Mitoxantrone in refractory acute leukemia in children: a phase I study

Area of Science:

• Pediatric Oncology
• Hematology
• Pharmacology

Background:

• Leukemia is a significant pediatric cancer.
• Conventional therapies often fail in relapsed or refractory cases.
• Anthracycline resistance is a challenge in leukemia treatment.

Purpose of the Study:

• To evaluate the efficacy and toxicity of mitoxantrone in pediatric patients with refractory acute leukemias.
• To determine optimal dosing for induction therapy.

Main Methods:

• A 5-day course of mitoxantrone was administered to pediatric patients with acute non-lymphocytic leukemia (ANLL) and acute lymphocytic leukemia (ALL).
• Two dose levels were tested: 6 mg/m²/day and 8 mg/m²/day.
• Patients had leukemia resistant to conventional therapy, many with prior anthracycline exposure.

Main Results:

• At 6 mg/m²/day, two ANLL patients achieved partial remission (PR).
• At 8 mg/m²/day, four patients achieved complete remission (CR) (one ANLL, three ALL), and one ANLL patient achieved PR.
• Toxicity was dose-limiting at 8 mg/m²/day, with mucositis and nausea observed, while 6 mg/m²/day showed no dose-limiting toxicity.

Conclusions:

• Mitoxantrone demonstrates activity in pediatric refractory leukemias.
• The 6 mg/m²/day dose appears better tolerated, while the 8 mg/m²/day dose shows higher response rates but increased toxicity.
• Further investigation into mitoxantrone's role in pediatric leukemia is warranted.