Abstract
Background:
Patients with acute myeloid leukemia (AML) are surviving longer. There is no data on changes in myocardial mechanics from standard of care low-dose anthracycline-based induction chemotherapy in older patients with AML. The aim of this study was to demonstrate the potential utility of strain imaging in detecting early changes in left ventricular function in this patient population after induction chemotherapy.
Methods:
32 patients enrolled in the ECOG-ACRIN E2906 study (cytarabine and daunorubicin vs. clofarabine [Genzyme/Sanofi]) from 2011 to 2014 were evaluated retrospectively. Two-dimensional transthoracic echocardiography (TTE) imaging with Doppler and two-dimensional speckle-tracking echocardiography (2DSTE) using EchoInsight software (Epsilon imaging) were performed before and after induction chemotherapy.
Results:
18 patients received cytarabine and daunorubicin (7+3) and 14 received clofarabine. The clofarabine group was older than the 7+3 cohort (67.8 ± 4.0 vs. 63.7 ± 3.8, p =0.007). There were no other significant differences in cardiac risk factors between groups. The 7+3 group had a decrease in average peak systolic global longitudinal (−19.1 ± 2.8 to −17.2 ± 3.0, p = 0.01) and circumferential strain (−29.4 ± 6.3 to −23.9 ± 4.3, p = 0.011). These changes were not demonstrated in the clofarabine group and were not associated with a decline in left ventricular ejection fraction (LVEF).
Conclusions:
In older AML patients, standard cytarabine and daunorubicin chemotherapy causes early changes in global longitudinal and circumferential strain not seen with clofarabine therapy. These findings demonstrate subclinical left ventricular dysfunction after exposure to low cumulative doses of anthracycline-based induction chemotherapy and may help us better identify those patients at risk for adverse long-term cardiovascular outcomes.
Keywords: Anthracyclines, Cardiotoxicity, Left ventricular function, Acute Myeloid Leukemia, Two-dimensional speckle-tracking strain
Introduction
Anthracyclines are well-established, effective chemotherapeutic agents in the treatment of both solid and hematologic malignancies and have been the mainstay of induction chemotherapy in acute myeloid leukemia (AML) for over 40 years [1, 2]. Although the overall incidence of leukemia is increasing nationwide, leukemia mortality has declined in recent years, creating a larger number of leukemia survivors [3]. It is estimated that there will be 19,520 new cases of AML and 8,850 survivors of AML in the United States in 2018 [4]. AML is also generally a disease of older adults with an average age in the mid-sixties[4]. Therefore, survivors also carry increased cardiovascular co-morbidities and may be at higher risk for treatment-related side effects. Anthracyclines cause a variety of cardiotoxic effects, including electrocardiographic changes, arrhythmia, conduction abnormalities, and left ventricular (LV) dysfunction [5]. The most common manifestation of anthracycline-induced cardiotoxicity (AIC) is a dose-dependent reduction in ejection fraction (EF) that can lead to heart failure [6]. The overall incidence of clinical heart failure due to anthracycline therapy is estimated to be between 2–5%, with higher rates being seen in patients treated for acute leukemia [7]. Recent studies [8] have identified cardiotoxicity at doxorubicin doses in the range of 100–150 mg/m2 can cause cardiotoxicity. This is much lower than had previously recognized in the past.
Clinical symptoms and reduction in EF are two of the parameters currently followed by oncologists in the surveillance of AIC. However, reduction in EF is a late manifestation [9]. Detection of subclinical changes in cardiac function may have important prognostic and therapeutic implications. Recovery in EF and a reduction of associated cardiac events can be achieved when LV dysfunction is detected early and cardioprotective therapy is promptly initiated [10]. Two-dimensional speckle-tracking echocardiography (2DSTE) is an advanced echocardiographic technique that is increasingly being used in the cancer population to detect subclinical changes in LV function from anticancer therapies. 2DSTE is an angle-independent technique that provides local displacement information from which components of myocardial mechanics, such as strain and strain rate, can be derived [11]. 2DSTE has demonstrated increased sensitivity in detecting early LV dysfunction in patients receiving anthracycline chemotherapy [12].
The risk of cardiotoxicity in older patients with AML receiving standard of care anthracycline-based induction chemotherapy is not well defined. This patient group also carries increased cardiovascular co-morbidities which sets them at a higher risk for cardiotoxicity. As survivorship is increasing, more data is needed to better understand these cardiovascular risks in patients with AML. The aim of this study was to use 2DSTE to evaluate the cardiac effects of low dose anthracycline chemotherapy in older patients with AML who were treated on a phase III randomized clinical trial comparing standard of care 7+3 chemotherapy with daunorubicin and cytarabine to a non-anthracycline treatment regimen with clofarabine.
