scholarly journals Changes in Cardiac Biomarkers During Doxorubicin Treatment of Pediatric Patients With High-Risk Acute Lymphoblastic Leukemia: Associations With Long-Term Echocardiographic Outcomes

2012 ◽  
Vol 30 (10) ◽  
pp. 1042-1049 ◽  
Author(s):  
Steven E. Lipshultz ◽  
Tracie L. Miller ◽  
Rebecca E. Scully ◽  
Stuart R. Lipsitz ◽  
Nader Rifai ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Troponin T ◽  
Lymphoblastic Leukemia ◽  
Cardiac Injury ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Inflammatory Biomarker ◽  
Doxorubicin Group

Purpose Doxorubicin causes cardiac injury and cardiomyopathy in children with acute lymphoblastic leukemia (ALL). Measuring biomarkers during therapy might help individualize treatment by immediately identifying cardiac injury and cardiomyopathy. Patients and Methods Children with high-risk ALL were randomly assigned to receive doxorubicin alone (n = 100; 75 analyzed) or doxorubicin with dexrazoxane (n = 105; 81 analyzed). Echocardiograms and serial serum measurements of cardiac troponin T (cTnT; cardiac injury biomarker), N-terminal pro-brain natriuretic peptide (NT-proBNP; cardiomyopathy biomarker), and high-sensitivity C-reactive protein (hsCRP; inflammatory biomarker) were obtained before, during, and after treatment. Results cTnT levels were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before treatment but in 47% and 13%, respectively, after treatment (P = .005). NT-proBNP levels were increased in 89% of children in the doxorubicin group and in 92% of children in the doxorubicin-dexrazoxane group before treatment but in only 48% and 20%, respectively, after treatment (P = .07). The percentage of children with increased hsCRP levels did not differ between groups at any time. In the first 90 days of treatment, detectable increases in cTnT were associated with abnormally reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness 4 years later (P < .01); increases in NT-proBNP were related to an abnormal LV thickness-to-dimension ratio, suggesting LV remodeling, 4 years later (P = .01). Increases in hsCRP were not associated with any echocardiographic variables. Conclusion cTnT and NT-proBNP may hold promise as biomarkers of cardiotoxicity in children with high-risk ALL. Definitive validation studies are required to fully establish their range of clinical utility.

Abstract 6073: Dexrazoxane Cardioprotection in Doxorubicin-Treated Children with Acute Lymphoblastic Leukemia: Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocol 95–01 Randomized Controlled Trial

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Steven E Lipshultz ◽  
Rebecca E Scully ◽  
Stuart R Lipsitz ◽  
Stephen E Sallan ◽  
Lewis B Silverman ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Post Treatment ◽  
Lv Function ◽  
Z Score ◽  
Childhood All ◽  
Dana Farber Cancer Institute

Background: Doxorubicin (DOX) chemotherapy injures myocardial cells, leading to progressive cardiac dysfunction. Dexrazoxane (DZR), a free-radical scavenger, reduced troponin T (cTnT) elevation during therapy in children with acute lymphoblastic leukemia (ALL) on Dana-Farber Cancer Institute (DFCI) Protocol 95– 01. The long-term cardiac benefits of DZR are not yet known. Methods: We centrally remeasured echocardiograms from childhood ALL survivors who were randomly assigned to DOX (n =64; 30 mg/m 2 /dose for 10 doses) with or without DZR (n =58; 300 mg/m 2 /dose) during DFCI Protocol 95– 01. Results: Demographics and follow-up were similar in both arms (median f/u years: DOX 4.0 vs. DZR/DOX 3.7). Mean left ventricular (LV) end-systolic dimension was significantly abnormal for DOX vs. DZR/DOX at 3 years (mean Z-score: DOX 0.637 vs. DZR/DOX −0.0005, P=0.0164) and progressed at 3.5 years (0.800 vs. −0.006, P=0.0028) and 4 years (1.01 vs. 0.005, P=0.0013). DOX-group mean LV end-diastolic (ED) dimension was significantly dilated at 3.5 years (mean Z-score: DOX 0.223 vs. DZR/DOX −0.424, P=0.022) and 4 years (0.428 vs. −0.456, P=0.004). With 3.5 years follow-up, a number of non-significant trends showed DZR/DOX echo measures to be more normal: LV fractional shortening Z-score (DOX −2.092 vs. DZR/DOX −1.00); LV mass Z-score (−0.672 vs. −0.537); LVED posterior wall thickness Z-score (LVEDPWTz; −0.596 vs. −0.395). For DZR/DOX-patients, cTnT elevation (defined as >0.01 ng/ml) during DOX treatment correlated with thinner LVED posterior wall 3.5 years post treatment (mean LVEDPWTz: cTnT− =−0.011 vs. cTnT+= −1.200, P=0.0352). Conclusions: DZR is protective against late DOX cardiotoxicity with smaller LV dimensions, consistent with less LV remodeling. LV function, thickness, and mass trended to more normal among children who received DZR and all parameters trended toward a greater DZR effect over time. Further, cTnT elevation during therapy predicted late LV wall thinning. Table 1: Post-treatment Mean Differences in Dimension Z-Scores

scholarly journals Troponin-I and left ventricular function in pediatric high-risk acute lymphoblastic leukemia after daunorubicin treatment

