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Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood

Els Vandecruys (UGent) , Veerle Mondelaers (UGent) , Daniël De Wolf (UGent) , Yves Benoit (UGent) and Bert Suys
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Abstract
Introduction Late cardiotoxicity is a known complication of anthracycline therapy but the long-term effects of low cumulative doses are not well documented. We studied late cardiotoxicity in survivors of childhood acute lymphoblastic leukemia (ALL) treated with low anthracycline doses 10 to 20 years earlier. Methods Seventy-seven ALL survivors who received a cumulative anthracycline dose <250 mg/m(2) and were at least 10 years after treatment were evaluated for signs of clinical heart failure. Cardiac function was assessed by echocardiography including tissue Doppler measurements of the septal mitral annulus in 37 ALL survivors 10.6-18.3 years (median 13.3 years) after anthracycline treatment with cumulative doses of 180 (n=19) or 240 mg/m(2) (n=18). The control group consisted of 30 healthy volunteers matched for age, sex, BSA, and BMI. Results No clinical relevant cardiotoxicity was found. Left ventricular shortening fraction (SF) was significantly reduced in male ALL survivors. Three of the 19 male ALL survivors had an SF below 30%. Male ALL survivors showed a significantly lower early filling velocity to atrial contraction velocity ratio but myocardial velocity during early filling was comparable between patients and controls. ALL survivors had a significantly longer isovolumetric relaxation time (IVRT). Thirty percent of the ALL survivors have an abnormal IVRT compared to the normal range of the controls. Conclusion and implications for cancer survivors At a median of 13.3 years after exposure to cumulative doses of anthracyclines of 180 or 240 mg/m(2), no clinical relevant cardiotoxicity was found but subclinical cardiac abnormalities were present in 30% of the patients.
Keywords
HEART-FAILURE, SURVIVORS, CANCER, CHILDREN, Anthracycline-related cardiotoxicity, Late effects, ALL, Cardiotoxicity after cancer therapy, ECHOCARDIOGRAPHY, STRESS

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Chicago
Vandecruys, Els, Veerle Mondelaers, Daniël De Wolf, Yves Benoit, and Bert Suys. 2012. “Late Cardiotoxicity After Low Dose of Anthracycline Therapy for Acute Lymphoblastic Leukemia in Childhood.” Journal of Cancer Survivorship-research and Practice 6 (1): 95–101.
APA
Vandecruys, E., Mondelaers, V., De Wolf, D., Benoit, Y., & Suys, B. (2012). Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood. JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE, 6(1), 95–101.
Vancouver
1.
Vandecruys E, Mondelaers V, De Wolf D, Benoit Y, Suys B. Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood. JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE. 2012;6(1):95–101.
MLA
Vandecruys, Els, Veerle Mondelaers, Daniël De Wolf, et al. “Late Cardiotoxicity After Low Dose of Anthracycline Therapy for Acute Lymphoblastic Leukemia in Childhood.” JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE 6.1 (2012): 95–101. Print.
@article{2138964,
  abstract     = {Introduction Late cardiotoxicity is a known complication of anthracycline therapy but the long-term effects of low cumulative doses are not well documented. We studied late cardiotoxicity in survivors of childhood acute lymphoblastic leukemia (ALL) treated with low anthracycline doses 10 to 20 years earlier. 
Methods Seventy-seven ALL survivors who received a cumulative anthracycline dose {\textlangle}250 mg/m(2) and were at least 10 years after treatment were evaluated for signs of clinical heart failure. Cardiac function was assessed by echocardiography including tissue Doppler measurements of the septal mitral annulus in 37 ALL survivors 10.6-18.3 years (median 13.3 years) after anthracycline treatment with cumulative doses of 180 (n=19) or 240 mg/m(2) (n=18). The control group consisted of 30 healthy volunteers matched for age, sex, BSA, and BMI. 
Results No clinical relevant cardiotoxicity was found. Left ventricular shortening fraction (SF) was significantly reduced in male ALL survivors. Three of the 19 male ALL survivors had an SF below 30\%. Male ALL survivors showed a significantly lower early filling velocity to atrial contraction velocity ratio but myocardial velocity during early filling was comparable between patients and controls. ALL survivors had a significantly longer isovolumetric relaxation time (IVRT). Thirty percent of the ALL survivors have an abnormal IVRT compared to the normal range of the controls. 
Conclusion and implications for cancer survivors At a median of 13.3 years after exposure to cumulative doses of anthracyclines of 180 or 240 mg/m(2), no clinical relevant cardiotoxicity was found but subclinical cardiac abnormalities were present in 30\% of the patients.},
  author       = {Vandecruys, Els and Mondelaers, Veerle and De Wolf, Dani{\"e}l and Benoit, Yves and Suys, Bert},
  issn         = {1932-2259},
  journal      = {JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE},
  language     = {eng},
  number       = {1},
  pages        = {95--101},
  title        = {Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood},
  url          = {http://dx.doi.org/10.1007/s11764-011-0186-6},
  volume       = {6},
  year         = {2012},
}

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