Anthracycline-Related Cardiotoxicity in Patients with Acute Myeloid Leukemia and Down Syndrome: A Literature Review

Hefti, Erik; Blanco, Javier G.

doi:10.1007/s12012-015-9307-1

Cited by 26 publications

(34 citation statements)

References 35 publications

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“…By contrast, deletion of type 1 carbonyl reductase (CBR1) reduces alcohol metabolite production and susceptibility to cardiotoxicity 20. Elevated expression of CBR1 may be responsible for the higher rates of heart failure in anthracycline-treated patients with Down’s syndrome 21. Childhood cancer survivors who were homozygous for a gain-of-function CBR3 allele were more likely to have developed anthracycline cardiotoxicity in one retrospective study 22…”

Section: Anthracycline-induced Cardiotoxicitymentioning

confidence: 99%

Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention

Henriksen

2017

Heart

403

260

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Anthracycline chemotherapy causes dose-related cardiomyocyte injury and death leading to left ventricular dysfunction. Clinical heart failure may ensue in up to 5% of high-risk patients. Improved cancer survival together with better awareness of the late effects of cardiotoxicity has led to growing recognition of the need for surveillance of anthracycline-treated cancer survivors with early intervention to treat or prevent heart failure. The main mechanism of anthracycline cardiotoxicity is now thought to be through inhibition of topoisomerase 2β resulting in activation of cell death pathways and inhibition of mitochondrial biogenesis. In addition to cumulative anthracycline dose, age and pre-existing cardiac disease are risk markers for cardiotoxicity. Genetic susceptibility factors will help identify susceptible patients in the future. Cardiac imaging with echocardiographic measurement of global longitudinal strain and cardiac troponin detect early myocardial injury prior to the development of left ventricular dysfunction. There is no consensus on how best to monitor anthracycline cardiotoxicity although guidelines advocate quantification of left ventricular ejection fraction before and after chemotherapy with additional scanning being justified in high-risk patients. Patients developing significant left ventricular dysfunction with or without clinical heart failure should be treated according to established guidelines. Liposomal encapsulation reduces anthracycline cardiotoxicity. Dexrazoxane administration with anthracycline interferes with binding to topoisomerase 2β and reduces both cardiotoxicity and subsequent heart failure in high-risk patients. Angiotensin inhibition and β-blockade are also protective and appear to prevent the development of left ventricular dysfunction when given prior or during chemotherapy in patients exhibiting early signs of cardiotoxicity.

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Section: Anthracycline-induced Cardiotoxicitymentioning

confidence: 99%

Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention

Henriksen

2017

Heart

403

260

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“…For example, anthracyclines used in AML therapy may lead to cardiac toxicity, with implications for physical functioning after treatment. 45 Infectious complications may impact functional outcomes. 6 Neurocognitive functioning, including neurocognitive late effects after cancer treatment, also have implications for QOL.…”

Section: Introductionmentioning

confidence: 99%

Health-related Quality of Life (HR-QOL) and Chronic Health Conditions in Survivors of Childhood Acute Myeloid Leukemia (AML) with Down Syndrome (DS): A Report From the Children’s Oncology Group

Schultz

Chen

Kunin‐Batson

et al. 2017

Journal of Pediatric Hematology/Oncology

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Survival rates for children with Down syndrome (DS) and acute myeloid leukemia (AML) are high; however, little is known regarding the health-related quality of life (HR-QOL) of these survivors. Individuals who survived ≥5 years following diagnosis of childhood AML were invited to complete parent or patient-report surveys measuring HR-QOL and chronic health conditions. Twenty-six individuals with DS had a median age at diagnosis of 1.8 years (range, 0.77-10.9) and median age at interview of 15 years (range 8.3-27.6). Participants with DS and AML were compared to AML survivors without DS whose caregiver completed a HR-QOL survey (CHQ-PF50). Seventy-seven percent of survivors with DS reported ≥1 chronic health condition compared to 50% of AML survivors without DS (p=0.07). Mean physical and psychosocial QOL scores for children with DS and AML were statistically lower than the population mean, though not discrepant from AML survivors without DS. Although the overall prevalence of chronic health conditions in survivors with DS is higher than in survivors without DS, prior studies of children with DS have reported similarly high rates of chronic health conditions, suggesting that AML therapy may not substantially increase this risk.

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“…For example, the pharmacokinetics of doxorubicin was not shown to be significantly altered in patients with DS; however, there are still doxorubicin-specific toxicities that have been reported to occur more often in these patients 7 . Specifically, patients with DS and leukemia may be at a higher risk for anthracycline-related cardiotoxicity 8 . The intra-cardiac synthesis of anthracycline alcohol metabolites (e.g., daunorubicinol) by carbonyl reductases (CBRs) and aldo-keto reductases (AKRs) contributes to the pathogenesis of cardiotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…It has multiple mechanisms of action including DNA intercalation, topoisomerase II inhibition, and generation of damaging oxidative radicals 28 . Anthracycline-related cardiotoxicity has been studied in patients with DS in the past; however, the pharmacokinetics of anthracyclines (including doxorubicin) in DS is seldom considered 8 . In the previously discussed study by Eksborg et al, the authors mentioned a single patient with DS treated with doxorubicin that displayed decreased clearance, but data were not shown 26 .…”

Section: Antileukemic Agents That Have Not Shown Altered Pharmacokinementioning

confidence: 99%

Pharmacokinetics of Chemotherapeutic Drugs in Pediatric Patients With Down Syndrome and Leukemia

Hefti

Blanco²

2016

Journal of Pediatric Hematology/Oncology

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Children with Down syndrome (DS) have a 10 – 30 fold increased risk of developing acute myeloid leukemia or acute lymphoblastic leukemia. Patients with DS and leukemia are treated with the same chemotherapeutic agents as patients without DS. Treatment regimens for pediatric leukemia comprise multiple cytotoxic drugs including methotrexate, doxorubicin, vincristine, cytarabine, and etoposide. There have been reports of increased toxicity, as well as altered therapeutic outcomes in pediatric patients with DS and leukemia. This review is focused on the pharmacokinetics of cytotoxic drugs in pediatric patients with leukemia and DS. The available literature suggests that methotrexate and thioguanine display altered pharmacokinetic parameters in pediatric patients with DS. It has been hypothesized that the variable pharmacokinetics of these drugs may contribute to the increased incidence of treatment-related toxicities seen in DS. Data from a small number of studies suggest that the pharmacokinetics of vincristine, etoposide, doxorubicin, and busulfan are similar between patients with and without DS. Definitive conclusions regarding the pharmacokinetics of cytotoxic drugs in pediatric patients with leukemia and DS are difficult to reach due to limitations in the available studies.

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Anthracycline-Related Cardiotoxicity in Patients with Acute Myeloid Leukemia and Down Syndrome: A Literature Review

Cited by 26 publications

References 35 publications

Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention

Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention

Health-related Quality of Life (HR-QOL) and Chronic Health Conditions in Survivors of Childhood Acute Myeloid Leukemia (AML) with Down Syndrome (DS): A Report From the Children’s Oncology Group

Pharmacokinetics of Chemotherapeutic Drugs in Pediatric Patients With Down Syndrome and Leukemia

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