HIV-associated Burkitt lymphoma

Burkitt lymphoma is a rare and aggressive non-Hodgkin lymphoma with three classifications: endemic, sporadic, and immunodeficiency-related. High-intensity chemotherapeutic regimens have considerably improved overall survival for patients with Burkitt lymphoma. In this Review of HIV-associated Burkitt lymphoma, we summarise expert opinion and provide general recommendations for the treatment of Burkitt lymphoma in patients with HIV on the basis of retrospective and prospective studies, taking into consideration immune status, CD4 cell counts, the presence of systemic disease, and the risk of CNS involvement or relapse. We also discuss the role of rituximab and antiretroviral therapy. We highlight the reasons behind the possible different mechanisms of lymphomagenesis in HIV-associated Burkitt lymphoma and endemic Burkitt lymphoma, which indicate that HIV might have either a direct or indirect oncogenic role in Burkitt lymphoma. We discuss the possible mechanisms by which HIV and HIV proteins could directly contribute to lymphomagenesis. Identifying these mechanisms might lead to the development of therapies that have fewer toxic effects than high-intensity chemotherapeutic regimens

Benign ethnic neutropenia

Benign ethnic neutropenia (BEN) is one of the most common causes of chronic neutropenia seen in individuals of African, Middle Eastern and West Indian descent, affecting many individuals worldwide. Despite its prevalence, many physicians are not familiar with this benign condition, resulting in unnecessary evaluation and testing for neutropenia in otherwise healthy individuals. Clinically, patients with BEN are at no increased risk of infection despite their neutropenia. Implications of this condition are highlighted in those patients receiving therapies that have a known side effect of neutropenia, most commonly chemotherapy agents. Studies have suggested that disparities in survival among those patients receiving chemotherapy between patients of European decent and African decent may be attributed to measured neutropenia in these populations, questioning whether BEN could be an influential factor. This review encompasses all aspects of benign ethnic neutropenia, providing information about this condition and helping to guide clinical decision-making as to when an aggressive work up and referral are indicated and when it is appropriate to monitor. Additionally, we review the role of genetic studies in identifying the genes related to BEN, summarize the theories that offer the most accepted mechanisms behind the condition, and address the importance of pursuing larger studies to assess the implication of BEN in oncology patients as well as patients taking neutropenia-causing medications

Drug-Induced Thrombotic Microangiopathy due to Cumulative Toxicity of Ixazomib

Drug-induced thrombotic microangiopathies (DTMAs) are increasingly being recognized as an important category of thrombotic microangiopathies (TMAs). Cancer therapeutic agents including proteasome inhibitors (PIs) are among the most common medications reported to cause DTMA. PIs could cause DTMA either by an immune mechanism or dose-dependent/cumulative toxicity. Eleven cases of DTMA have been reported with bortezomib and carfilzomib. To the best of our knowledge, only one case of DTMA has been reported with ixazomib due to an immune-mediated mechanism. Here, we report the first case of ixazomib-induced DTMA due to cumulative toxicity rather than immune-mediated mechanism. In this article, we discuss the precipitating factors for cumulative toxicity of ixazomib, resulting in DTMA, diagnostic workup, and management of DTMA. We also discuss clinical reasoning based analysis of DTMA versus cancer-associated TMA as well as DTMA versus cyclic thrombocytopenia seen in PI use

Drug-Induced Thrombotic Microangiopathy due to Cumulative Toxicity of Ixazomib

Drug-induced thrombotic microangiopathies (DTMAs) are increasingly being recognized as an important category of thrombotic microangiopathies (TMAs). Cancer therapeutic agents including proteasome inhibitors (PIs) are among the most common medications reported to cause DTMA. PIs could cause DTMA either by an immune mechanism or dose-dependent/cumulative toxicity. Eleven cases of DTMA have been reported with bortezomib and carfilzomib. To the best of our knowledge, only one case of DTMA has been reported with ixazomib due to an immune-mediated mechanism. Here, we report the first case of ixazomib-induced DTMA due to cumulative toxicity rather than immune-mediated mechanism. In this article, we discuss the precipitating factors for cumulative toxicity of ixazomib, resulting in DTMA, diagnostic workup, and management of DTMA. We also discuss clinical reasoning based analysis of DTMA versus cancer-associated TMA as well as DTMA versus cyclic thrombocytopenia seen in PI use

Current and emerging monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies in treatment of lymphoma

The improvement in outcomes seen with the introduction of rituximab, a CD20 monoclonal antibody in combination with chemotherapy or as a single agent in the treatment of indolent non-Hodgkin lymphomas has paved the way for development of various forms of monoclonal antibodies that act in different ways against non-Hodgkin lymphoma tumor cells. These could directly target a single surface antigen resulting in various ways of tumor cells toxicity and killing. Other forms of monoclonal antibodies include antibody-drug conjugates and bispecific antibodies. The role of therapeutic monoclonal antibodies in the treatment of lymphoma will be reviewed, highlighting their mode of action, clinical efficacy, and side effects

Cytokine Based Immunotherapy for Cancer and Lymphoma: Biology, Challenges and Future Perspectives

Cytokines regulate both the innate and adaptive immune responses to cancer. Although antitumor activity has been seen for several cytokines in preclinical models, they have had limited success as single therapeutic agents in clinical trials of cancer immunotherapy. However, the possible combinations of cytokines with other immune therapeutics and the advancement in genetic engineering, synthetic biology and cellular and immune therapy has led to the revival of interest in cytokines as anticancer agents. This article will review several immunostimulatory cytokines with anticancer activity, focusing on the those that have been studied in treatment of lymphoma and highlighting recent advances of potential clinical relevance

