Myelodysplastic Syndrome in a Patient With Common Variable Immunodeficiency: A Rare Occurrence.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder caused by impaired B-cell function and antibody production. It commonly presents with chronic sinopulmonary and gastrointestinal manifestations. It is also associated with transformation to acute myeloid leukemia. However, the association of CVID with myelodysplastic syndrome (MDS) is rare. This case report aims to present one such rare association in a 26-year-old patient presenting with severe thrombocytopenia. Bone marrow biopsy revealed hypercellular marrow with 80-90% cellularity along with an increase in CD34 blasts. Cytogenetics revealed loss of the Y chromosome. Diagnosis of MDS with excess blasts-2 was confirmed with a Revised International Prognostic Scoring System score of 4, placing the patient in the intermediate-risk category. The patient was started on azacitidine, a hypomethylating agent. A referral to a bone marrow transplant was also done for the consideration of an allogeneic stem cell transplant.

Review of Immune-Related Adverse Events (irAEs) in Non-Small-Cell Lung Cancer (NSCLC)-Their Incidence, Management, Multiorgan irAEs, and Rechallenge.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced malignancies, including non-small cell lung cancer (NSCLC). These agents have improved clinical outcomes and have become quite an attractive alternative alone or combined with other treatments. Although ICIs are tolerated better, they also lead to unique toxicities, termed immune-related adverse events (irAEs). A reconstituted immune system may lead to dysregulation in normal immune self-tolerance and cause inflammatory side effects (irAEs). Although any organ system can be affected, immune-related adverse events most commonly involve the gastrointestinal tract, endocrine glands, skin, and liver. They can occur anytime during the treatment course and rarely even after completion. Owen and colleagues showed that approximately 30% of patients with NSCLC treated with ICIs develop irAEs. Kichenadasse et al. conducted a thorough evaluation of multiorgan irAEs, which is of particular interest because information regarding these types of irAEs is currently sparse. It is important to delineate between infectious etiologies and symptom progression during the management of irAEs. Close consultation with disease-specific subspecialties is encouraged. Corticosteroids are the mainstay of treatment of most irAEs. Early intervention with corticosteroids is crucial in the general management of immune-mediated toxicity. Grade 1-2 irAEs can be closely monitored; hypothyroidism and other endocrine irAEs may be treated with hormone supplementation without the need for corticosteroid therapy. Moderate- to high-dose steroids and other additional immunosuppressants such as tocilizumab and cyclophosphamide might be required in severe, grade 3-4 cases. Recently, increasing research on irAEs after immunotherapy rechallenge has garnered much attention. Dolladille and colleagues assessed the safety in patients with cancer who resumed therapy with the same ICIs and found that rechallenge was associated with about 25-30% of the same irAEs experienced previously (4). However, such data should be carefully considered. Further pooled analyses may be required before we conclude about ICIs' safety in rechallenge.

Blood and Marrow Transplant Clinical Trials Network Study 1102 heralds a new era in hematopoietic cell transplantation in high-risk myelodysplastic syndromes: Challenges and opportunities in implementation.

LAY SUMMARY: People who have advanced myelodysplastic syndromes (MDS) may live longer if they get a bone marrow transplant (BMT) instead of other therapies. However, only 15% of people with MDS actually get BMT. Experts say community physicians and transplant physicians should team up with insurance companies and patient advocacy groups to 1) spread this news about lifesaving advances in BMT, 2) ensure that everyone can afford health care, 3) provide emotional support for patients and families, 4) help patients and families get transportation and housing if they need to travel for transplant, and 5) improve care for people of under-represented racial and ethnic backgrounds.

Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence.

Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage has led to the modern era of immunotherapy in cancer treatment. Agents that release these immune brakes have shown activity to recover dysfunctional T cells and regress various cancer. Both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death-1 (PD-1) play their role as physiologic brakes on unrestrained cytotoxic T effector function. CTLA-4 (CD 152) is a B7/CD28 family; it mediates immunosuppression by indirectly diminishing signaling through the co-stimulatory receptor CD28. Ipilimumab is the first and only FDA-approved CTLA-4 inhibitor; PD-1 is an inhibitory transmembrane protein expressed on T cells, B cells, Natural Killer cells (NKs), and Myeloid-Derived Suppressor Cells (MDSCs). Programmed Death-Ligand 1 (PD-L1) is expressed on the surface of multiple tissue types, including many tumor cells and hematopoietic cells. PD-L2 is more restricted to hematopoietic cells. Blockade of the PD-1 /PDL-1 pathway can enhance anti-tumor T cell reactivity and promotes immune control over the cancerous cells. Since the FDA approval of ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) in 2011, six more immune checkpoint inhibitors (ICIs) have been approved for cancer therapy. PD-1 inhibitors nivolumab, pembrolizumab, cemiplimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab are in the current list of the approved agents in addition to ipilimumab. In this review paper, we discuss the role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN), which is broadly utilized by medical oncologists and hematologists in their daily practice.

Primary renal lymphoma: A population-based analysis using the SEER program (1973-2015).

OBJECTIVE: Primary renal lymphoma (PRL) is defined as a non-Hodgkin lymphoma (NHL) restricted to kidneys without extensive nodal disease. The literature on epidemiology and outcome in PRL is limited to case reports and small case series. METHODS: We utilized Surveillance, Epidemiology, and End Result database (1984-2015) to study the demographic, clinical, and pathological characteristics of PRL. We conducted analysis to assess factors associated with overall survival (OS) and cause-specific survival (CSS). RESULTS: A total of 599 (0.17% of all NHL) patients were eligible for the study. The age-adjusted incidence was 0.035/100,000 population and is increasing. The median age was 72 years, and most of the patients were Caucasians and were males. Most of the patients had unilateral tumors, and diffuse large B-cell lymphoma (DLBCL) was the most common histologic type. The median OS was 112 months, while median CSS was not reached. Age ≥ 60 years was the strongest independent risk factor for worse OS and CSS, while non-DLBCL histology was associated with better OS and CSS. DISCUSSION: Primary renal lymphoma is a rare lymphoma with increasing incidence in more recent years. In this study, we describe demographic, clinical, and pathological characteristics of PRL and factors affecting survival among these patients.

Emerging Therapies in the Management of Advanced-Stage Gastric Cancer.

Globally, gastric malignancy contributes to significant cancer-related morbidity and mortality. Despite a recent approval of two targeted agents, trastuzumab and ramucirumab, the treatment options for advanced-stage gastric cancer are limited. Consequently, the overall clinical outcomes for patients with advanced-stage gastric cancer remain poor. Numerous agents that are active against novel targets have been evaluated in the course of randomized trials; however, most have produced disappointing results because of the molecular heterogeneity of gastric cancer. The Cancer Genome Atlas (TCGA) project proposed a new classification system for gastric cancer that includes four different tumor subtypes based on molecular characteristics. This change led to the identification of several distinct and potentially targetable pathways. However, most agents targeting these pathways do not elicit any meaningful clinical benefit when employed for the treatment of advanced-stage gastric cancer. Most advanced-stage gastric cancer trials currently focus on agents that modulate tumor microenvironments and cancer cell stemness. In this review, we summarize data regarding novel compounds that have shown efficacy in early phase studies and show promise as effective therapeutic agents, with special emphasis on those for which phase III trials are either planned or underway.

A comparison between two types of indwelling pleural catheters for management of malignant pleural effusions.