Material and Methods
Study Subjects
32 subjects were retrospectively included from two academic institutions, the Robert H. Lurie Comprehensive Cancer Center of Northwestern University (Chicago, IL) and the Abramson Cancer Center at the University of Pennsylvania (Philadelphia, Pennsylvania), who enrolled subjects in the ECOG-ACRIN E2906 Trial, Phase III Randomized Trial of Clofarabine as Induction and Post-Remission Therapy vs. Standard Daunorubicin & Cytarabine Induction and Intermediate Dose Cytarabine Post-Remission Therapy, Followed by Decitabine Maintenance vs. Observation in Newly-Diagnosed Acute Myeloid Leukemia in Older Adults (Age>/=60 Years) from 2011 – 2014. The study was approved by the institutional review board at each institution. All patients were over the age of 60 with newly diagnosed AML and considered candidates for chemotherapy based on examination of peripheral blood or bone marrow aspirate specimens. Patients were randomized to receive clofarabine [Genzyme/Sanofi] as induction and post-remission therapy versus standard cytarabine and daunorubicin (7+3) induction and intermediate dose cytarabine post-remission therapy. Patients at these two institutions received a baseline and a post-treatment echocardiogram within 1.5 months of completion of induction chemotherapy.
Demographic identifiers included age, ethnicity, and gender. Clinical comorbidities included body mass index (BMI), hypertension, diabetes, coronary artery disease, hyperlipidemia, cumulative anthracycline dosage, prior mediastinal radiation, and the use of cardioprotective medications at time of chemotherapy (specifically, angiotensin converting enzyme inhibitors [ACE-i] or angiotensin receptor blockers (ARB) and beta-blockers). Quantitative values extracted from the chart included systolic/diastolic blood pressure and heart rate, recorded at time of hospital admission. Cardiac biomarkers were not included in the oncology protocol and thus were not obtained at the time of chemotherapy. Patients receiving induction chemotherapy with the standard 7+3 regimen received cytarabine 100 mg/m2 for seven consecutive days plus daunorubicin 60 mg/m2 (doxorubicin equivalent: 50 mg/m2) for three consecutive days. The cumulative dose of daunorubicin was 180 mg/m2 (doxorubicin equivalent: 150 mg/m2). Patients randomized to the non-anthracycline clofarabine treatment arm received clofarabine 50 mg/m2 for five consecutive days. Demographic data of the studied population is included in Table 1.
Table 1.
Clinical Characteristics of AML Patients Receiving Cytarabine/Daunorubicin (7+3) versus Clofarabine
| Clinical Characteristics (n=23) |
7+3 n (%) or Mean Value ± SD (n=14) |
Clofarabine n (%) or Mean Value ± SD (n=9) |
P-value |
|---|---|---|---|
| Age (years) | 63.7 ± 3.8 | 67.8 ± 4.0 | 0.007 |
| Gender (male) | 8 (44%) | 8 (57%) | 0.476 |
| Non-White | 1 (7%) | 1 (6%) | 0.356 |
| Hypertension | 9 (50%) | 7 (50%) | 0.639 |
| Diabetes Mellitus | 5 (28%) | 3 (21%) | 0.681 |
| Hyperlipidemia | 6 (33%) | 6 (43%) | 0.581 |
| Coronary Artery Disease | 0 (0%) | 2 (14%) | 0.098 |
| Current / Former Smoker | 8 (44%) | 8 (57%) | 0.476 |
| Prior Anthracycline/Trastuzumab | 0 (0%) | 0 (0%) | 1.00 |
| Prior Mediastinal Radiation | 2 (11%) | 0 (0%) | 0.198 |
| ACE-I / ARB | 5 (28%) | 5 (36%) | 0.631 |
| Beta-blocker | 3 (17%) | 6 (43%) | 0.102 |
| Cumulative Anthracycline Dose (mg/m2) | 180.0 | 0.00 | 0.00 |
| Systolic Blood Pressure (mm Hg) | 125.4 ±13.4 | 115.6 ± 12.3 | 0.204 |
| Diastolic Blood Pressure (mm Hg) | 67.9 ± 11.6 | 58.3 ± 9.2 | 0.031 |
| Heart Rate (beats per minute) | 84.3 ±12.6 | 76.9 ± 13.06 | 0.234 |
Transthoracic Echocardiography
Transthoracic echocardiography (TTE) images were acquired prior to the initiation of chemotherapy and after completion of chemotherapy (mean 44.0 days for 7+3 group and 54.0 days for clofarabine group) (Figure 1). Of the 32 patients enrolled in the trial, nine patients were excluded from analysis. Four patients had multigated acquisition scan (MUGA) performed instead of TTE, two patients did not have post-treatment TTE at the time of data acquisition, and three patients did not have all of the necessary views obtained to complete speckle-tracking analysis. The remainder of echocardiographic data was included in final data analysis. All echocardiograms included in final data analysis were performed on patients in normal sinus rhythm. All transthoracic images were retrospectively reviewed and interpreted by two study investigators in a blinded fashion.
