Isolated Left Ventricular Filling Abnormalities May Predict Interleukin-2-Induced Cardiovascular Toxicity

G. Citterio, G. Fragasso, E. Rossetti, G. Di Lucca, E. Bucci, M. Foppoli, R. Guerrieri, P. Matteucci, D. Polastri, U. Scaglietti, M. Tresoldi, S. L. Chierchia, C. Rugarli

Research output: Contribution to journalArticlepeer-review


Interleukin-2 (IL-2) is a cytokine with proven activity against metastatic renal cell carcinoma (RCC) and malignant melanoma (MM). The intravenous administration of high-dose IL-2 is limited by important cardiovascular side effects such as hypotension, fluid retention, arrhythmias, and myocardial chemia, which often cause dose reduction and/or treatment withdrawal. The occurrence of these toxic events is not predicted by routine pretreatment examinations. The aim of the present study was to test the reliability of serial echocardiography in predicting subsequent cardiac adverse effects in patients undergoing IL-2 administration. In 19 patients (15 men, 4 women; median age: 51 years, range 27-71 years; 10 affected by metastatic RCC and 9 affected by MM) we performed two-dimensional and Doppler echocardiography before and immediately after 28 continuous intravenous infusions (CIVI) of IL-2 at the dose of 18 MIU/m2/day for 4 days. Left ventricular systolic function and the diastolic transmitral flow pattern were assessed before and after IL-2 administration. Significant changes of two indexes of left ventricular filling were noted: a decrease of the ratio of maximal flow velocity in early diastole to that in late diastole (E/A) (basal: 1.12 ± 0.46, mean ± SD; posttreatment: 0.83 ± 0.27; p <0.01) and an increase of the percentage of the atrial contribution to left ventricular filling (basal: 37.75 ± 11.58%; posttreatment: 49.43 ± 16.48%; p <0.01).Eight major cardiovascular events causing IL-2 infusion withdrawal were observed (two ischemic electrocardiographic modifications, three grade III-IV hypotension, one atrial fibrillation, one pericardial effusion, one acute heart failure). These major cardiovascular events were observed more often when an abnormal basal E/A ratio <1.0 (p <0.05) was found. We conclude that Doppler transmitral flow pattern analysis before and subsequent to IL-2 infusion is a useful and easily available procedure for the monitoring of cardiac modifications during CIVI IL-2 administration. It might also predict a major cardiovascular event during IL-2 administration. Patients with basal E/A ratio

Original languageEnglish
Pages (from-to)134-141
Number of pages8
JournalJournal of Immunotherapy
Issue number2
Publication statusPublished - 1996


  • Cardiovascular toxicity
  • Diastolic function
  • Doppler echocardiography
  • Immunotherapy
  • Interleukin-2

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Pharmacology


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