk of relapse. Patients included in the study had standard-risk disease and were minimal-residual disease (MRD)-negative at both days 33 and 78 after the start of induction therapy.

Both protocols consisted of dexamethasone, vincristine, doxorubicin, and cyclophosphamide; compared with P-II, P-III had a shorter cycle duration (29 vs. 49 days), a 30-percent lower dose of dexamethasone, and 50-percent lower doses of vincristine, doxorubicin, and cyclophosphamide.

After a median follow-up of 8.6 years, four-year DFS was 91.8 percent and 95.8 percent among patients who received reduced-intensity and standard-of-care treatment, respectively (p=0.04). However, the four-year cumulative incidence of relapse doubled among patients in the reduced-intensity P-III group, compared with the standard P-II group: 6.3 percent and 3.2 percent, respectively (p=0.09).

“Negative MRD does not mean that [a patient] is cured. If a patient has reached a plateau of cure (above 90%) be careful, because one cannot play around with this disease,” Dr. Schrappe concluded. “However, I can imagine that in the future, we will be able to identify subsets of patients through genetic screening who can be treated successfully with a different type of therapy.”


Reference

Schrappe M, Zimmermann M, Moricke A, et al. Reduced intensity delayed intensification in standard-risk patients defined by minimal residual disease in childhood acute lymphoblastic leukemia: results of an international randomized trial in 1164 patients (Trial AIEOP-BFM ALL 2000). Abstract #4. Presented at the 2016 ASH Annual Meeting, December 4, 2016; San Diego, California.

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