Figure 1.
Study participants and timeline of echocardiography.
Conventional Echo-Doppler and Tissue Doppler Imaging (TDI) Measurements
Conventional echocardiographic examination consisted of M-mode, two-dimensional (2-D), pulsed and continuous wave Doppler velocity. M-mode was used for measurement of tricuspid annular systolic excursion (TAPSE). 2-D imaging was used for measurement of left ventricular internal diameter at end-diastole (LVIDd), left ventricular posterior wall thickness (LVPW), and left atrial (LA) volume from the area-length method using the apical four-chamber and apical two-chamber views at ventricular end systole. 2-D imaging was also used to measure the right ventricular (RV) basal diameter at the tricuspid annulus at end-diastole, LVEF was determined by performing Simpson’s biplane measurement using apical two-chamber and four chamber views at end-systole and end-diastole. Doppler was used to determine peak E and peak A wave velocities, the E/A ratio, and deceleration time (DT) for the mitral valve. EF was determined by performing Simpson’s biplane measurement from TTE images [16]. Pulsed wave tissue Doppler imaging (TDI) measures included systolic (s’) and diastolic (e’, a’) myocardial velocities at the basal segments of the LV septal and lateral walls. Conventional 2D, Doppler and TDI echocardiographic values are summarized in Table 2.
Table 2.
Conventional 2D and TDI echocardiographic measurements by treatment group
| Echocardiographic parameter | Treatment Group | Pre-Treatment (± SD) | Post-Treatment (± SD) | P-value |
|---|---|---|---|---|
| LVIDd indexed cm/m2 | Clofarabine | 2.28 (±0.28) | 2.26 (±0.23) | 0.74 |
| LVEF (Simpson’s biplane) | Clofarabine | 0.64 (±0.06) | 0.58 (±0.08) | 0.19 |
| Mitral E wave velocity cm/s | Clofarabine | 82.52 (±19.12) | 80.50 (±23.19) | 0.74 |
| Mitral A wave velocity cm/s | Clofarabine | 79.29 (±16.52) | 85.83 (±21.37) | 0.07 |
| E/A | Clofarabine | 1.06 (±0.25) | 0.95 (±0.20) | 0.55 |
| Deceleration time ms | Clofarabine | 243 (±153.8) | 230 (±45.2) | 0.55 |
| Mitral Septal s’ wave velocity cm/s | Clofarabine | 8.66 (±1.32) | 9.6 (±3.37) | 0.64 |
| Mitral Septal e’ wave velocity cm/s | Clofarabine | 9.01 (±2.44) | 7.8 (±2.93) | 0.58 |
| Mitral Septal a’ wave velocity cm/s | Clofarabine | 11.05 (±1.50) | 12.12 (±4.19) | 0.44 |
| Mitral Lateral s’ wave velocity cm/s | Clofarabine | 9.17 (±1.88) | 9.17 (±2.49) | 0.44 |
| Mitral Lateral e’ wave velocity cm/s | Clofarabine | 10.93 (±2.04) | 9.46 (±2.49) | 0.41 |
| Mitral Lateral a’ wave velocity cm/s | Clofarabine | 12.36 (±2.36) | 11.38 (±1.91) | 0.33 |
| RV basal diameter | Clofarabine | 2.97 (±0.47) | 2.94 (±0.69) | 0.55 |
| TAPSE | Clofarabine | 2.23 (±0.45) | 2.14 (±0.21) | 0.54 |
Two-Dimensional Speckle-Tracking Echocardiography
Left ventricular 2DSTE was performed by manual tracing by two investigators using a vender neutral commercial software (EchoInsight software by Epsilon Imaging). Nonforeshortened 2D apical 2-chamber, 3-chamber and 4-chamber views were identified for calculation of average global peak systolic longitudinal strain. The mid papillary parasternal short axis view was used for calculation of circumferential strain. With this software, frame rates 30 – 60 frames per second were used. Bull’s Eye comparisons of GLS pre- and post- treatment were reviewed for each patient (Figure 2). No patients were excluded from the study due to suboptimal windows. 2DSTE values for each treatment group are summarized in Table 3.