BACKGROUND: Malignant pleural effusion (MPE) is a common cause of quality of life deterioration in patients with advanced cancer. Management options include chemical pleurodesis with a sclerosing agent such as doxycycline or talc powder, surgery, and also the placement of tunneled indwelling pleural catheters (IPCs). Two different IPC types are mostly used in the USA. METHODS: We conducted a single-center retrospective study with the objective to compare the efficacy and safety profiles of two IPC systems. Patients with a diagnosis of malignancy, who received IPCs by the interventional radiology department of our hospital from January 2013 to March 2015, were identified in the local database and a chart review was performed to record characteristics and outcomes. Patients without a diagnosis of malignancy or with pleural effusions of cardiac origin were excluded from the study. RESULTS: We identified 27 patients with a median age of 59.0 years. Eighty patients received Aspira catheter while nine patients received PleurX catheter, and seven patients achieved spontaneous pleurodesis. The median length of stay (LOS) was 9 days for the Aspira group (AG), as compared to 13 days for the PleurX group (PG) (overall median LOS was 10 days; range, 2-62 days). The rate of catheter-related complications (pain, obstruction, loculations, infection, hemorrhage) was 39% (seven patients) for the AG and 33% (three patients) for the PG (overall ten patients, 37%). CONCLUSIONS: In our study, outcomes and safety were similar for patients receiving either type of IPC, Aspira or PleurX.

Trends in the Risks of Secondary Cancers in Patients With Hodgkin Lymphoma.

INTRODUCTION: The present study analyzed the trends in secondary cancer (SC) risks among Hodgkin lymphoma (HL) patients in the United States. MATERIALS AND METHODS: Patients with HL diagnosed from 1973 to 2014 were identified from the Surveillance, Epidemiology, and End Results database. We compared the risk of SCs in HL patients relative to the risk in the US general population across 3 periods: 1973 to 1986, 1987 to 2000, and 2001 to 2014 to study the effect of treatment practices on the development of SCs. RESULTS: In a follow-up study of 23,864 HL survivors for 284,730 person-years, 3260 SCs were diagnosed with a standardized incidence ratio (SIR) of 1.97 (95% confidence interval [CI], 1.9-2.04). A statistically significant decrease was found in the overall SIRs of SCs diagnosed in HL patients from 1987 to 2000 (SIR, 1.82; 95% CI, 1.72-1.93) and from 2001 to 2014 (SIR, 1.66; 95% CI, 1.51-1.82) relative to patients with SCs diagnosed from 1973 to 1986 (SIR, 2.24; 95% CI, 2.13-2.35). The decline in the overall SIR mostly resulted from declines in digestive tract and breast cancers. The SIRs of most other solid tumors and hematologic malignancies did not decrease. After adjusting for age, gender, and race, patients with a diagnosis from 1973 to 1986 had a 12% greater risk of developing SCs (hazard ratio, 1.12; 95% CI, 1.03-1.23; P = .01) compared with the patients with a diagnosis from 1987 to 2000. CONCLUSION: Although the overall risk of SCs in patients with HL declined after modifications in HL treatment, the risk did not change significantly at most individual sites. Thus, close follow-up with active surveillance for SCs is crucial for long-term survivors of HL.

Bortezomib-Induced Pulmonary Toxicity: A Case Report and Review of Literature.

Bortezomib, a proteasome inhibitor, is an established therapy against multiple myeloma. Bortezomib-induced lung injury, although not appreciated during the introductory time of the medication, has now been highlighted in multiple case reports. The objective of this study is to report a case of bortezomib-induced lung injury, review current literature, and perform exploratory analysis.

Corrigendum: Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy.

[This corrects the article on p. 49 in vol. 8, PMID: 28228726.].

Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy.

The indications of immune checkpoint inhibitors (ICIs) are set to rise further with the approval of newer agent like atezolimumab for use in patients with advanced stage urothelial carcinoma. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs). The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems. There are new safety data accumulating on ICIs in patients with previously diagnosed autoimmune conditions. It is challenging for clinicians to continuously update their working knowledge to diagnose and manage these events successfully. If diagnosed timely, the majority of events are completely reversible, and temporary immunosuppression with glucocorticoids, infliximab or other agents is warranted only in the most severe grade illnesses. The same principles of management will possibly apply as newer anti- cytotoxic T lymphocytes-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1/PD-L1) antibodies are introduced. The current focus of research is for prophylaxis and for biomarkers to predict the onset of these toxicities. In this review we summarize the irAEs of ICIs and emphasize their growing spectrum and their management algorithms, to update oncology practitioners.

