Cardiorespiratory status after treatment for acute lymphoblastic leukemia

The use of certain chemotherapeutic agents is associated with dose-related cardiotoxicity and, potentially, with restrictive lung disease. Therefore, we assessed the cardiopulmonary status and exercise capacity of 19 patients (pts; 9M:10F) 1.1 to 7.1 years (mean 4.6 +/- 1.5 years) after successful treatment of acute lymphoblastic leukemia (ALL) with Dana Farber Cancer Institute protocols. As body mass and nutritional status may influence exercise capacity, we also evaluated their anthropometric status and the plasma levels of rapid turnover proteins. Seven pts designated as "standard risk for relapse" (SR) had received low cumulative doses of doxorubicin (50 +/- 21 mg/m2), while twelve pts at "high or very high risk for relapse" (HR/VHR) had received higher doses (349 +/- 16 mg/m2). The evaluations included a questionnaire, anthropometric assessments, echocardiography, pulmonary function studies, exercise testing, and nutritional assays. Patients' data were compared with published normative data or with control values from our laboratories. In addition, we compared SR pt data with HR/VHR pt data. No pt had overt symptoms or signs of cardiorespiratory compromise. The pts had a higher percent of body fat than age-matched healthy controls (29.7 +/- 7.9% vs. 20 +/- 6%; P < 0.001). On echocardiography, cardiac systolic function was within normal limits in all. However, HR/VHR pts had lower left ventricular (LV) shortening fractions than SR pts (P < 0.05). LV filling velocity, indicative of diastolic function (the E/A ratio), was normal in most pts. Pulmonary function studies were normal. Exercise capacity was below predicted in most cases but heart rates at peak exercise and leg muscle function were within normal limits, suggesting a deconditioned state. Plasma levels of rapid turnover proteins were also normal. Despite lack of overt morbidity in our pt population, subtle abnormalities persist in cardiac function while pulmonary function is normal. Longitudinal studies will identify if further abnormalities or overt morbidity develop. In later years, continuing obesity and a sedentary state may contribute to clinically relevant heart disease.