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Recombinant interferon alfa given before and in combination with standard chemotherapy in children with acute
J Ochs1, M L Brecher, D Mahoney
1St Jude Children's Research Hospital, Memphis, TN.
Insights
High-dose recombinant interferon alfa (rIFN-alpha) showed modest effects in children with relapsed acute lymphoblastic leukemia (ALL). However, pulsed rIFN-alpha during continuation therapy did not impede standard chemotherapy intensity.
Area of Science:
- Pediatric Oncology
- Hematology
- Immunotherapy
Background:
- Acute lymphoblastic leukemia (ALL) relapse in children presents significant treatment challenges.
- Recombinant interferon alfa (rIFN-alpha) has been explored for its antileukemic properties.
Purpose of the Study:
- To evaluate the efficacy and toxicity of high-dose rIFN-alpha as initial treatment for pediatric ALL relapse.
- To assess the safety and impact of pulsed rIFN-alpha during continuation chemotherapy.
Main Methods:
- 31 children with first on-therapy marrow relapse of ALL received rIFN-alpha.
- Initial treatment involved intravenous rIFN-alpha followed by standard reinduction and pulsed subcutaneous rIFN-alpha during continuation therapy.
- Toxicity and antileukemic effects were monitored.
Main Results:
- Initial rIFN-alpha resulted in partial remissions or blast reduction in 9/31 patients; 2 had progressive disease.
- 74% of children achieved remission with subsequent standard chemotherapy.
- Pulsed rIFN-alpha during continuation therapy was generally well-tolerated and did not compromise standard chemotherapy intensity.
Conclusions:
- High-dose rIFN-alpha monotherapy has a modest antileukemic effect in relapsed pediatric ALL.
- Pulsed rIFN-alpha can be integrated into continuation therapy without compromising standard chemotherapy.
- Further research may explore optimized combination strategies for relapsed ALL.
Abstract:
Recombinant interferon alfa (rIFN-alpha) 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 x 10 days) before standard four-drug reinduction and during multiagent continuation therapy (30 megaunits/m2 subcutaneously x 3 consecutive days every 3 weeks). After 10 days of rIFN-alpha, there were two partial remissions (PRs); seven additional patients had either greater than or equal to 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 teniposide (VM-26) and cytarabine (ara-C) consolidation due to toxicity. Continuation therapy including rIFN-alpha pulse was well tolerated in the remaining children; only one patient required rIFN-alpha dosage reduction (for CNS toxicity). rIFN-alpha 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-alpha alone had a modest antileukemic effect. In contrast to the clinical experience with combined rIFN-alpha and chemotherapy in adults, rIFN-alpha given in a pulse-like manner throughout continuation therapy did not compromise the intensity of the standard chemotherapy regimen.