Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma.

Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase 2 investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients ≥18 years of age with untreated, early, unfavorable, or advanced-stage disease were eligible for treatment. Thirty patients (early unfavorable stage, n = 12; advanced stage, n = 18) were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4 to 6 cycles, depending on stage and bulk. Twelve had either large mediastinal masses or bulky disease (>10 cm). After pembrolizumab monotherapy, 11 patients (37%) demonstrated CMRs, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography computed tomography scans had >90% reduction in metabolic tumor volume. All patients achieved CMR after 2 cycles of AVD and maintained their responses at the end of treatment. With a median follow-up of 22.5 months (range, 14.2-30.6) there were no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well tolerated. The most common immune-related adverse events were grade 1 rash (n = 6) and grade 2 infusion reactions (n = 4). One patient had reversible grade 4 transaminitis and a second had reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD was both highly effective and safe in patients with newly diagnosed cHL, including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.

Postsurgical hemodynamics of the aortic valve bypass operation evaluated with phase contrast magnetic resonance.

PURPOSE: To characterize the postsurgical hemodynamics in aortic valve bypass (AVB) patients, and to determine the relationship between presurgical native aortic valve pressure gradient and postsurgical hemodynamics. MATERIALS AND METHODS: Twenty patients scheduled for AVB surgery underwent presurgical transthoracic Doppler echocardiography to assess the degree of aortic stenosis and postsurgical cardiac magnetic resonance imaging (MRI) to acquire phase contrast magnetic resonance (PCMR) flow values along the ascending and descending aorta, and in the conduit. Net flow values were calculated from the PCMR images and compared to presurgical aortic valve pressure gradient measurements. RESULTS: PCMR showed that: 1) The blood flow split between the aorta and the conduit was 35%:65% of cardiac output and 2) 60% of patients had net retrograde blood flow in the superior thoracic aorta over the cardiac cycle. Patients with presurgical pressure gradient (ΔP) > 45 mmHg had significantly less blood flow out of the native aorta than patients with ΔP < 45 mmHg, and had significantly more retrograde flow in the superior thoracic aorta postsurgery. CONCLUSION: In patients undergoing AVB, presurgical aortic valve pressure gradient is associated with the volume of blood flow out the aorta and the direction of blood flow in the superior thoracic aorta after conduit addition as measured by PCMR.

Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma.

In a multicenter, phase 2, investigator-initiated trial of sequential pembrolizumab and AVD (doxorubicin, vinblastine, and dacarbazine), nearly two-thirds of patients with untreated, unfavorable, or advanced-stage classic Hodgkin lymphoma (cHL) achieved positron emission tomography (PET)-defined, complete or near-complete metabolic responses (CMRs), following pembrolizumab monotherapy. Furthermore, all patients achieved CMR after 2 cycles of AVD, with 100% of patients alive and without relapse at initial publication. We now report long-term follow-up, including the 3-year overall survival (OS) and planned correlative analyses. Thirty patients received 3 cycles of single-agent pembrolizumab, followed by AVD chemotherapy for 4 to 6 cycles depending on the stage and bulk. PET/computed tomography scan was performed after pembrolizumab monotherapy, 2 cycles of AVD, and at the end of therapy. Baseline biopsy samples were analyzed for genomic alterations of chromosome 9p24.1 and programmed cell death protein 1 (PD-1) pathway markers. At a median follow-up of 33.1 months (range, 26.0-43.0), progression-free survival and OS remained 100%. All patients had genomic alterations in 9p24.1 and were positive for programmed death ligand 1 (PD-L1) by immunohistochemistry. There was no relationship between depth of response to single-agent pembrolizumab and 9p24.1 alterations or PD-1 pathway H-scores. After additional follow-up, sequential pembrolizumab and AVD remained highly effective. The high response rates observed at all PD-L1 levels suggest that even low levels of PD-L1 expression are sufficient for response to PD-1 blockade in untreated cHL. An international phase 2 trial (registered at www.clinicaltrials.gov as #NCT03226249) is ongoing to confirm our findings.

Time-resolved analysis of coronary vein motion and cross-sectional area.