2021 ◽  
Vol 61 (2) ◽  
pp. 107-14
Author(s):  
Rinche Annur ◽  
Didiko Hariyant ◽  
Amirah Zatil Izzah
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Troponin I ◽  
Systolic Function ◽  
Lymphoblastic Leukemia ◽  
Left Ventricular Systolic Function ◽  
Significant Negative Correlation ◽  
Left Ventricular ◽  
Ventricular Systolic Function ◽  
Echocardiographic Parameters

Background Daunorubicin is a chemotherapy drug for leukemia treatment, but it can cause cardiotoxicity. When heart damage occurs, myocardial sarcomeres release troponin-I, which could potentially be useful as a cardiotoxicity biomarker. Objective To assess for possible correlations between troponin-I and echocardiographic parameters of left ventricular function after administration of daunorubicin in children with high-risk acute lymphoblastic leukemia (ALL). Methods This cross-sectional study on 37 children with high-risk ALL was performed from July 2017 to December 2018, in Padang, West Sumatera. The left ventricular systolic function parameters measured were ejection fraction (EF) and fractional shortening (FS); the left ventricular diastolic function parameter was E/A ratio. Troponin-I measurements and echocardiography were performed after daunorubicin treatment at the end of induction phase chemotherapy. Pearson’s correlation test was used to analyze for a correlation between troponin-I and echocardiographic parameters. Results Subjects had a mean age of 6.27 (SD 4.43) years, and males comprised 56.8%. Subjects’ mean troponin-I concentration was 5.49 (SD 0.86) ng/mL, and mean EF, FS, and E/A values were 65 (SD 5) %, 36 (SD 4) %, and 1.52 (SD 0.56), respectively. Troponin-I was not significantly correlated with EF (r=0.062; P=0.715) or FS (r=0.309; P=0.172). However, there was a weak, significant negative correlation between troponin-I and E/A ratio (r=-0.383; P=0.019). Conclusion Troponin-I level has no significant correlations with the echocardiographic parameters of left ventricular systolic function.  However, there is a weak significant negative correlation between troponin-I level and the left ventricular diastolic parameter of E/A ratio.    

scholarly journals ECG Scoring for the Evaluation of Therapy-Naïve Cancer Patients to Predict Cardiotoxicity

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1197
Author(s):  
Julia Pohl ◽  
Raluca-Ileana Mincu ◽  
Simone M. Mrotzek ◽  
Reza Wakili ◽  
Amir A. Mahabadi ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Cancer Therapies ◽  
University Hospitals ◽  
Anti Cancer ◽  
Risk Patients ◽  
Qrs Duration ◽  
Ecg Score

Objective: To evaluate a new electrocardiographic (ECG) score reflecting domains of electrical and structural alterations in therapy-naïve cancer patients to assess their risk of cardiotoxicity. Methods: We performed a retrospective analysis of 134 therapy-naïve consecutive cancer patients in our two university hospitals concerning four ECG score parameters: Contiguous Q-waves, markers of left ventricular (LV) hypertrophy, QRS duration and JTc prolongation. Cardiotoxicity was assessed after a short-term follow-up (up to 12 months). Results: Of all the patients (n = 25), 19% reached 0 points, 50% (n = 67) reached 1 point, 25% (n = 33) reached 2 points, 5% (n = 7) reached 3 points and 0.7% reached 4 or 5 points (n = 1 respectively). The incidence of cardiotoxicity (n = 28 [21%]) increased with the ECG score, with 0 points at 0%, 1 point 7.5%, 2 points 55%, 3 points 71% and ≥3 points 50%. In the ROC (Receiver operating curves) analysis, the best cut-off for predicting cardiotoxicity was an ECG score of ≥2 points (sensitivity 82%, specificity 82%, AUC 0.84, 95% CI 0.77–0.92, p < 0.0001) which was then defined as a high-risk score. High-risk patients did not differ concerning their age, LV ejection fraction, classical cardiovascular risk factors or cardiac biomarkers compared to those with a low-risk ECG score. Conclusion: ECG scoring prior to the start of anti-cancer therapies may help to identify therapy-naïve cancer patients at a higher risk for the development of cardiotoxicity.

scholarly journals Genetic Alterations Activating Kinase and Cytokine Receptor Signaling in High-Risk Acute Lymphoblastic Leukemia

Cancer Cell ◽  
2012 ◽  
Vol 22 (2) ◽  
pp. 153-166 ◽  
Author(s):  
Kathryn G. Roberts ◽  
Ryan D. Morin ◽  
Jinghui Zhang ◽  
Martin Hirst ◽  
Yongjun Zhao ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Cytokine Receptor ◽  
Receptor Signaling
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