Figure 2.
Pre- and post- “Bull’s Eye” plots of a patient receiving cytarabine and daunorubicin demonstrating a strain-detected myocardial injury pattern.
Table 3.
Strain Values by Treatment Group
| 2D-STE Values | Treatment Group | Pre-Treatment (± SD) | Post-Treatment (± SD) | P-value |
|---|---|---|---|---|
| Average Global Longitudinal Strain (%) | Clofarabine | 17.9 ± 3.3 | −18.2 ± 2.7 | 0.68 |
| Two-chamber Longitudinal Strain (%) | Clofarabine | −18.3 ± 3.3 | −17.6 ± 1.7 | 0.34 |
| Three-chamber Longitudinal Strain (%) | Clofarabine | −16.8 ± 5.5 | −17.7 ± 4.2 | 0.60 |
| Four-chamber Longitudinal Strain (%) | Clofarabine | −18.0 ± 3.2 | −19.3 ± 4.2 | 0.31 |
| Circumferential Strain (%) | Clofarabine | −26.1 ± 8.5 | −26.6 ± 7.6 | 0.82 |
Reproducibility Analysis
Inter- and intra-rater reproducibility was assessed in 11 randomly selected patients by two investigators in a blinded fashion (Table 4).
Table 4.
Inter- and Intra-Rater Reliability
| Parameter | Inter-class correlation [CI] | Intra-class correlation [CI] |
|---|---|---|
| Two-chamber Longitudinal Strain | 0.66 (0.31–1.00) | 0.65 (0.30–1.00) |
| Three-chamber Longitudinal Strain | 0.57 (0.16–0.98) | 0.50 (0.05–0.95) |
| Four-Chamber Longitudinal Strain | 0.91 (0.80–1.00) | 0.88 (0.75–1.00) |
| Circumferential Strain | 0.84 (0.66–1.00) | 0.80 (0.58–1.00) |
| Global Longitudinal Strain | 0.81 (0.60–1.00) | 0.80 (0.57–1.00) |
Statistical Analysis
Statistical analysis was performed using Statistical Analysis System (SAS Institute Inc. 2012. SAS OnlineDoc® 9.4. Cary, NC: SAS Institute Inc.). The lead author had full access to all of the data in the study. Continuous values were expressed as mean +/− standard deviation. Categorical data were expressed as percentages. Chi-square or t-testing was performed, when appropriate, with p < 0.05 indicating statistical significance. Inter-rater reproducibility was assessed using two statistics, the intra-class correlation coefficient and Lin’s concordance coefficient. For each method, the coefficient and 95% confidence interval were calculated in 11 randomly selected patients by two examiners who were blinded.
Results
Patient Characteristics
Of the 32 patients included in the study, 18 received the standard regimen (cytarabine and daunorubicin, or “7+3”) while 14 received the novel agent, clofarabine. The demographic data of the studied population is included in Table 1.
LV Function Pre- and Post-Chemotherapy
Conventional 2D, Doppler and TDI echocardiographic values are summarized below (Table 2). LVEF by Simpson’s method decreased in both groups after chemotherapy, but did not meet statistical significance. Mitral inflow parameters showed a statistically significant decrease in mitral E wave velocity (90.65 ± 21.87 to 77.20 ± 15.92, p = 0.015) in the 7+3 group which was not demonstrated in the clofarabine group. TDI was notable for a statistically significant decrease in mitral septal e’ (7.91 ± 1.73 to 6.34 ± 1.45, p= 0.002) and approached statistical significance in mitral septal s’ (9.24 ± 2.74 to 6.94 ± 1.42, p = 0.051) in the 7+3 cohort, which was not demonstrated in the clofarabine group. 2DSTE values for each treatment arm can be seen in Table 3. The 7+3 treatment arm had a statistically significant decrease in longitudinal strain in the apical two-chamber (−19.6% ± 2.7 to −17.5% ± 2.7, p = 0.015) and apical three-chamber (−19.5% ± 4.4 to −16.1 ± 2.9, p = 0.011) views, as well as in global longitudinal strain (−19.1% ± 2.8 to −17.2 ± 3.0, p = 0.010) and circumferential strain (−29.4% ± 6.3 to −23.9 ± 4.3, p = 0.011). The changes in global longitudinal strain pre- and post-treatment in the two arms are shown in Figures 2 and 3. No statistically significant changes in strain values were seen in the clofarabine treatment arm. EF remained within normal limits in both treatment arms, and there was no statistically significant difference in EF pre- and post-therapy in either group of patients.