PURPOSE: To quantify periods of low motion and cross-sectional area changes of the coronary veins during the cardiac cycle for planning magnetic resonance coronary venograms (MRCV). MATERIALS AND METHODS: Images were acquired from 19 patients with coronary artery disease (CAD) and 13 patients scheduled for cardiac resynchronization therapy (CRT). The displacement and cross-sectional area of the coronary sinus was tracked, and periods of low motion were defined as consecutive time points during which the position of the coronary sinus remained within a 0.67-mm diameter region. Patients were classified as systolic dominant or diastolic dominant based on the relative duration of their low motion periods. RESULTS: All CRT patients were classified as systolic dominant, and 32% of these had no separate diastolic rest period. All CAD patients with ejection fraction < 35% were classified as systolic dominant, while all CAD patients with ejection fraction > 35%were diastolic dominant. In 77% of all subjects, the cross-sectional area of the coronary sinus was larger in systole than in diastole. CONCLUSION: The movement of the coronary sinus can be used to classify patients as either having a longer systolic or diastolic rest period. The classification of the CRT patients as systolic dominant suggests that MRCVs be acquired in systole for CRT planning; however, each patient's low motion periods should be categorized to ensure the correct period is being used to minimize motion artifacts.

Three-directional myocardial phase-contrast tissue velocity MR imaging with navigator-echo gating: in vivo and in vitro study.

The study protocol was HIPAA compliant and institutional review board approved. Informed consent was obtained from all participants. The purpose of the study was to prospectively validate the capability of navigator-echo-gated phase-contrast magnetic resonance (MR) imaging for measurement of myocardial velocities in a phantom and to prospectively use the phase-contrast MR sequence to measure three-directional velocity in the myocardium in vivo in volunteers and in patients scheduled for cardiac resynchronization therapy. An excellent correlation between the measured velocity and the true phantom motion (R = 0.90 for longitudinal velocity, R = 0.93 for circumferential velocity) was observed. Myocardial velocities were successfully measured in 17 healthy volunteers (11 male, six female; mean age, 27.5 years +/- 6.5 [standard deviation]) and 28 patients with heart failure (18 male, 10 female; mean age, 63.9 years +/- 15.0). Velocity values were significantly lower in the patients than in the volunteers. The time to peak velocity in the lateral wall of the patients, as compared with that in the volunteers, was delayed. Phase-contrast MR imaging can be combined with navigator-echo gating to measure three-directional myocardial tissue velocities in vivo.

Clinical and anatomic predictors of need for repeat atrial fibrillation ablation.

AIM: To identify predictors of need for repeat procedures after initial atrial fibrillation (AF) ablation. METHODS: We identified a cohort undergoing first time AF ablation at our institution from January 2004 to February 2014 who had cardiac magnetic resonance (CMR) imaging performed prior to ablation. Clinical variables and anatomic characteristics (determined from CMR) were assessed as predictors of need for repeat ablation. The decision regarding need for and timing of repeat ablation was at the discretion of the treating physician. RESULTS: From a cohort of 331 patients, 142 patients (43%) underwent repeat ablation at a mean of 13.6 ± 18.4 mo after the index procedure. Both male gender (81% vs 71%, P = 0.05) and lower ejection fraction (57.4% ± 10.3% vs 59.8% ± 9.4%, P = 0.04) were associated with need for repeat ablation. On pre-ablation CMR, mean pulmonary vein (PV) diameters were significantly larger in all four PVs among patients requiring repeat procedures. In multivariate analysis, increased right superior PV diameter significantly predicted need for repeat ablation (odds ratio 1.08 per millimeter increase in diameter, 95%CI: 1.00-1.16, P = 0.05). There were also trends toward significance for increased left and right inferior PV sizes among those requiring repeat procedures. CONCLUSION: Increased PV size predicts the need for repeat AF ablation, with each millimeter increase in PV diameter associated with an approximately 5%-10% increased risk of requiring repeat procedures.

Thromboembolism in cancer patients: pathogenesis and treatment.

