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Response to alpha-interferon in children with Philadelphia chromosome-positive chronic myelocytic leukemia
L W Dow1, S C Raimondi, S J Culbert
1Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Insights
Alpha-interferon (alpha-IFN) therapy showed therapeutic efficacy in children with Philadelphia chromosome-positive chronic myelocytic leukemia (Ph+ CML). Some patients achieved hematologic response and reduced Ph+ cells, indicating potential for further clinical testing.
Area of Science:
- Pediatric Hematology
- Oncology
- Immunotherapy
Background:
- Philadelphia chromosome-positive chronic myelocytic leukemia (Ph+ CML) is a rare hematologic malignancy in children.
- Previous treatments for Ph+ CML in pediatric patients often involved cytoreductive agents.
- The role of alpha-interferon (alpha-IFN) in pediatric Ph+ CML management required further investigation.
Purpose of the Study:
- To evaluate the therapeutic efficacy and toxicity of alpha-interferon (alpha-IFN) in pediatric patients with Ph+ CML.
- To assess the impact of alpha-IFN on hematologic response and Philadelphia chromosome-positive (Ph+) cell reduction.
- To identify adverse events associated with alpha-IFN treatment in this population.
Main Methods:
- A cohort of 15 children (6-20 years) with Ph+ CML received intramuscular alpha-IFN therapy.
- Patients had prior cytoreductive therapy (hydroxyurea and/or busulfan).
- Dosing started at 5 x 10(6) U/m2/d, escalated to 10 x 10(6) U/m2/d if needed.
Main Results:
- Ten out of 15 children achieved a hematologic response.
- Nine patients showed a reduction in Ph+ marrow cells, with four achieving undetectable Ph+ cells.
- Common side effects included fever and malaise; serious adverse events were seizures and aseptic necrosis.
Conclusions:
- Alpha-interferon (alpha-IFN) demonstrates therapeutic efficacy in stabilizing chronic phase Ph+ CML in some children.
- The treatment is generally well-tolerated at doses of 2.5-5 x 10(6) U/m2/d.
- Combination therapy with alpha-IFN and cytoreductive agents warrants further clinical investigation for pediatric Ph+ CML.
Abstract:
The therapeutic efficacy and toxicity of alpha-interferon (alpha-IFN) (Roferon, Hoffmann-La Roche, Inc., Nutley, NJ) were determined in 15 children (age range, 6 to 20 years) with Philadelphia chromosome-positive chronic myelocytic leukemia (Ph+ CML). All patients had received cytoreductive therapy with either hydroxyurea (n = 13) or busulfan (n = 1) or both (n = 1) for 6 weeks to 46 months (median, 7 months) before beginning alpha-IFN therapy at a dose of 5 x 10(6) U/m2/d intramuscularly. This dose was escalated to 10 x 10(6) U/m2/d if leukemia was inadequately controlled. Ten children had a hematologic response, with nine showing a reduction in the percentage of Ph+ marrow cells, including four who had no detectable Ph+ cells in marrow samples collected 48 to 204 weeks after the initiation of therapy. Two of 15 patients remain free of Ph+ cells. Therapy was discontinued before week 104 in ten patients because of the following: (1) early hematologic responses without a decrease in Ph+ cells (three patients); (2) early resistant disease (one patient); (3) blast crisis (one patient); (4) progressive disease (two patients); (5) seizure attributed to high-dose alpha-IFN (one patient); or (6) an inadequate trial of alpha-IFN caused by aseptic necrosis or poor compliance (two patients). The most common side effects were mild and have included fever, malaise, headache, myalgias, and pain at the injection site. Adverse events causing interruption of therapy were seizures, aseptic necrosis, and myelofibrosis. alpha-IFN stabilizes the chronic phase of Ph+ CML in some children, is adequately tolerated when administered at a dose of 2.5 to 5 x 10(6) U/m2/d intramuscularly, and results in a significant decrease in the proportion of Ph+ metaphases in some patients. alpha-IFN in combination with an effective cytoreductive agent or agents appears worthy of further clinical testing in this disease.