Figure 3A.
Pre- and post-treatment APSGLS in 7+3 group.
Discussion
This is the first study using 2DSTE to evaluate changes in myocardial mechanics in older patients with AML treated with standard low doses of anthracycline chemotherapy (cytarabine and daunorubicin, or “7+3”) compared to a novel non-anthracycline chemotherapy (clofarabine) in a longitudinal, randomized design.
The demographic and clinical characteristics were similar between the two treatment groups. The cohort of patients treated with clofarabine was noted to be older than the 7+3 group. Additionally, the 7+3 group was noted to have higher mean diastolic blood pressure compared to the clofarabine group. Despite these differences, traditional heart disease risk factors, including clinical diagnosis of hypertension, hyperlipidemia, diabetes mellitus, or active/past tobacco use were similar between the two groups. The use of cardioprotective agents, defined as active use of beta-blocker, ACE-i or ARB at the time of chemotherapy, was also similar between the two groups. None of the patients in the study had prior exposure to anthracyclines or trastuzumab.
EF was preserved in both treatment arms, and there was no statistically significant change in EF demonstrated in either group after completion of therapy. Despite receiving low cumulative doses of daunorubicin (180 mg/m2, 150 mg/m2 doxorubicin equivalent), the 7+3 cohort was noted to have a statistically significant decrease in global longitudinal strain and circumferential strain compared to the clofarabine treatment arm. This impairment in LV systolic function is further corroborated by tissue Doppler interrogation, which demonstrated a significant decrease in mitral septal s’ in the 7+3 cohort. There was also a reduction in mitral septal e’ in the 7+3 cohort that suggests an impairment in diastolic function. Similar tissue Doppler-derived findings have been demonstrated in pediatric patients receiving induction chemotherapy for acute hematologic malignancies [13]. Interestingly, 5 of the 18 individuals in the 7+3 group had little change or slight improvement in GLS after anthracycline therapy. There were no significant differences in clinical descriptors, age, anthracycline dose, or use of cardioprotective agents in this group compared to the remainder of the 7+3 cohort. Although this could be reflective of a small sample size and variability in measurement, this finding certainly merits further exploration in a larger cohort to determine if there are any patient-specific protective factors.
Previously, the risk for cardiotoxicity after treatment with an anthracycline was thought to be significant at only higher doses. However, data is emerging that there is no safe dose of anthracyclines. A study by Blanco and colleagues [8] found an odds ratio of 3.85 for the development of cardiomyopathy with doxorubicin doses in the range of 100–150 mg/m2. Jordan et al demonstrated early changes in cardiac magnetic resonance as measured by T1-weighted signal intensity in patients treated with low dose anthracycline, with a median dose of doxorubicin of 240 mg/m2[14]. In our study, we observed early changes in cardiac function as measured by global longitudinal strain and circumferential strain, at a doxorubicin equivalent of 150 mg/m2.
AIC is thought to represent a disease continuum, with early impairment of myocardial contractility preceding a decrease in EF or clinical symptoms of heart failure in a dose-dependent fashion. The long-axis function of the left ventricle is governed by subendocardial, longitudinally-oriented myocardial fibers, which are more susceptible to early hypoxia and myocardial injury due to anthracycline exposure [13]. In the setting of early myocardial injury, circumferential strain may initially play a compensatory role and preserve left ventricular function. Over time, though, circumferential strain can be affected as the disease progresses and may indicate transmural involvement [15]. Because of this, it has been hypothesized that abnormal circumferential strain may be predictive of long-term outcomes. Our study demonstrated statistically significant changes in both longitudinal and circumferential strain in AML patients treated with 7+3 chemotherapy. Long-term, prospective data would be helpful in determining the prognostic value of these changes.
