Therapy-related myeloid neoplasms - what have we learned so far?

Abstract

Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase II inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapy-related myeloid neoplasms would help developing risk-adapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment.

Keywords: Alkylating agents; Allogeneic hematopoietic stem cell transplantation; Ionizing radiation; Therapy-related acute myeloid leukemia; Therapy-related myelodysplastic syndromes; Therapy-related myeloid neoplasms; Topoisomerase II inhibitors.

Figure 1

Algorithmic approach to patients with therapy-related myeloid neoplasms. ¹Oken et al[109]; ²Sorror[110]; ³Litzow et al[68]. ECOG: Eastern Cooperative Oncology Group; APL: Acute promyelocytic leukemia; ATRA: All-trans retinoic acid; HiDAC: High-dose cytarabine; HCT-CI: Hematopoietic cell transplant-co-morbidity index.