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Erschienen in: Current Treatment Options in Cardiovascular Medicine 7/2016

01.07.2016 | Cardio-oncology (M Fradley, Section Editor)

Late Cardiotoxicity: Issues for Childhood Cancer Survivors

verfasst von: Jyothsna Akam-Venkata, MBBS, Vivian I. Franco, MPH, Steven E. Lipshultz, MD

Erschienen in: Current Treatment Options in Cardiovascular Medicine | Ausgabe 7/2016

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Opinion statement

Cardiovascular-related morbidity is a substantial health burden in survivors of childhood cancers. This burden is gaining importance as this population increases through advancements in therapy. Anthracyclines are commonly used agents that are known to cause late cardiotoxicity. Cardiotoxicity is also increased by other risk factors, such as concurrent radio- or chemotherapy, younger age at diagnosis, female sex, comorbidities, lifestyle factors, and genetic factors, such as hemochromatosis gene mutations. Treatment of late cardiotoxicity depends on the type of cardiac abnormalities and consists of pharmacotherapy, mechanical support, or heart transplantation. Because cardiotoxicity is progressive and often irreversible, prevention, risk reduction, and early detection are of utmost importance. The cardioprotectant dexrazoxane decreases anthracycline cardiotoxicity. Screening for other risk factors at the time of diagnosis may identify risk that when present, if used to tailor therapy, may reduce the severity of cardiac damage. The effects of exercise and other lifestyle changes in reducing the cardiovascular diseases in cancer survivors are unclear. However, it may be beneficial to encourage survivors to engage in physical activity tailored to survivor medical status, but with close monitoring.
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62.••
Zurück zum Zitat Lipshultz SE, Lipsitz SR, Kutok JL, Miller TL, Colan SD, Neuberg DS, et al. Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer. 2013;119(19):3555–62. This study identified the correlation between the carriers of HFE gene mutations and the incidence of cardiotoxicity.PubMedPubMedCentralCrossRef Lipshultz SE, Lipsitz SR, Kutok JL, Miller TL, Colan SD, Neuberg DS, et al. Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer. 2013;119(19):3555–62. This study identified the correlation between the carriers of HFE gene mutations and the incidence of cardiotoxicity.PubMedPubMedCentralCrossRef
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Zurück zum Zitat Krajinovic M, Elbared J, Drouin S, Bertout L, Rezgui A, Ansari M et al. Polymorphisms of ABCC5 and NOS3 genes influence doxorubicin cardiotoxicity in survivors of childhood acute lymphoblastic leukemia. Pharmacogenomics J. 2015;1–6. This study identified two new polymorphisms in genes ABCC5 and NOS3 which may contribute to anthracycline-related cardiotoxicity. Krajinovic M, Elbared J, Drouin S, Bertout L, Rezgui A, Ansari M et al. Polymorphisms of ABCC5 and NOS3 genes influence doxorubicin cardiotoxicity in survivors of childhood acute lymphoblastic leukemia. Pharmacogenomics J. 2015;1–6. This study identified two new polymorphisms in genes ABCC5 and NOS3 which may contribute to anthracycline-related cardiotoxicity.
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Zurück zum Zitat Lipshultz SE, Adams MJ, Colan SD, Constine LS, Herman EH, Hsu DT, et al. Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association. Circulation. 2013;128(17):1927–95. Reviewed nearly 650 scientific works, the endorsed American Heart Association and American Academy of Pediatrics Scientific Statement.PubMedCrossRef Lipshultz SE, Adams MJ, Colan SD, Constine LS, Herman EH, Hsu DT, et al. Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association. Circulation. 2013;128(17):1927–95. Reviewed nearly 650 scientific works, the endorsed American Heart Association and American Academy of Pediatrics Scientific Statement.PubMedCrossRef
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84.••
Zurück zum Zitat Lipshultz SE, Miller TL, Scully RE, Lipsitz SR, Rifai N, et al. Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia: associations with long-term echocardiographic outcomes. J Clin Oncol. 2012;30:1042–9. A randomized clinical trial, which validated cTnT and NT-proBNP as surrogate endpoints of late abnormalities of left ventricular structure and function in long-term survivors and are useful early indicators of cardiotoxicity.PubMedPubMedCentralCrossRef Lipshultz SE, Miller TL, Scully RE, Lipsitz SR, Rifai N, et al. Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia: associations with long-term echocardiographic outcomes. J Clin Oncol. 2012;30:1042–9. A randomized clinical trial, which validated cTnT and NT-proBNP as surrogate endpoints of late abnormalities of left ventricular structure and function in long-term survivors and are useful early indicators of cardiotoxicity.PubMedPubMedCentralCrossRef