Because of its sensitivity in detecting early myocardial injury, the prognostic import of strain is an emerging concept in cardio-oncology literature. Sawaya et al [16] prospectively followed 81 women with HER2+ breast cancer treated with anthracyclines for three months, followed by weekly paclitaxel and trastuzumab for three months, and trastuzumab every three weeks for nine additional months. Echocardiograms were obtained at baseline, after anthracycline treatment and every three months on trastuzumab. 32% of patients developed cardiotoxicity. Peak systolic longitudinal myocardial strain measured at completion of anthracycline chemotherapy was predictive of the later development of cardiotoxicity. In a long-term prospective study over 1.9 years in breast cancer patients treated with doxorubicin and/or trastuzumab therapy, circumferential strain was strongly predictive of chemotherapy related cardiac dysfunction [17].
There is a paucity of data in the literature regarding the clinical utility of myocardial strain in adult patients with hematologic malignancies. One recent study [7] evaluated prechemotherapy echocardiography in individuals with leukemia and lymphoma treated with anthracyclines. This group found abnormal prechemotherapy GLS independently associated with cardiac events, defined as symptomatic heart failure or cardiac death, even after controlling for clinical variables. In fact, GLS less than the absolute value of 17.5% was associated with a six-fold increase in cardiac events. Another study [3] compared strain parameters in patients with acute leukemia versus those without cancer, or those with a different type of malignancy. Patients with acute leukemia had higher LV volumes and lower GLS than patients without cancer and lower GLS than patients with breast cancer. It was theorized that acute leukemia may predispose to cardiac dysfunction because of high cytokine release or direct leukemic myocardial infiltration. Therefore, the type of cancer treated may play a role in the development of cardiotoxicity, aside from the anthracycline dose or traditional cardiovascular risk factors.
Long-term longitudinal data regarding changes in myocardial strain after anthracycline therapy in older adult leukemic patients does not exist. A recent study [18] evaluated comprehensive echocardiographic assessment, including strain imaging, in a large cohort of adult survivors of pediatric cancer. The prevalence of abnormal GLS and CS in patients previously exposed to anthracyclines only was found to be 26.6% and 23.3%, respectively.
Advanced age is associated with increase in coronary heart disease, stroke, hypertension, heart failure, and other cardiovascular disease [19]After the age of 60 years, American adults will have 1 or more cardiovascular co-morbidities and are more susceptible to coronary heart disease. As anthracyclines are given for curative intent in AML, understanding the cardiac side-effects and their impact on morbidity in AML survivors is increasingly important. The changes in strain demonstrated in our patient group are likely due to a combination of anthracycline exposure, increased cardiovascular co-morbidities, and perhaps with the cancer type itself in older adults.
Limitations
First, as a retrospective study, the acquisition of echocardiographic images was not standardized between the two institutions. Second, despite including studies from two institutions, it is also possible that our small sample size prevented detection of change in EF. Additionally, these patients were only followed for a short period of time after chemotherapy administration. A large, prospective study following these patients for a longer duration of time will be needed to determine if the changes in GLS have a meaningful impact on cardiovascular outcomes. Finally, it is unclear if the results of our study are specific to the older acute leukemia population or can be broadened to other malignancies treated with anthracycline therapy. Further evaluation is needed to determine if the older leukemia population itself is exquisitely prone to early strain changes compared to other cancer populations, as has been previously hypothesized [3].
Conclusions
The risk of cardiotoxicity in older patients with AML receiving standard of care anthracycline-based induction chemotherapy is not well defined. In this first pilot study of 2DSTE in older patients with AML who received standard anthracycline-based induction chemotherapy, we demonstrated that administration of low dose anthracycline chemotherapy (cumulative daunorubicin dose of 180 mg/m2) was associated with subclinical LV dysfunction. As survivorship improves in older patients with AML, identifying treatment-related subclinical LV dysfunction may help us better identify those at risk for adverse long-term cardiovascular outcomes.
Figure 3B.
Pre- and post-treatment APSGLS for clofarabine group.
Acknowledgments
This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: CA180820, CA180794, CA180790, CA180791. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.
Footnotes
Disclosures
Gregory J. Cascino: None
Woo Bin Vos: None
Jonathan Canaani: None
Nicholas Furiasse: None
Bonnie Ky: None
Selina M. Luger: None
Jessica K. Altman: None
James M. Foran: None
Martin S. Tallman: None
Mark R. Litzow: None
Vera Rigolin: None
Nausheen Akhter: None
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