Recurrent Arterial Thrombosis as a Presenting Feature of a Variant M3-Acute Promyelocytic Leukemia.

Acute limb ischemia (ALI) is a common vascular emergency. Hematologic malignancies are commonly associated with derangement of normal hemostasis and thrombo-hemorrhagic symptoms during the course of the disease are common. However, ALI as an initial presenting feature of acute leukemia is rare. Due to the rarity of this presentation, there is a scarcity of prospective randomized data to optimally guide the management of these patients. Current knowledge is mainly based on isolated cases. We report our experience managing a patient who presented with ALI and was found to have occult leukemia. A review of all cases with ALI as a presenting feature of acute leukemia is also presented.

Primary Hepatic Osteosarcoma: A Rare Cause of Primary Liver Tumor.

INTRODUCTION: Extraosseous osteosarcomas are rare, accounting for approximately 4% of all osteosarcomas. A literature review yields very few cases of osteosarcoma primarily arising from the hepatic parenchyma. CASE REPORT: This report describes a case of a man in his 50s with a history of hepatitis C and cirrhosis who presented with 5 days of progressive right upper quadrant pain. Magnetic resonance imaging of the abdomen and pelvis demonstrated a 4.4 cm × 4.8 cm × 4.8 cm right hepatic lobe mass with a large area of necrosis and peripheral enhancement. The subsequent liver biopsy showed few cores of tumor composed of fibroblastic malignant cells producing lace-like osteoid matrix. Osteosarcomatous foci in other parts of the body were excluded by performing extensive physical examination, radiologic imaging, and biopsy. Hence, a primary osteosarcoma was diagnosed. The patient underwent portal vein embolization in preparation for a surgical resection of the right liver lobe. He was admitted six weeks after the embolization for dyspnea and abdominal distension and expired due to abdominal hematoma and pulmonary embolism. CONCLUSION: Based on the rarity, lack of consensus in treatment, and dismal prognosis, extraosseous osteosarcoma should be considered a separate entity from osseous osteosarcoma. More data and research are needed in this rare and understudied malignancy.

Vemurafenib in leptomeningeal carcinomatosis from melanoma: a case report of near-complete response and prolonged survival.

Targeted therapies such as the BRAF inhibitors vemurafenib and dabrafenib are highly effective in the treatment of systemic metastatic melanoma and have been shown to be effective in controlling solid brain metastases; however, limited data exist on their activity in leptomeningeal spread. Here, we present a case of a 60-year-old woman who developed leptomeningeal carcinomatosis from melanoma after resection and stereotactic radiotherapy of melanoma brain metastases, with poor performance status, who received vemurafenib as first-line treatment, resulting in significant clinical and imaging response as well as prolonged survival.

Disseminated tuberculosis secondary to adalimumab.

A 62-year-old woman with rheumatoid arthritis presented with fever (T-103.9°F). Vital signs and physical examination were normal. She was taking adalimumab, methotrexate, and prednisone for the past 9 months. Blood and urine cultures, human immunodeficiency virus, rapid plasma reagin, purified protein derivative, and cerebrospinal fluid test findings were negative. Computed tomography showed scattered 0.2-cm nodules in the lungs and innumerable subcentimeter lesions in the liver and spleen. Broad-spectrum antibiotics were started empirically. Liver biopsy findings revealed necrotizing granulomas and were negative for acid fast bacilli and fungi on staining. As the patient was persistently febrile despite antibiotics, the antibiotics were discontinued, and an antituberculous regimen including INH, ethambutol, and pyrazinamide was initiated empirically on day 40 of hospitalization. Fourteen days after liver biopsy, acid-fast bacilli grew in the tissue culture. Disseminated tuberculosis (TB) was diagnosed. Fever subsided after 1 week of anti-TB treatment. Antitumor necrosis factor alpha therapy in rheumatoid arthritis increases the risk of TB 5-fold. This is mostly as a result of reactivation of latent TB and commonly presents as disseminated TB. It usually occurs in the early stage of treatment. In our patient, the screening test results for TB before initiation of Adalimumab could have been falsely negative due to immunosuppression secondary to steroids. Our case emphasizes that current screening tests can miss latent TB especially in immunosuppressed patients. As it is difficult to diagnose TB with polymerase chain reaction and culture, histopathology should be sought early. Patients on antitumor necrosis factor alpha therapy presenting with fever of unknown origin should be considered for empirical anti-TB treatment regardless of microbiological and tissue diagnosis.