In this review we summarize the causes of cancer related thrombosis as well as modern treatment approaches. Malignancy as a risk factor for thromboembolism is becoming increasingly recognized by clinicians caring for these patients. The probability of thrombosis occurring in an individual patient is dependent on several factors, including accompanying medical problems, the type of cancer, the clinical stage, performance status, and the treatment modalities employed. Thrombophilia with a history of thromboembolism is important as well. The overall risk of thrombosis is sevenfold that of noncancer patients. Though much has been learned about the pathogenesis of cancer-related thrombosis, we are in fact just beginning to understand the cross-talk between cancer cells and their related microenvironment, and such investigations are likely to increase our knowledge of cancer-related thrombosis mechanisms. Research in these areas may also suggest new strategies for cancer prevention, metastasis suppression, and new treatments. Drugs used in cancer therapy are increasingly recognized to directly contribute to the thrombotic tendency. Few studies provide data on the optimal management of cancer patients with thrombosis. It has been learned that retreating with the same drug can be very hazardous. In general the approach to prevention of thrombosis is the same as for noncancer patients, recognizing that specific cancer types and stage can place a patient in a high-risk category. Initial coumadin therapy fails in a significant number of patients with cancer. Recognition of the cancer patients at highest risk for coumadin failure is challenging. Low-molecular-weight heparins appear to be more effective in such situations where coumadin is likely to fail or has failed, but these drugs are thought to be costlier. Newer agents such as Factor Xa inhibitors and TF inhibitors are currently under investigation and may be found useful in the management of cancer-related thrombosis.

Pulmonary vein anatomy assessed by cardiac magnetic resonance imaging in patients undergoing initial atrial fibrillation ablation: implications for novel ablation technologies.

BACKGROUND: Novel atrial fibrillation (AF) ablation tools have been designed to facilitate "single-shot" pulmonary vein (PV) isolation using multi-electrode or balloon-based catheters. However, in contrast to point-by-point radiofrequency ablation, these tools may be more dependent on suitable PV anatomy to achieve circumferential PV isolation. METHODS: Three hundred and twenty-two patients underwent gadolinium-enhanced cardiac magnetic resonance angiography to delineate PV anatomy prior to initial AF ablation. Long (a) and short (b) axis measurements of the PV orifice were used to calculate the eccentricity index of the PV ostium. RESULTS: Long axis dimensions of the left superior PV were 18.2 ± 3.3 mm, left inferior PV 17.7 ± 3.9 mm, right superior PV (RSPV) 20.4 ± 4.3, and right inferior PV 18.7 ± 4.7 mm. The long axis dimension of the RSPV was significantly larger than other PVs (p < 0.001). Forty-two patients (13 %) had at least one PV with a long axis dimension >25 mm and 16 patients (5 %) had at least one PV with a long axis dimension >28 mm. Left-sided PV ostia were significantly more ellipse-shaped than the right-sided PVs, which tended to be more spherical. A significant positive correlation was noted between increasing PV size and increased orifice eccentricity. CONCLUSIONS: In this large cohort undergoing initial AF ablation, over 10 % of patients had at least one standard PV with a dimension >25 mm. Additionally, significant differences were noted between left- and right-sided veins with regard to orifice eccentricity. These findings have implications for the design of AF ablation tools and may account for differential isolation rates between PVs noted in some recent studies of novel ablation technologies.

Pulmonary Vein Remodeling Following Atrial Fibrillation Ablation: Implications For The Radiographic Diagnosis Of Pulmonary Vein Stenosis.

Background: Pulmonary vein (PV) reverse remodeling has been recognized following atrial fibrillation (AF) ablation. However, the extent of physiologic reverse remodeling after AF ablation and the potential impact of reverse remodeling on the radiographic diagnosis of PV stenosis have not been well characterized. Methods: From January 2004 to February 2014, 186 patients underwent paired cardiac magnetic resonance imaging (MRI) to delineate PV orifice dimensions before and after (mean 109 ± 61 days) an initial AF ablation. Results: Negative remodeling of the PV orifice cross sectional area occurred in 67.8% of veins with a mean reduction in area of 21.0 ± 14.1%, and positive remodeling was seen in the remaining PVs with an increase in area of 22.1 ± 23.4% compared to baseline. No PVs demonstrated a reduction in cross-sectional area of > 75% (maximum reduction observed was 58%). Negative remodeling of the PV long axis dimension was observed in 55.2% of veins with a mean reduction of 14.6 ± 9.2% compared to pre-ablation and positive remodeling was observed in 25.3% of PVs with a mean increase in diameter of 14.7 ± 12.6%. Only 1 PV demonstrated a reduction in orifice diameter of > 50%. There were no clinically evident or suspected cases of PV stenosis in this cohort. Conclusions: Negative remodeling of the PV orifice area was noted in the majority of PVs following AF ablation. However, in almost all cases, the extent of negative remodeling was well below commonly used thresholds for the radiographic diagnosis of PV stenosis.

