Characterization of therapy-related acute myeloid leukemia: increasing incidence and prognostic implications

Abstract

Studies of therapy-related AML (t-AML) are usually performed in selected cohorts and reliable incidence rates are lacking. In this study, we characterized, defined the incidence over time and studied prognostic implications in all t-AML patients diagnosed in Sweden between 1997 and 2015. Data were retrieved from nationwide population-based registries. In total, 6779 AML patients were included in the study, of which 686 (10%) had t-AML. The median age for t-AML was 71 years and 392 (57%) patients were females. During the study period, the incidence of t-AML almost doubled with a yearly increase in t-AML of 4.5% (CI 2.8% - 6.2%), which contributed significantly to the general increase in AML incidence over the study period. t-AML solidly constituted over 10% of all AML cases during the later study period. Primary diagnoses with the largest increase in incidence and decrease in mortality rate during the study period (i.e. breast and prostate cancer) contributed significantly to the increased incidence of t-AML. In multivariable analysis, t-AML was associated with poorer outcome in cytogenetically intermediate and adverse risk but t-AML had no significant impact on outcome in favorable risk AML, including core binding leukemias, APL and AML with mutated NPM1 without FLT3-ITD. We conclude that t-AML displays a strong increase in incidence over time and that t-AML constitutes a successively larger proportion of the AML patients. Furthermore, we conclude that t-AML confer a poor prognosis in cytogenetically intermediate and adverse risk, but not in favorable risk AML.

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

“…105,106 The percentage of t-AML continues to rise due, at least in part, to the increasing numbers of cancer survivors at risk, 107 especially for breast and prostate cancer. 106 Notably, chemotherapy and radiotherapy treatment for a solid cancer is associated with an increased risk of AML up to 10-fold 107 and 2.5-fold, 108 respectively. The mechanisms through which chemo-and/or radiation therapy cause AML has been partially clarified.…”

“…Excluded from this category are progression of myeloproliferative neoplasms and evolution of primary MDS or MDS/MPN to AML 1 . About 5%–10% of all AML cases are regarded to be therapy‐related 105,106 . The percentage of t‐AML continues to rise due, at least in part, to the increasing numbers of cancer survivors at risk, 107 especially for breast and prostate cancer 106 .…”

“…About 5%–10% of all AML cases are regarded to be therapy‐related 105,106 . The percentage of t‐AML continues to rise due, at least in part, to the increasing numbers of cancer survivors at risk, 107 especially for breast and prostate cancer 106 . Notably, chemotherapy and radiotherapy treatment for a solid cancer is associated with an increased risk of AML up to 10‐fold 107 and 2.5‐fold, 108 respectively.…”

Progress toward Better Treatment of Therapy-Related AML

“…According to the 2017 World Health Organization (WHO) classification system for tumors of hematopoietic and lymphoid tissues, therapy-related myeloid neoplasms include cases of acute myeloid leukemia (t-AML), myelodysplastic syndromes (t-MDS), and myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN), which arise as a complication of cytotoxic chemotherapy and/or radiation therapy administered for a prior neoplastic or non-neoplastic disorder [ 1 ]. Epidemiologic evidence shows that the incidence of t-AML has greatly increased during the past three decades as a result of better (but also mutagenic) cancer treatments and the increased survival of cancer patients [ 2 ].…”

“…In rare cases, t-AML may follow high-dose chemotherapy in the context of treatment of a non-myeloid disorder, e.g., autologous stem-cell transplantation for Crohn’s disease or multiple sclerosis. AML occurring after treatment for non-neoplastic disorders accounts for 5–20% of all cases of t-AML [ 2 ].…”