Childhood Malignancy and Cardiotoxicity of Anthracyclines (original) (raw)
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Anthracycline-related cardiotoxicity: risk factors and therapeutic options in childhood cancers
Signa Vitae - A Journal In Intensive Care And Emergency Medicine, 2008
Anthracyclines play an important role in chemotherapeutic regimens for a wide spectrum of childhood tumors, but they can cause cytotoxic damage to cardiac cells, especially in combination with radiotherapy. Furthermore, cardiotoxicity increases with the cumulative dose and may lead to congestive heart failure and cardiomyopathy. Other factors, including age, pre-existing cardiac disease, length of follow-up, gender, route of administration, concomitant exposure to some chemotherapeutic drugs, trisomy 21 and black race, play a role in increasing the risk of cardiac dysfunction. The prevention of anthracycline-induced cardiotoxicity is mandatory as children are expected to survive for decades after being cured of their cancer. The purpose of this work is to point out the major risk factors of cardiotoxicity in children and to summarize some strategies to limit or prevent this complication and to treat the development of acute heart failure.
Background: Anthracycline induced cardiac complications are one of the most common causes of morbidity and mortality in childhood hemato-oncological malignancies despite recent advances in the diagnosis and treatment. Anthracycline causes cardio toxic effects during treatment when its level exceeds the cumulative dose. Aims and Objectives: This was aimed to evaluate cardiac complications with anthracycline and to determine associated electrocardiogram (ECG) and echocardiogram (ECHO) change with anthracycline in the hemato-oncological malignancies. Materials and Methods: The present study was conducted from January 2018 to December 2018 on sixty-nine diagnosed hemato-oncological malignancies between five to fifteen years irrespective of sex. A detailed history along with a complete blood count, biochemical investigations, chest x-ray, bone marrow aspiration, immunophenotype and other relevant investigations were performed. ECG, ECHO was done in all patients at initial presentation and during reassessment. The children were treated with the protocol UKALL-XII, Hyper-CVAD, R-CHOP, ATRA+doxorubicin, Doxorubicin+Cytarabine, ABVD. Blood level of anthracycline was done during reassessment. Results: Among the hematological malignancies, boys were 46 and girl 23. Acute lymphoblastic leukemia (ALL) was the most common 39.1% followed by acute myeloid leukemia (AML) 18.8% and Hodgkin's disease (HD) 17.3%. The mean cumulative dose of doxorubicin was 265.2±89.3 mg/m 2 and daunorubicin 270.6±59.6mg/m 2 among all malignancies. None of the patient found QRS duration more than 120 seconds. One child had QT interval more than 450 ms (p=0.001). The ECHO showed significant difference in ejection fraction (EF) during reassessment. Left ventricular dysfunction (less<50%) found in 17% children and significant reduction in EF (p=0.001) along with significant reduction in diastolic dysfunction (p=0.001).Ten (14%) children treated with R-CHOP, two (2.8%) Hyper-CVAD, twenty-five (36.2%) UKALL-XII, twelve (17.39%) ABVD, thirteen (18.8%) Doxorubicin+Cytarabine 3+7, and seven (10%) ATRA+ADM protocol. Most of the hematological malignancies treated with R-CHOP found left ventricular dysfunction. The left ventricular dysfunction in Hodgkin's disease was statistically significant (p=0.003).Four (66%) children had developed left ventricular dysfunction. Eight patients treated with doxorubicin developed left ventricular systolic dysfunction and only one with daunorubicin. Conclusions: The ECG, QRS voltage change, prolong QTc interval, and left ventricular systolic dysfunction are common in anthracycline treated hemato-oncological malignancies with cumulative dose ˃250 mg/m 2. Decrease QRS voltage more than 35% from base line was associated with left ventricular dysfunction in Hodgkin's disease.
