[Leukemias induced by anticancer chemotherapies]

Area of Science:

• Oncology
• Hematology
• Cancer Genomics
• Leukemogenesis

Context:

• Increasing incidence of treatment-related leukemia and myelodysplasia following cytotoxic chemotherapy.
• Cytotoxic agents, including alkylating agents and topoisomerase-II inhibitors, are associated with distinct secondary leukemias.
• These treatment-induced leukemias present significant theoretical and practical challenges in cancer treatment.

Purpose:

• To differentiate between alkylating agent-induced and topoisomerase-II inhibitor-induced leukemias based on clinical, hematological, and molecular characteristics.
• To highlight the prognostic differences and associated cytogenetic and molecular abnormalities for each leukemia type.
• To emphasize the need for updated data registers to assess and manage the risk of therapy-related leukemias.

Summary:

• Alkylating agent-induced leukemias typically manifest 5-6 years post-treatment, often preceded by myelodysplasia, and are characterized by chromosome 5/7 deletions with a poor prognosis.
• Topoisomerase-II inhibitor-induced leukemias occur 12-30 months post-treatment, present acutely (M4/M5 types), and are associated with balanced translocations, notably involving the MLL gene, with a less severe prognosis.
• Evaluating the risk of treatment-related leukemia is complex due to combination therapies, necessitating centralized data collection for myelodysplasia and leukemia.

Impact:

• Provides a framework for understanding the distinct mechanisms and clinical outcomes of different treatment-related leukemias.
• Informs the development of safer combination therapies by accounting for the risk of secondary leukemogenesis.
• Underscores the importance of robust data registries for monitoring and mitigating therapy-related hematological malignancies.