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Zurück zum Zitat Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civelli M, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation. 2006;114(23):2474–81.PubMedCrossRef Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civelli M, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation. 2006;114(23):2474–81.PubMedCrossRef
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Zurück zum Zitat Asselin BL, Devidas M, Chen L, Franco VI, Pullen J, Borowitz MJ, et al. Cardioprotection and safety of dexrazoxane in patients treated for newly diagnosed T-cell acute lymphoblastic leukemia or advanced-stage lymphoblastic non-Hodgkin lymphoma: a report of the Children’s Oncology Group randomized trial 9404. J Clin Oncol. 2015. (In press). Randomized controlled trial that demonstrated (i) the efficacy of dexrazoxane in cardioprotection and (ii) that dexrazoxane does not impair the antitumor activity of doxorubicin. Asselin BL, Devidas M, Chen L, Franco VI, Pullen J, Borowitz MJ, et al. Cardioprotection and safety of dexrazoxane in patients treated for newly diagnosed T-cell acute lymphoblastic leukemia or advanced-stage lymphoblastic non-Hodgkin lymphoma: a report of the Children’s Oncology Group randomized trial 9404. J Clin Oncol. 2015. (In press). Randomized controlled trial that demonstrated (i) the efficacy of dexrazoxane in cardioprotection and (ii) that dexrazoxane does not impair the antitumor activity of doxorubicin.
96.••
Zurück zum Zitat Chow EJ, Asselin BL, Schwartz CL, Doody DR, Leisenring WM, Aggarwal S, et al. Late mortality after dexrazoxane treatment: a report from the Children’s Oncology Group. J Clin Oncol. 2015;33(44):2639–45. Longitudinal study involving follow-up of patients with ALL that showed that dexrazoxane use was not associated with deaths from acute myeloid leukemia/myelodysplasia or cardiovascular events.PubMedPubMedCentralCrossRef Chow EJ, Asselin BL, Schwartz CL, Doody DR, Leisenring WM, Aggarwal S, et al. Late mortality after dexrazoxane treatment: a report from the Children’s Oncology Group. J Clin Oncol. 2015;33(44):2639–45. Longitudinal study involving follow-up of patients with ALL that showed that dexrazoxane use was not associated with deaths from acute myeloid leukemia/myelodysplasia or cardiovascular events.PubMedPubMedCentralCrossRef
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103.••
Zurück zum Zitat Lipshultz SE, Miller TL, Gerschenson M, Neuberg DS, Stevenson KE, Franco VI, et al. Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors. Cancer. 2016. doi: 10.1002/cncr.29872. Epub ahead of print. Doxorubicin-treated childhood cancer survivors had increased peripheral blood mononuclear cell mitochondrial DNA copies/cell, and concomitant use of dexrazoxane was associated with lower mitochondrial DNA copies/cell. With no difference in oxidative phosphorylation activity between the groups, this study suggests a possible compensatory increase in mitochondrial DNA copies/cell to maintain mitochondrial function in the setting of mitochondrial dysfunction. Lipshultz SE, Miller TL, Gerschenson M, Neuberg DS, Stevenson KE, Franco VI, et al. Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors. Cancer. 2016. doi: 10.​1002/​cncr.​29872. Epub ahead of print. Doxorubicin-treated childhood cancer survivors had increased peripheral blood mononuclear cell mitochondrial DNA copies/cell, and concomitant use of dexrazoxane was associated with lower mitochondrial DNA copies/cell. With no difference in oxidative phosphorylation activity between the groups, this study suggests a possible compensatory increase in mitochondrial DNA copies/cell to maintain mitochondrial function in the setting of mitochondrial dysfunction.
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Metadaten
Titel
Late Cardiotoxicity: Issues for Childhood Cancer Survivors
verfasst von
Jyothsna Akam-Venkata, MBBS
Vivian I. Franco, MPH
Steven E. Lipshultz, MD
Publikationsdatum
01.07.2016
Verlag
Springer US
Erschienen in
Current Treatment Options in Cardiovascular Medicine / Ausgabe 7/2016
Print ISSN: 1092-8464
Elektronische ISSN: 1534-3189
DOI
https://doi.org/10.1007/s11936-016-0466-6

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