Pericardial effusion due to pembrolizumab-induced immunotoxicity: A case report and literature review

The advent of immune checkpoint inhibitors has revolutionized cancer treatment. These novel agents have provided promising treatment options in patients with different types of cancers. One of these agents is pembrolizumab, which works by blocking the binding of T-lymphocytes to programmed cell death ligand 1 receptors on tumor cells, thus enabling immune activation of T-lymphocytes against tumor cells. Pembrolizumab is commonly used in metastatic nonsmall cell lung cancer and melanoma. However, despite the remarkable efficacy this agent has achieved, multiple immune-related adverse events have been reported including hepatitis, colitis, thyroid dysfunction, and pneumonitis. Only 2 other cases of pericardial effusion as a side effect of pembrolizumab have been cited in the literature; however, its incidence may be on the rise. Despite the rarity of this side effect, its complications are potentially life threatening and no clear platform currently exists to help guide healthcare professionals in the management of these adverse events. Herein we present the case of a 66-year-old female who developed pericardial effusion as a side effect of pembrolizumab and review the data currently available to assist in the management of this life-threatening condition

Immune checkpoint inhibitor therapy and myocarditis: a systematic review of reported cases

INTRODUCTION: The advent of immune checkpoint inhibitors in the treatment of certain types of cancers has revolutionized cancer therapy. In general, these novel agents are more tolerable and have better safety profiles than conventional chemotherapy agents. Although a low incidence of myocarditis was noted as a side effect of immune checkpoint inhibitors in clinical trials, it is being increasingly cited in the literature as their use also increases. METHODS: Using a combination of search terms in the PubMed/Medline database and manual searches on Google Scholar and the bibliographies of articles identified, we reviewed all cases reported in the English language citing myocarditis associated with either pembrolizumab, nivolumab, ipilimumab, or any combination of these agents. RESULTS: A total of 42 cases were included in the study. Mean age was 65.5 years; 64% were male, 36% were female. One or two doses preceded the onset of myocarditis in 33% and 29% of cases, respectively. Steroids were used as the first-line therapy in 90% of cases. Complete heart block occurred in 36% of cases. Fourteen (33%) deaths were reported, with 64% and 29% of deaths occurring after one or two doses, respectively. CONCLUSION: Most cases and fatalities of myocarditis occurred shortly after initiation of immune checkpoint inhibitor therapy. Arrhythmias, particularly complete heart block, appear to be related to the occurrence of more severe and fatal cases. The use of serial electrocardiograms or biomarkers of myocardial injury may be crucial in detecting early stages of the disease process. Further research establishing more specific guidelines is necessary in dealing with this potentially fatal side effect

Benign ethnic neutropenia

Benign ethnic neutropenia (BEN) is one of the most common causes of chronic neutropenia seen in individuals of African, Middle Eastern and West Indian descent, affecting many individuals worldwide. Despite its prevalence, many physicians are not familiar with this benign condition, resulting in unnecessary evaluation and testing for neutropenia in otherwise healthy individuals. Clinically, patients with BEN are at no increased risk of infection despite their neutropenia. Implications of this condition are highlighted in those patients receiving therapies that have a known side effect of neutropenia, most commonly chemotherapy agents. Studies have suggested that disparities in survival among those patients receiving chemotherapy between patients of European decent and African decent may be attributed to measured neutropenia in these populations, questioning whether BEN could be an influential factor. This review encompasses all aspects of benign ethnic neutropenia, providing information about this condition and helping to guide clinical decision-making as to when an aggressive work up and referral are indicated and when it is appropriate to monitor. Additionally, we review the role of genetic studies in identifying the genes related to BEN, summarize the theories that offer the most accepted mechanisms behind the condition, and address the importance of pursuing larger studies to assess the implication of BEN in oncology patients as well as patients taking neutropenia-causing medications

Impact of cardiovascular comorbidities on inpatient mortality in patients hospitalized with neutropenic fever

NTRODUCTION: Concomitant cardiovascular comorbidities in patients with cancer are not uncommon. There is limited data on the impact of cardiovascular comorbidities on in-hospital mortality in patients admitted with neutropenic fever. METHODS: This is a retrospective cohort study using the 2016 NIS database of adults (\u3e 18 years old) hospitalized for neutropenic fever as the primary diagnosis. The primary outcome studied is all-cause mortality in patients with neutropenic fever. ICD-10-CM codes were used to identify cardiovascular risk factors including smoking; hyperlipidemia; peripheral vascular diseases; hypertension; history of cerebrovascular disease or transient ischemic attack; and cardiovascular morbidities including atrial fibrillation, coronary artery disease, and congestive heart failure. Multivariate linear regression analysis was used to adjust for cofounders. RESULTS: A total of 28,060 patients were admitted with neutropenic fever in 2016. Average age was 43.9 ± 1.7 years, and 49.3% were females. Among the cases identified, 205 patients died during hospitalization with an overall in-hospital mortality of 0.7%. Atrial fibrillation was independently associated with higher in-hospital mortality (odds ratio [OR] 3.01; CI 1.38 to 6.57; p = 0.005) as was congestive heart failure (OR 3.15; CI 1.08 to 10.14; p = 0.049). CONCLUSION: Atrial fibrillation and congestive heart failure were associated with higher inpatient mortality in patients with neutropenic fever. Identifying the risk factors for increased mortality in patients with neutropenic fever is important for risk stratification and guiding clinicians in taking therapeutic decisions in this set of patients