Myocardial viability assessment by PET: (82)Rb defect washout does not predict the results of metabolic-perfusion mismatch.

UNLABELLED: PET is a sensitive technique for the identification of viable myocardial tissue in patients with coronary disease. Metabolic assessment with (18)F-FDG is considered the gold standard for assessment of viability before surgical revascularization. Prior research has suggested that viability may be assessed with washout of (82)Rb between early and late resting images. Our objective was to determine whether assessment of myocardial viability with (82)Rb washout is reliable when compared with PET using (18)F-FDG. METHODS: We performed PET for 194 patients referred for PET (18)F-FDG/(82)Rb to assess viability for clinical indications. We included 151 patients with resting defects >10% of the left ventricle (LV) (n = 159 defects). Patients with smaller resting (82)Rb defects (<10% LV) were excluded for the purpose of this study. PET images acquired with (82)Rb and (18)F-FDG defined viability by the mismatch between metabolism and perfusion ((18)F-FDG >125% of (82)Rb uptake in the (82)Rb defect). Evidence of viability with (82)Rb was assessed by the presence of (i) severity: (82)Rb counts in the defect >50% of (82)Rb in the normal zone of the resting PET images; (ii) washout: decrease of (82)Rb counts in the defect from early to late resting (82)Rb images <17% between the first 90-s image and the final 300-s image; or (iii) combined severity and washout criteria, which required positive criteria for (i) and (ii) to indicate viability. RESULTS: Prevalence of viability by (18)F-FDG/(82)Rb criteria was 50% (n = 79). Severity criteria yielded a sensitivity of 76% and a specificity of 17%, washout criteria yielded a sensitivity of 81% and a specificity of 23%, and both criteria had a sensitivity of 63% and a specificity of 32%. Positive and negative predictive values were poor for all criteria. No correlation existed between (82)Rb washout and (18)F-FDG-(82)Rb mismatch (r(2) = 0.00). Multiple receiver-operating-characteristic plots showed very poor discrimination despite varying criteria for viability by (82)Rb (severity from 50% to 60% of normal zone, washout from 12% to 17%). CONCLUSION: (82)Rb washout from early to late resting images, combined with quantitative severity of the resting (82)Rb defect, did not yield results equivalent to PET (18)F-FDG-(82)Rb mismatch and may not accurately assess myocardial viability.

Comparison of 1.5 and 3.0 T for contrast-enhanced pulmonary magnetic resonance angiography.

OBJECTIVE: In a recent multi-center trial of gadolinium contrast-enhanced magnetic resonance angiography (Gd-MRA) for diagnosis of acute pulmonary embolism (PE), two centers utilized a common MRI platform though at different field strengths (1.5T and 3T) and realized a signal-to-noise gain with the 3T platform. This retrospective analysis investigates this gain in signal-to-noise of pulmonary vascular targets. METHODS: Thirty consecutive pulmonary MRA examinations acquired on a 1.5T system at one institution were compared to 30 consecutive pulmonary MRA examinations acquired on a 3T system at a different institution. Both systems were from the same MRI manufacturer and both used the same Gd-MRA pulse sequence, although there were some protocol adjustments made due to field strength differences. Region-of-interests were manually defined on the main pulmonary artery, 4 pulmonary veins, thoracic aorta, and background lung for objective measurement of signal-to-noise, contrast-to-noise, and bolus timing bias between centers. RESULTS: The 3T pulmonary MRA protocol achieved higher spatial resolution yet maintained significantly higher signal-to-noise ratio (≥13%, p = 0.03) in the main pulmonary vessels relative to 1.5T. There was no evidence of operator bias in bolus timing or patient hemodynamic differences between groups. CONCLUSION: Relative to 1.5T, higher spatial resolution Gd-MRA can be achieved at 3T with a sustained or greater signal-to-noise ratio of enhanced vasculature.

