Recombinant interferon alfa given before and in combination with standard chemotherapy in children with acute lymphoblastic leukemia in first marrow relapse: A Pediatric Oncology Group Pilot Study

Recombinant Interferon alfa (rIFN-α) was given to 31 children with acute lymphoblastic leukemia (ALL) in first on-therapy marrow relapse as the sole treatment (30 megaunits/m²/d intravenously × 10 days) before standard four-drug reinduction and during multiagent continuation therapy (30 megaunits/m² subcutaneously × 3 consecutive days every 3 weeks). After 10 days of rIFN-α, there were two partial remissions (PRs); seven additional patients had either ≥ 25% reduction in the percentage of marrow blast cells or hypoplastic marrow. Two patients had progressive disease with an increase in leukocyte counts. All patients experienced influenza-like symptoms, and there were isolated instances of severe abdominal pain and personality change. Dose-limiting toxicity comprised grade III/IV transaminase elevation (two patients) and syncope with personality change (one patient). Twenty-three of 31 children (74%) subsequently achieved marrow remission using standard agents. One patient was taken off study during tenipo-side (VM-26) and cytarabine (ara-C) consolidation due to toxicity. Continuation therapy including rIFN-α pulse was well tolerated in the remaining children; only one patient required rIFN-α dosage reduction (for CNS toxicity). rIFN-α toxicity did not necessitate reductions in doses of standard chemotherapy agents or significant delays in therapy. Five patients remain in remission at 26 + to 36+ months; 13 patients relapsed in marrow, one in the meninges (7 months), and one in meninges, mediastinum, and lymph nodes (2 months). Two children were removed from study for marrow transplant. In summary, high-dose rIFN-α alone had a modest antileukemic effect. In contrast to the clinical experience with combined rIFN-α and chemotherapy in adults, rIFN-α given in a pulse-like manner through-out continuation therapy did not compromise the intensity of the standard chemotherapy regimen.