Echocardiographic (Echo) monitoring of myocardial injury during doxorubicin (DOX) therapy for childhood acute lymphoblastic leukemia (ALL)

Abstract

8505 Background: Myocardial injury echo monitoring is recommended during DOX. We examined the relationship between echo-determined left ventricular (LV) function & structure & serum cardiac troponin T (cTnT), a sensitive & specific measure of myocardial injury during DOX and continuation therapy for ALL. Methods: 206 high-risk ALL pts were randomized on DFCI protocol 95–001 to receive DOX alone (30 mg/m2/dose, n=101 pts, 300 mg/m2 cumulative dose), or dexrazoxane (DEX) (300 mg/m2) followed by DOX (n=105 pts). cTnT was assayed before, during, & after DOX in 76 DOX-only pts & 82 DEX-DOX pts with 2377 samples (mean-15.1 samples/pt). Pts with cTnT had 462 echos (median-2.5 echos/pt) while receiving (n=162) or at 198 days (median) after DOX (n=164, during continuation). Echo z-scores (standard deviations ± the predicted value) of LV function (fractional shortening [FS] & contractility) & structure (end-diastolic diameter) were determined. In this substudy the echo & cTnT results were compared. Results: Elevations of cTnT (>0.01 ng/mL) occurred in 35% (55/158) of pts. Pts treated with DOX alone were significantly more likely to have elevated cTnT samples (50 vs 21%; P<0.001). Echos prior to DOX showed normal LV FS (n=84, mean z-score, 0.19, P=0.51) & contractility (n=22, mean z-score, -0.02, P=0.96); but slight LV dilation (n=79, dimension z-score, 0.28, P=0.03). After DOX, FS (n=91, mean z-score, -1.06, P<0.0001) & contractility (n=29, mean z-score, −0.82, P=0.02) were depressed & dimension was normal (n=89, mean z-score, 0.01, P=0.92). However, there were no significant differences between the DOX-alone & DEX-DOX pts for mean LV dimension, FS, or contractility before, during, or after DOX. FS was significantly depressed in both treatment groups during & after DOX. Conclusion: Echo-determined LV structure & function during therapy for ALL may not accurately assess myocardial injury measured by cTnT. The role of echo monitoring during therapy requires further study. Transient confounders (e.g., cytokine-mediated myocardial depressant substances) may misrepresent DOX-associated myocardial injury. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron NCI; Pharmacia-Upjohn, Inc.; Roche Diagnostocs Corp.