case report

Heart of the Matter: Reversal of Systolic Heart Failure and Long Term Remission in Primary Cardiac Lymphoma with Multi-Agent Chemotherapy with Continuous Intravenous Administration of Doxorubicin

Alyssa MacKay1, Jai Singh2, Jared Block3, Shebli Atrash4, Nilanjan Ghosh4, Bei Hu4*

1Department of Internal Medicine, Atrium Health, Charlotte, NC, USA

2Department of Cardiology, Sanger/Atrium Health, Charlotte, NC, USA

3Carolinas Pathology Group, Atrium Health, Charlotte, NC, USA

4Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Atrium Health, Charlotte, NC, USA

*Corresponding author: Bei Hu, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute-Atrium Health/Wake Forest, Charlotte, NC, USA

Received Date: 13 April 2023

Accepted Date: 17 April 2023

Published Date: 19 April 2023

Citation: MacKay A, Singh J, Block J, Atrash S, Ghosh N, et al. (2023) Heart of the Matter: Reversal of Systolic Heart Failure and Long Term Remission in Primary Cardiac Lymphoma with Multi-Agent Chemotherapy with Continuous Intravenous Administration of Doxorubicin. Ann Case Report 8: 1266. DOI: https://doi.org/10.29011/2574-7754.101266

Abstract

Primary cardiac lymphoma is rare with diffuse large B cell lymphoma being the most common histology. The main treatment modality is anthracycline based chemotherapy, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus rituximab (anti-CD20 monoclonal antibody). However, regimens containing doxorubicin are often used with caution as heart failure is a common presenting feature of primary cardiac lymphoma. We present a case of a patient with diffuse large B cell lymphoma of the myocardium presenting with cardiogenic shock who achieved long-term remission and reversal of biventricular heart failure after receiving RCHOP with continuous infusion doxorubicin.

Keywords: Diffuse Large B-cell Lymphoma (DLBCL); Cardiac Lymphoma; Systolic Heart Failure

Introduction

Primary Cardiac Lymphomas (PCL) are rare and account for 1% of primary cardiac tumors, with Diffuse Large B-Cell Lymphoma (DLBCL) being the most common histology [1]. While there is no standard of care, patients are often treated with multiagent chemotherapy which can be challenging as heart failure can be the presenting symptom in nearly half of the cases [1]. With the DLBCL subtype, there have been case reports of long-term survival with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and REPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) chemotherapy, sometimes used in combination with radiation [2-4]. In the largest case series of 197 patients with cardiac lymphoma, the long-term overall survival was 40% [1].

Continuous intravenous administration of doxorubicin has been used as an alternative to bolus administration to reduce incidence of cardiotoxicity by 75% [5, 6]. In the NCCN guidelines, dose adjusted REPOCH is an acceptable alternative to RCHOP for those with poor cardiac function. Herein, we describe a case of primary cardiac lymphoma, DLBCL subtype who presented with cardiogenic shock but achieved complete remission with multiagent chemotherapy containing rituximab and infusional doxorubicin.

Case Report

A 67-year-old HIV-negative, physically active female with hypertension presented with a one week history of fatigue, night sweats, midsternal chest pressure, dyspnea on exertion, nausea and vomiting. Initial ECG showed sinus rhythm with diffuse ST-segment elevation with an elevated troponin of 0.38 ng/dL. Transthoracic Echocardiogram (TTE) revealed a Left Ventricular Ejection Fraction (LVEF) of 30-35%, grade 2 diastolic dysfunction, apical hypokinesis with severe apical hypertrophy and a small pericardial effusion. She underwent left heart catheterization which showed non-obstructive coronary artery disease with concern for an infiltrative cardiomyopathy as multiple coronary arteries appeared stuck in her myocardium. Cardiac MRI revealed a reduction in left and right ventricular volumes and function as well as concentric endocardial thickening and subendocardial hyperenhancement of the apical half of the left and right ventricles suggestive of endomyocardial fibrosis. Subsequent right heart catheterization with cardiac biopsy showed a severely depressed cardiac output of 1.66 with cardiac index of 0.96. Due to low cardiac output from biventricular failure, hypotension, in addition to hepatic and renal failure, she was placed on dopamine and milrinone drips and transferred for higher level of care. Repeat TTE showed a LVEF of 15% with left ventricular contraction preserved in the basal segments and severely reduced contraction in the mid and apical segments. Her hospital course was further complicated by multiple arrhythmias including atrial fibrillation and flutter requiring amiodarone, bilateral pleural effusions negative for lymphoma requiring thoracentesis, and re-expansion pulmonary edema.

Myocardial biopsy ultimately revealed the diagnosis of non-germinal center subtype DLBCL positive for CD10, CD20, CD79a, MUM-1, BCL 6, and BCL-2. Ki-67 with proliferation rate 90% and negative for CD68 and CD43, (Figure 1). PET/CT showed irregular FDG activity along the cardiac apex with no other metabolically active disease consistent with Stage IE disease. She was then initiated on RCVP (Rituximab, Cyclophosphamide, Vincristine, And Prednisone) with rituximab given at 50cc/hr and cyclophosphamide given in a hyperfractionated pattern to avoid ventricular perforation. Notably, doxorubicin was omitted due to a LVEF of 15%. After one cycle, she was weaned off of vasopressor support; repeat cardiac MRI showed improvement in LVEF to 42% (Figure 2). After cycle two, cardiac MRI showed improvement in LVEF to 56%. Given improvement in her cardiac function she continued treatment with curative intent. She was subsequently given RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for cycles 3-5 of treatment. Doxorubicin was given at half the recommended dose in a 25mg/m2 infusion over 48 hours due to her tenuous cardiac status and previous administration of amiodarone. She ultimately completed five cycles of chemotherapy with a total dose of 75mg/m2 of doxorubicin which led to complete remission. PET/CT showed no metabolically active disease and resolution of previous abnormal uptake at the cardiac apex. She remained in remission at 2 years; however, she ultimately passed away from septic shock, unrelated to lymphoma or cancer associated treatment.

 

Figure 1: Final pathology consistent with non-germinal center subtype DLBCL. Shown here are the immunohistochemistry features of primary cardiac lymphoma from myocardial biopsy. A. H&E stain B. Ki-67 proliferation activity.