Phase I adjuvant radiation with docetaxel in high-risk head and neck cancer.

BACKGROUND: This phase I study was designed to determine the maximum tolerated dose (MTD) and preliminary efficacy of docetaxel with concurrent radiotherapy (RT), in high-risk squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Eligible patients had resected squamous cell carcinoma of the head and neck, histologically involved lymph nodes, and/or extranodal disease, and/or involved surgical margins and performance status 0 to 1. Treatment included weekly docetaxel with concurrent RT in a dose-finding study; a subsequent small cohort of patients was treated using the MTD of docetaxel. RESULTS: Twenty patients were enrolled. Planned accrual was 25, but the study was closed prematurely because of slow accrual. The MTD was 15 mg/m2. Dose-limiting toxicity was oral stomatitis. Therapy was well tolerated. Five patients experienced locoregional relapse at a median follow-up of 32 months. CONCLUSION: Docetaxel with concurrent RT has acceptable toxicity. This approach warrants further investigation in a phase II trial.

Determination of transmural, endocardial, and epicardial radial strain and strain rate from phase contrast MR velocity data.

PURPOSE: To develop a method for computing radial strain (epsilon) and strain rate (SR) from phase contrast magnetic resonance (PCMR) myocardial tissue velocity data. MATERIALS AND METHODS: PCMR tissue velocity maps were acquired at basal and mid-short-axis slices in the myocardium in 10 healthy volunteers. An algorithm for computing radial strain and SR from PCMR tissue velocity data was developed. PCMR strain values were compared to values computed independently from contours drawn on cine steady-state free procession (SSFP) images. Peak endocardial and epicardial strain and SR values from PCMR data were compared. RESULTS: Excellent agreement was observed between peak strain values computed by PCMR and cine SSFP contours (38.1 +/- 5.4% vs. 38.1 +/- 6.2%; P = not significant [NS]). The presence of an endocardial-epicardial gradient was demonstrated in both strain and SR: peak endocardial values were larger than peak epicardial values in the basal and mid-short-axis slices (P < 0.05). CONCLUSION: This study presents a method for determining radial strain and SR values from PCMR velocity data. This technique illustrates a difference in strain and SR across the myocardium with peak endocardial values being greater than peak epicardial values.

Cross-correlation delay to quantify myocardial dyssynchrony from phase contrast magnetic resonance (PCMR) velocity data.

PURPOSE: To apply cross-correlation delay (XCD) analysis to myocardial phase contrast magnetic resonance (PCMR) tissue velocity data and to compare XCD to three established "time-to-peak" dyssynchrony parameters. MATERIALS AND METHODS: Myocardial tissue velocity was acquired using PCMR in 10 healthy volunteers (negative controls) and 10 heart failure patients who met criteria for cardiac resynchronization therapy (positive controls). All dyssynchrony parameters were computed from PCMR velocity curves. Sensitivity, specificity, and receiver operator curve (ROC) analysis for separating positive and negative controls were computed for each dyssynchrony parameter. RESULTS: XCD had higher sensitivity (90%) and specificity (100%) for discriminating between normal and patient groups than any of the time-to-peak dyssynchrony parameters. ROC analysis showed that XCD was the best parameter for separating the positive and negative control groups. CONCLUSION: XCD is superior to time-to-peak dyssynchrony parameters for discriminating between subjects with and without dyssynchrony and may aid in the selection of patients for cardiac resynchronization therapy.

A new method for the determination of aortic pulse wave velocity using cross-correlation on 2D PCMR velocity data.

PURPOSE: To evaluate the reproducibility of a new multisite axial pulse wave velocity (PWV) measurement technique that makes use of 2D PCMR data and cross-correlation analysis. MATERIALS AND METHODS: PWV was estimated with MRI in 13 healthy volunteers by a transit-time technique (TT), a multisite technique utilizing 1D PCMR data in the descending aorta (FOOT), and a new multisite axial technique that uses 2D PCMR data over the ascending, transverse, and descending sections of the aorta (2D-XC). RESULTS: No significant difference was observed between PWV measurements values measured by the three techniques. However, 2D-XC displayed significantly better intertest reproducibility than either the TT or FOOT methodologies. Average percent difference between scans: TT: 15.8% +/- 13.4%, FOOT: 21.3% +/- 16.9%, 2D-XC: 7.72% +/- 4.73%. P = 0.02 for both 2D-XC/TT comparison and 2D-XC/FOOT comparison. CONCLUSION: 2D-XC is a more reproducible method than either the established TT or FOOT methods to estimate the aortic PWV.

