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

Abstract

Summary: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. Bone Marrow Transplantation (2000) 25, 885-894.

Cardiac toxicity of high-dose chemotherapy

“…In at least seven studies, LVEF measured at rest was unable to predict future cardiac toxicity. 17,28,79,80,100,104,105 One of these studies also showed that measurement of cardiac reserve during exercise could not predict cardiac morbidity or mortality. 104 On the other hand, three studies reported a significant association between pre-transplant LVEF and cardiotoxicity 18,54,77 and two more described a trend in the same direction.…”

“…Other authors found a trend towards significance also. 78,80 Besides the inconsistent data in the literature, the potential contribution of previous anthracycline exposure to HD chemotherapy-associated cardiac toxicity should be reconsidered based upon recent insights about the progressive establishment of cardiac damage by anthracyclines. The long known assumption that the incidence of chronic cardiomyopathy is minimized by restricting the cumulative doxorubicin dose less than 400 mg/m 281 has been recently challenged.…”

“…Thorough pre-HD chemotherapy cardiologic evaluation including 2D echo 28,88 History of anthracycline exposure Thorough pre-HD chemotherapy cardiologic evaluation including 2D echo restriction of total anthracycline exposure to o400 mg/m 2 use of cardioprotectors (ie dexrazoxane) use of liposomal formulations of anthracyclines 22,78,80,[84][85][86][87] Older High-dose therapy cardiac toxicity P Morandi et al months. 103 Finally, in 11 patients whose pre-transplant LVEF was o50%, no signs of heart failure were recorded at prolonged follow-up after HSC transplantation.…”

Acute left ventricular failure following melphalan and fludarabine conditioning

“…Twenty-one patients have undergone NMSCT following conditioning with melphalan and fludarabine at our institution for multiple myeloma (11), chronic lymphocytic leukaemia (3), chronic myeloid leukaemia (2), acute lymphoblastic leukaemia (2), non-Hodgkin lymphoma (1), acute myeloblastic leukaemia (1), and paroxysmal nocturnal haemoglobinaemia (1). All received a total fludarabine dose of 150 mg/m 2 over 5 days (day −6 to day −2 inclusive) in addition to melphalan 120 mg/m 2 (four cases) or 140 mg/m 2 (17 cases) on day −1.…”

Clinical Significance of Cyclophosphamide-induced Cardiotoxicity

“…Radiation therapy to the chest wall may cause direct cardiac toxicity or augment the effects of chemotherapy. Some reports indicated that prior radiation therapy to the mediastinum or chest wall is an independent predictor of cardiotoxicity in patients with lymphoma and breast cancer undergoing high-dose chemotherapy (6,7).…”