Protothecal olecranon bursitis: an unusual algal infection.

Prototheca is an achlorophyllic alga which rarely causes infections in humans and protothecal olecranon bursitis is remarkably rare. We report a case of a 76-year-old immunocompetent man presenting with pain and swelling of the right elbow secondary to protothecal infection. Initial cultures of the olecranon bursal aspirate revealed no growth; however, repeat aspiration after 2 months grew prototheca species on culture. Prototheca wickerhamii and Prototheca zopfii are the only 2 protothecal species known to cause human infections. Protothecal infection can manifest as skin infections, extremity infections, bursitis and very rarely as systemic infections. Treatment of protothecal infections remains controversial. Amphoterecin B, ketoconazole and fluconazole have been reported to yield a successful outcome. More recently, itraconazole has been found to be curative. Surgical excision of the bursa remains the definitive treatment. Our patient was treated with itraconazole with a favorable response.

Repetitive monomorphic ventricular tachycardia as a manifestation of suboptimally treated thyrotoxicosis.

Monomorphic ventricular tachycardia (VT) is a unique manifestation of hyperthyroidism. We present the case of a 41-year-old male with a history of hyperthyroidism presenting with palpitations secondary to non-sustained episodes of monomorphic VT. Cardiac arrhythmias due to thyrotoxicosis are perpetually supraventricular in origin. Monomorphic VT in the setting of thyrotoxicosis in the absence of structural heart disease is exceedingly rare. After starting propranolol and increasing the dose of methimazole, the patient had no further episodes of VT. It is important to recognize repetitive monomorphic VT as an understated but important manifestation of thyrotoxicosis. Propranolol is associated with an excellent response in these patients and anti-thyroid medications such as methimazole effectively reverse thyrotoxicity.

Brugada syndrome unmasked by lithium.

A 38-year-old man was brought by emergency medical service after resuscitation following cardiac arrest. The patient was found pulseless with a wide complex tachycardia. The patient had bipolar disorder and was on lithium, lamotrigine, and ziprasidone. His electrolytes and lithium levels were normal. An electrocardiogram (EKG) was performed the next day and showed type 1 Brugada pattern. Lithium was held. Electrophysiologists made a diagnosis of drug-unmasked Brugada syndrome. Lithium can unmask Brugada syndrome through its ability to block sodium channels, even at subtherapeutic concentrations. Physicians need to be aware of this potentially fatal drug effect and should monitor EKGs of patients on lithium.

Tako-tsubo cardiomyopathy following electroconvulsive therapy.

A 70-year-old woman with extensive psychiatric history, including depression and bipolar disorder, and past medical history of mitral valve prolapse repair (3 years ago) was brought in from the psychiatry ward to the emergency department for evaluation of ECG changes following electroconvulsive therapy (ECT). ECG done after the procedure showed ST elevations in V2-V3 and new T-wave inversions in the precordial leads. Troponin level was 0.23 ng/ml. An echocardiogram revealed apical akinesis with segmental wall motion abnormalities and a decreased ejection fraction of 30-35%. Cardiac catheterization revealed clean coronaries. A repeat echocardiogram 6 weeks after the event showed a normal ejection fraction. A diagnosis of tako-tsubo cardiomyopathy was made. ECT causes a significant increase in bigeminy, trigeminy, and supraventricular tachycardia. ECT is associated with a low mortality rate; in the range of 0.01-0.1% and 75% of these are attributable to cardiovascular causes. To our knowledge, this is the first reported case of tako-tsubo syndrome immediately following electroconvulsive therapy.