Myocardial Changes in Childhood Cancer Patients Treated with Anthracyclines
2017
Background: Anthracycline-induced cardiotoxicity in survivors of childhood cancer initially presenting as sub-clinical cardiac abnormalities that, if left undetected or untreated, can lead to clinical cardiac dysfunction. The present study aimed to evaluate the early myocardial changes that develop with anthracycline therapy. Material and Methods: In this prospective study the preanthracycline and 6-months postanthracycline echocardiographic and electrocardiographic parameters were analyzed for cardiac dysfunction. The demographic information, including age, sex, type of anthracycline, and cumulative dose, were recorded, as well. Results: In this study, 115 patients with childhood cancer, including 81 males (70.4%) and 34 females (29.6%) with the mean age of 11.1±3.8 years were enrolled. Their normal baseline and 6-months postanthracycline echocardiographic and electrocardiographic parameters were compared for myocardial changes. Doxorubicin alone was used in 91 (79%) patients while daunorubicin alone in 24 (21%). Only 16 children (14%) received a high dose of anthracycline (cumulative dose > 300 mg/m 2). QTc interval significantly prolonged 6-months after chemotherapy than the baseline readings (P<0.001). There was a significant increase in the left ventricular dimensions, and all myocardial functional parameters were significantly deteriorated in children who received anthracycline (P<0.001). The incidence of cardiac dysfunction found more in female patients (20/28; 71.4%). Myocardial dysfunction was significantly higher among children who received a high cumulative dose of doxorubicin (P<0.001). Conclusion: The incidence of subclinical anthracycline-related cardiac dysfunction is high. Children treated with anthracycline require a long-term follow-up to identify and establish optimal prevention and management strategies that balance oncologic efficacy with long-term safety.
Cardio-Oncology, 2015
Background: Subacute cardiotoxicity, consisting of acute myocyte damage and associated left ventricular dysfunction, occurs early during anthracycline therapy. We investigated the impact of myocardial dysfunction, defined herein by a shortening fraction (SF) < 29 % at any time during or after anthracycline therapy, on late onset cardiomyopathy and all-cause mortality, among childhood cancer survivors exposed to anthracyclines. In addition, we sought to identify subpopulations of subjects at highest risk for cardiomyopathy and death from all causes. Methods: Five hundred thirty-one childhood cancer survivors exposed to anthracyclines were enrolled and studied on average 10 (1.4-27.3) years following their initial exposure. The medical records were reviewed to identify known risk factors associated with cardiotoxicity, including cumulative anthracycline dose, length of post-therapy interval, administration of other cardiotoxic medications (vinca alkaloids), previous heart disease, radiation dose to the heart, history of bone marrow transplantation, age at treatment, gender, systolic dysfunction, and history of congestive heart failure during anthracycline therapy. Results: Ninety subjects (16.9 %) developed SF < 29 % and 71 patients (13.4 %) died on average 10 years after initial exposure (range 1.4-27.3 years). Total cumulative dose (OR 3.27, 95 % CI 1.94, 5.49, p < 0.001) and bone marrow transplantation (OR 2.57, 95 % CI 1.24, 5.30, p = 0.01) were found to be statistically significant risk factors for development of myocardial dysfunction. There was a 3-fold increase in the odds of having a SF < 29 % at any point during or following cancer therapy if a subject underwent bone marrow transplantation or had a total cumulative dose anthracycline therapy ≥ 240 mg/m 2. The all-cause mortality ratio was almost seven-fold higher (95 % CI, 2.40-fold to 17.81-fold higher) if a subject developed systolic dysfunction, defined by a previous SF < 29 % anytime during or after anthracycline therapy. Nine deaths (12.7 %) were attributed to cardiovascular disease. The risk of dying as a result of cardiac disease also was significantly higher in individuals who had a SF < 29 % at any time during or after therapy. Conclusions: This study demonstrates an almost seven-fold increase in all cause mortality in pediatric cancer survivors with a history of anthracycline induced myocardial dysfunction defined as SF < 29 %.
Cardiovascular Effects in Childhood Cancer Survivors Treated with Anthracyclines
Cardiology Research and Practice, 2011
Anthracyclines are commonly used to treat childhood leukemias and lymphomas, as well as other malignancies, leading to a growing population of long-term childhood cancer survivors. However, their use is limited by cardiotoxicity, increasing survivors' vulnerability to treatment-related complications that can markedly affect their quality of life. Survivors are more likely to suffer from heart failure, coronary artery disease, and cerebrovascular accidents compared to the general population. The specific mechanisms of anthracycline cardiotoxicity are complex and remain unclear. Hence, determining the factors that may increase susceptibility to cardiotoxicity is of great importance, as is monitoring patients during and after treatment. Additionally, treatment and prevention options, such as limiting cumulative dosage, liposomal anthracyclines, and dexrazoxane, continue to be explored. Here, we review the cardiovascular complications associated with the use of anthracyclines in tre...