These publications highlight recent findings in t-AML by researchers around the world:
[The World Health Organization (WHO) uses the term ‘therapy-relatedneoplasms’ (t-MN) to cover a spectrum of therapy-related disorders: Acute myeloid (t-AML); Myelodysplastic syndromes (t-MDS); and Myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN).]
t-AML Diagnosis and Incidence
- t-MDS/t-AML is a rare but lethal event in patients diagnosed with epithelial ovarian carcinoma. Vay et al. conducted an epidemiological analysis of patients diagnosed with epithelial ovarian carcinoma (EOC) to understand the risks of secondary leukemia following treatment. To date, no large series have been conducted to evaluate patient characteristics and outcomes associated with t-MDS/t-AML in these patients. Among 63,520 patients diagnosed with EOC in the National Therapy-related myeloid leukemia after treatment for epithelial ovarian carcinoma: An epidemiological analysis. Gynecol Oncol 123:456-60, 2011.) Institute’s Surveillance, Epidemiology and End Results (SEER) database, 199 secondary myeloid leukemia cases were identified (overall incidence rate of 0.17%) with a median survival of 3 months. Advanced age at ovarian cancer diagnosis and surgical treatment were significant risk factors. However, the incidence of t-MDS/t-AML has decreased since the use of platinum/taxane-based therapies became the standard of care. (Vay et al.
- The occurrence of t-MDS/t-AML is rare in children at high risk for acute lymphoblastic leukemia who have undergone treatment with dexrazoxane, a cardioprotectant drug. Anthracyclines, such as doxorubicin, are commonly used for the treatment of patients at high risk for The low incidence of secondary acute myelogenous leukemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukemia: A report from the Dana-Farber Cancer Institute ALL Consortium. Eur J Cancer 47: 1373-1379, 2011.) (ALL). However, acute and long-term cardiac toxicity is associated with their use. Vrooman et al. analyzed the incidence of t-MDS/t-AML among 553 children treated for high risk ALL with doxorubicin combined with dexrazoxane to prevent cardiotoxicity. The development of t-MDS/t-AML was extremely rare and observed in only 1 patient, suggesting that dexrazoxane is not associated with elevated risk for t-MDS/t-AML. (Vrooman et al.
Genetic Abnormalities in t-AML
- Dysfunctions in metabolic pathways are associated with t-MDS/t-AML development. Metabolomics, the characterization of small NMR-based metabolomic analysis of the molecular pathogenesis of therapy-related myelodysplasia/acute myeloid leukemia. J Proteome Res 10: 2873-2881, 2011.) metabolites generated from cellular processes, is emerging as an important discipline for discovering new biomarkers for disease. Cano et al. performed an NMR-based metabolomic analysis of peripheral blood samples from 12 patients prior to hematopoietic transplantation for Hodgkin or non-Hodgkin lymphoma. Of these patients, 6 subsequently developed t-MDS/t-AML. The analysis suggested that patients with t-MDS/t-AML had dysfunctions in alanine and aspartate metabolism, glyoxylate and dicarboxylate metabolism, the citrate acid cycle, and aminoacyl-t- biosynthesis. These dysfunctions may act as predisposing factors for the development of t-MDS/t-AML. (Cano et al.
t-AML Treatment and Outcomes
- Patient characteristics may predict the outcome of Allogeneic stem cell transplantation in therapy-related acute myeloid leukemia and myelodysplastic syndromes: impact of patient characteristics and timing of transplant. Leuk Lymphoma 53:96-102, 2011.) . Although allogeneic stem cell transplantation (alloSCT) may be considered as a treatment option for patients with t-MDS/t-AML, the rate of non-relapse mortality is high. Spina et al. conducted a retrospective study of 29 patients with t-MDS/t-AML treated with alloSCT to determine which patient characteristics may predict transplant outcomes. The 2-year overall, event-free survival, and non-relapse mortality rates observed were 37%, 34%, and 32% respectively. Patients with high-risk and disease at the time of transplant had lower rates of event-free survival, and patients who received greater than 2 lines of therapy for previous cancer had worse rates of non-relapse mortality. (Spina et al.