This article is more than 5 years old. Information may no longer be current.
Consolidation with arsenic trioxide effective for pediatric acute promyelocytic leukemia
Click Here to Manage Email Alerts
Children with acute promyelocytic leukemia achieved excellent survival rates with low risk for relapse following two cycles of arsenic trioxide consolidation and reduced doses of anthracyclines, according to results of a phase 3 historically controlled trial.
“The favorable results of this study incorporating arsenic trioxide consolidation with reduced anthracycline dose provide a new benchmark for outcome in pediatric acute promyelocytic leukemia (APL),” Matthew A. Kutny, MD, assistant professor of hematology and oncology at Children’s of Alabama, and colleagues wrote. “The use of arsenic trioxide allowed an approximate 40% decrease in cumulative anthracycline dosing without compromising survival in standard risk APL.”
APL, a subtype of acute myeloid leukemia, accounts for 6% of childhood AML cases and 1% of all childhood leukemias. It is most often diagnosed in children of Hispanic or Mediterranean descent aged 8 to 10 years.
Historically, treatment of pediatric APL has included high doses of anthracyclines, which carry risk for cardiac toxicity that increases with higher cumulative doses — 300 mg/m2 or more — and younger age at exposure. Anthracycline-based chemotherapy in combination with all-trans retinoic acid has improved survival for pediatric APL.
Researchers evaluated 101 newly diagnosed children (median age, 15 years; 56% female; 80% white) aged 2 to 21 years from the Children’s Oncology Group AAML0631 trial.
Kutny and colleagues used white blood cell count to stratify patients as standard risk (n = 66) or high risk (n = 35).
All patients received all-trans retinoic acid during induction, each consolidation course and maintenance. Patients received two cycles of arsenic trioxide (Trisenox, Cephalon) during first consolidation, plus additional consolidation courses — two for standard-risk patients and three for high-risk patients — that consisted of high-dose cytarabine and anthracycline. Patients also received 2 years of maintenance therapy with all-trans retinoic acid, oral methotrexate and mercaptopurine.
Safety and tolerability of arsenic trioxide consolidation and reduced doses of anthracyclines served as the primary endpoint. Median follow-up was 3 years.
Among all participants, 3-year OS was 94% and EFS was 91%. Standard-risk patients achieved higher 3-year OS (98% vs. 86%; P = .003) and EFS (95% vs. 83%; P = .03) than high-risk patients.
EFS for standard-risk patients appeared noninferior to that of patients in a previous trial — AIDA 0493 — which used a higher anthracycline dose and did not include arsenic trioxide consolidation.
Relapse risk from end of first consolidation after arsenic trioxide treatment was 4% at 3 years, with no significant difference between standard-risk and high-risk patients.
Limitations of the study included the nonrandomized designed — necessitated by the rarity of pediatric APL — and absence of a central review of end induction remission status.
“Treatment of pediatric APL with anthracyclines and all-trans retinoic acid has resulted in excellent outcomes, but in this young population intensive chemotherapy regimens may cause significant toxicity, including late cardiotoxicity,” Kutny and colleagues wrote. “Our trial demonstrates that chemotherapy with arsenic trioxide consolidation can result in a low relapse rate in both standard-risk and high-risk APL. Further research of supportive care and treatment strategies should be an objective of APL trials.” – by Chuck Gormley
Disclosures: The researchers report no relevant financial disclosures.
Click Here to Manage Email Alerts