Cardiac and pulmonary toxicity in patients undergoing high-dose chemotherapy for lymphoma and breast cancer: prognostic factors

Bone Marrow Transplant. 2000 Apr;25(8):885-94. doi: 10.1038/sj.bmt.1702234.


We sought to define risk factors predisposing breast cancer and lymphoma patients to cardiac and pulmonary toxicity when undergoing high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR). Additionally, we evaluated in depth the predictive value of the ejection fraction measured prior to HDC in determining cardiac toxicity. In this retrospective analysis, 24 variables were examined in 138 patients undergoing HDC and ASCR from 1990 until 1995. Logistic regression models were used to model the probability of experiencing cardiac and pulmonary toxicity as a function of the 24 prognostic covariates. Cardiac toxicity occurred in 12% of patients and pulmonary toxicity in 24% of patients. Bivariate analyses showed that patients with lymphoma (as opposed to breast cancer) and those with a higher cardiac risk factor score were more likely to experience cardiac toxicity. Multivariate logistic regression models predicted lymphoma and older age to be risk factors for cardiac toxicity. History of an abnormal ejection fraction and higher doses of anthracyclines prior to HDC may also contribute to cardiac toxicity. Pulmonary toxicity occurred more commonly in lymphoma than breast cancer patients, likely due to the busulfan used in the HDC regimen. No other risk factors for pulmonary toxicity were identified. We conclude that older patients with lymphoma should be carefully evaluated prior to being accepted for HDC programs. Older patients with breast cancer may tolerate this procedure well. There is a trend towards cardiac toxicity in patients with a past history of low ejection fraction, although seemingly poor cardiac risk patients may fare well with HDC if carefully selected with the aid of a thorough cardiac evaluation.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / toxicity*
  • Bone Marrow Transplantation / adverse effects
  • Breast Neoplasms / complications*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / epidemiology
  • Cyclophosphamide / therapeutic use
  • Cyclophosphamide / toxicity
  • Doxorubicin / therapeutic use
  • Doxorubicin / toxicity
  • Female
  • Heart Diseases / chemically induced*
  • Heart Diseases / epidemiology
  • Hematopoietic Stem Cell Mobilization
  • Humans
  • Incidence
  • Logistic Models
  • Lung Diseases / chemically induced*
  • Lung Diseases / epidemiology
  • Lung Diseases / etiology
  • Lymphoma / complications*
  • Lymphoma / drug therapy*
  • Lymphoma / epidemiology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Smoking / adverse effects
  • Stroke Volume
  • Transplantation Conditioning / adverse effects
  • Transplantation, Autologous / adverse effects


  • Doxorubicin
  • Cyclophosphamide