Is it possible to cure childhood acute myeloid leukaemia without significant cardiotoxicity?

Abstract

Since cardiotoxicity is a life threatening late effect, a reduction of cardiotoxicity in the treatment of acute myeloid leukaemia (AML) is essential. This review is a compilation of the current knowledge about cardiotoxicity after AML treatment and of how future directions in treatment may affect its incidence. A total of six studies concerning AML and cardiotoxicity were identified. The incidence of late subclinical cardiotoxicity varied between 1·3 and 15·3%, and late clinical cardiotoxicity varied between 1·3 and 9·3%. Cumulative dose of anthracyclines (ACs) and history of relapse were the most common risk factors identified. No conclusions could be drawn about new, potentially less toxic ACs. Differences in treatment data and variations in study populations made comparisons uncertain. The echocardiographic techniques used in the majority of the studies are inferior to more modern echocardiographic methods. This decreases reproducibility and may increase the risk of overestimation of cardiotoxicity. In summary, AML cannot be cured today without ACs. However, some ACs may cause less cardiotoxicity than others. Furthermore there is currently no consensus on equipotent doses of ACs and risk factors for cardiotoxicity. Further research including randomized trials is needed to evaluate whether or not the potentially less cardiotoxic agents fulfil their promise.

RNAi prodrugs decrease elevated mRNA levels of Polo‐like kinase 1 in ex vivo cultured primary cells from pediatric acute myeloid leukemia patients

“…Allogeneic stem cell transplantation is one of the approaches that is used in AML when other therapy options are exhausted 6 . Moreover, pediatric patients who recover from AML are prone to develop long‐term side effects such as growth delay, second cancers, cardiac toxicity, and cognitive problems 7‐10 . Thus, a novel treatment, effective enough to eliminate cancer cells with minimal influence on normal bodily functions, is needed, especially for pediatric AML patients.…”

“…from AML are prone to develop long-term side effects such as growth delay, second cancers, cardiac toxicity, and cognitive problems. [7][8][9][10] Thus, a novel treatment, effective enough to eliminate cancer cells with minimal influence on normal bodily functions, is needed, especially for pediatric AML patients. Large-scale sequencing and transcriptomics studies of AML patients have identified several novel targets for drug development.…”

Natural Products and Acute Myeloid Leukemia: A Review Highlighting Mechanisms of Action

“…Recent studies highlighted that midostaurin accompanied with standard chemotherapy significantly prolonged overall event-free survival for AML patients with a FMS-like tyrosine kinase 3 (FLT3) mutation [4]. While daunorubicin, idarubicin, cytarabine and doxorubicin remain the standard therapy for AML, the drug has been reported with a few cardiotoxic effects, a well-known risk factor for congestive heart failure [5]. AML is an incurable disease with relapse possibilities and conventional therapies have shown side-effects such as hepatotoxicity, myelosuppression, and tumor lysis syndrome [6].…”

Epigenetic Changes Associated With Anthracycline‐Induced Cardiotoxicity

“…Doxorubicin is used to treat numerous cancers for both adult and pediatric populations, such as breast cancer, Hodgkin's lymphoma in adults, and acute lymphoblastic leukemia, and acute myeloid leukemia in pediatrics. 6,7 Daunorubicin is usually utilized in the treatment of acute leukemias in both adults and pediatrics, whereas epirubicin is mostly used for breast cancer in adults and relapsed sarcoma in children. 8 Idarubicin use in adult and pediatric cancers is still minimal compared with the other anthracyclines.…”

“…There are currently four anthracyclines that are commonly used in clinical practice: doxorubicin, daunorubicin, epirubicin, and idarubicin, with doxorubicin being the most common. Doxorubicin is used to treat numerous cancers for both adult and pediatric populations, such as breast cancer, Hodgkin’s lymphoma in adults, and acute lymphoblastic leukemia, and acute myeloid leukemia in pediatrics 6,7 . Daunorubicin is usually utilized in the treatment of acute leukemias in both adults and pediatrics, whereas epirubicin is mostly used for breast cancer in adults and relapsed sarcoma in children 8 .…”