Quantification of left ventricular internal flow from cardiac magnetic resonance images in patients with dyssynchronous heart failure.

PURPOSE: To develop a method for quantifying left ventricular (LV) internal flow as a measure of dyssynchrony using standard cine cardiac magnetic resonance (CMR) images. MATERIALS AND METHODS: CMR images were obtained from 10 healthy controls and 10 patients with dyssynchronous heart failure (class III/IV, LV ejection fraction <35%, pattern seen in an electrocardiogram QRS duration > 150 msec). The LV volume was reconstructed and divided into 16 regions. Internal flow was defined as the sum of the regional volume changes minus the global volume change during each time step in the cardiac cycle. Internal flow fraction (IFF) was defined as the total internal flow as a percentage of stroke volume during systole (IFF(systole)), diastole (IFF(diastole)), or the whole cycle (IFF(whole)). RESULTS: IFF(whole) was significantly increased in the patients (9.9 +/- 5.0% vs. 1.5 +/- 0.5% in the controls, P < 0.001). An IFF(whole) threshold of 4% discriminated between patients and controls with 90% sensitivity and 100% specificity. IFF(diastole) (2.3 +/- 0.8%) was greater than IFF(systole) (0.8 +/- 0.5%) in the normal controls (P < 0.001) while the patients had similar IFF(diastole) (7.8 +/- 4.2%) and IFF(systole) (12.0 +/- 7.8%). CONCLUSION: Left ventricular internal flow fraction can be quantified from standard CMR images. In this preliminary study, Left ventricular internal flow fraction discriminated patients with dyssynchronous heart failure from normal controls with 95% accuracy.

Comparison of myocardial velocities obtained with magnetic resonance phase velocity mapping and tissue Doppler imaging in normal subjects and patients with left ventricular dyssynchrony.

PURPOSE: To compare longitudinal myocardial velocity and time to peak longitudinal velocity obtained with magnetic resonance phase velocity mapping (MR-PVM) and tissue Doppler imaging (TDI), and to assess the reproducibility of each method. MATERIALS AND METHODS: Longitudinal myocardial velocity was measured by TDI and MR-PVM in 10 normal volunteers and 10 patients with dyssynchrony. The reproducibility of MR-PVM and TDI was assessed on repeated measurements in the 10 normal volunteers. RESULTS: MR and TDI measurements of longitudinal myocardial velocity correlated well (r = 0.86) in both normal subjects and patients with dyssynchrony. However, myocardial velocities measured with MR consistently exceeded velocities measured with TDI. MR and TDI agreed strongly in measuring the time to peak velocity (r = 0.97). The reproducibility of TDI and MR-PVM appeared similar in measuring peak velocities (13.1% vs. 11.0%, respectively; P = NS) and time to peak velocity (9.1% vs. 5.7%, respectively; P = NS). CONCLUSION: Excellent correlation and reproducibility were observed between MR-PVM and TDI in measuring longitudinal myocardial velocity and time to peak velocity in both normal subjects and patients with dyssynchrony.

Case report and brief review: IL-2-induced myocarditis.

High dose bolus interleukin 2 (IL-2) used in the treatment of metastatic melanoma and renal cell carcinoma is known to have the potential for serious cardiac toxicity. At our institution 2 of 57 (3.5%) patients developed IL-2 induced myocarditis. The constellation of electrocardiographic changes and elevated troponin I is the hallmark of myocarditis. In this setting of high dose IL-2 therapy it is important to keep myocarditis in the differential in addition to the more frequently sought diagnosis of acute myocardial infarction. Although the gold standard for diagnosis is endomyocardial biopsy, there is considerable false negative rate. It may be reasonable to make the diagnosis on clinical grounds, while providing supportive care. Future investigation is required to better understand the pathophysiology and what factors may influence expression of this toxicity.