Myocardial Infarction Mortality Risk After Treatment for Hodgkin Disease: A Collaborative British Cohort Study

Section of Epidemiology, Sir Richard Doll Building, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Journal of the National Cancer Institute (Impact Factor: 12.58). 03/2007; 99(3):206-14. DOI: 10.1093/jnci/djk029
Source: PubMed


Myocardial infarction is a major cause of excess long-term mortality in survivors of Hodgkin disease, but limited information exists on the effects of specific chemotherapy regimens used to treat these patients on their risk of death from myocardial infarction.
We followed a cohort of 7033 Hodgkin disease patients who were treated in Britain from November 1, 1967, through September 30, 2000, and compared their risk of myocardial infarction mortality with that in the general population of England and Wales. All statistical tests were two-sided.
A total of 166 deaths from myocardial infarction occurred in the cohort, statistically significantly more than expected (standardized mortality ratio [SMR] = 2.5, 95% confidence interval [CI] = 2.1 to 2.9), with an absolute excess risk of 125.8 per 100,000 person-years. Standardized mortality ratios decreased sharply with older age at first treatment, but absolute excess risks of death from myocardial infarction increased with older age up to age 65 years at first treatment. The statistically significantly increased risk of myocardial infarction mortality persisted through to 25 years after first treatment. Risks were increased statistically significantly and independently for patients who had been treated with supradiaphragmatic radiotherapy, anthracyclines, or vincristine. Risk was particularly high for patients treated with the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (SMR = 9.5, 95% CI = 3.5 to 20.6). Risk at 20 or more years after first treatment was particularly great for patients who had received supradiaphragmatic radiotherapy and vincristine without anthracyclines (SMR = 14.8, 95% CI = 4.8 to 34.5).
The risk of death from myocardial infarction after treatment for Hodgkin disease remains high for at least 25 years. The increased risks are related to supradiaphragmatic radiotherapy but may also be related to anthracycline and vincristine treatment.

Download full-text


Available from: Craig D Higgins,
39 Reads
  • Source
    • "Notch-1 regulates the fate of cardiac progenitor cells (CPCs) and stimulates proliferation of cardiac myocytes [29], [30]. Previous studies have shown that after treatment with DOX, Notch-1 receptor expression levels in CPCs are low compared with its ligands, delta-like 3 and jagged [5]. Thus, we wanted to study the expression of Notch-1 in DIC-post MI hearts. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Unlabelled: Doxorubicin (DOX), an effective chemotherapeutic drug used in the treatment of various cancers, is limited in its clinical applications due to cardiotoxicity. Recent studies suggest that transplanted adult stem cells inhibit DOX-induced cardiotoxicity. However, the effects of transplanted embryonic stem (ES) and induced pluripotent stem (iPS) cells are completely unknown in DOX-induced left ventricular dysfunction following myocardial infarction (MI). In brief, C57BL/6 mice were divided into five groups: Sham, DOX-MI, DOX-MI+cell culture (CC) media, DOX-MI+ES cells, and DOX-MI+iPS cells. Mice were injected with cumulative dose of 12 mg/kg of DOX and 2 weeks later, MI was induced by coronary artery ligation. Following ligation, 5×10(4) ES or iPS cells were delivered into the peri-infarct region. At day 14 post-MI, echocardiography was performed, mice were sacrificed, and hearts were harvested for further analyses. Our data reveal apoptosis was significantly inhibited in ES and iPS cell transplanted hearts compared with respective controls (DOX-MI+ES: 0.48±0.06% and DOX-MI+iPS: 0.33±0.05% vs. Dox-mi: 1.04±0.07% and DOX-MI+CC: 0.96±0.21%; p<0.05). Furthermore, a significant increase in levels of Notch-1 (p<0.05), Hes1 (p<0.05), and pAkt (p<0.05) were observed whereas a decrease in the levels of PTEN (p<0.05), a negative regulator of Akt, was evident following stem cell transplantation. Moreover, hearts transplanted with stem cells demonstrated decreased vascular and interstitial fibrosis (p<0.05) as well as MMP-9 expression (p<0.01) compared with controls. Additionally, heart function was significantly improved (p<0.05) in both cell-transplanted groups. In conclusion, our data show that transplantation of ES and iPS cells blunt DOX-induced adverse cardiac remodeling, which is associated with improved cardiac function, and these effects are mediated by the Notch pathway.
    PLoS ONE 07/2014; 9(7):e101024. DOI:10.1371/journal.pone.0101024 · 3.23 Impact Factor
    • "The presence of significant lesions and silent ischemia may lead to myocardial infarction and is associated with increased cardiac related mortality. In a report of 7033 patients successfully treated for Hodgkin disease and a mean follow-up of 11.2 years, the standardized mortality ratio secondary to myocardial infarction was 3.2 for those who were treated with mediastinal irradiation.[46] We may conclude that the adjunction of mediastinal irradiation in the treatment protocols of these patients may accelerate the development of CAD. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ligation and dissection of internal mammary vessels is the most under-estimated complication of anterior mediastinotomy. However, patients requiring anterior mediastinotomy may experience long survival that makes the development of ischemic heart disease throughout their life possible. Therefore, the un-judicial sacrifice of the internal mammary pedicle may deprive them from the benefit to have their internal mammary artery used as a graft in order to successfully bypass severe left anterior descending artery stenoses. We recommend the preservation of the internal mammary pedicle during anterior mediastinotomy, which should be a common message among our colleagues from the beginning of their training.
    Annals of Thoracic Medicine 07/2014; 9(3):138-43. DOI:10.4103/1817-1737.134067 · 1.80 Impact Factor
  • Source
    • "Appropriately, an “as treated” analysis was performed (but not reported in the meeting abstract). With this more realistic analysis, the 3-year PFS was 97 % for the combined modality arm compared to only 90.7 % with chemotherapy alone (HR = 2.39, [13], p = 0.03). Thus, in this study, like H10F and H10U, omitting RT even for negative PET led to an inferior disease control. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The standard treatment of early-stage Hodgkin lymphoma (ESHL) as recommended by most national guidelines is combined modality treatment (CMT) that includes a short course ABVD followed by a small field of low dose radiotherapy (RT). Recently a trend to treat patients with more chemotherapy alone has been promoted by some claiming that chemotherapy alone is good enough, and the overall survival is similar. These arguments need to be carefully examined, and the risk of more chemotherapy upfront and salvage considered. The suggestion that interim PET will identify patients that can have similar results with chemotherapy alone has recently been questioned by the results of both European and UK studies. It is the subject of this critical review.
    Current Hematologic Malignancy Reports 06/2014; 9(3). DOI:10.1007/s11899-014-0222-5 · 2.20 Impact Factor
Show more