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.

Racial disparities in incidence & survival of Kaposi's sarcoma in the United States.

Background & objectives: : In the United States (US), Kaposi's sarcoma (KS) is usually seen in the patients affected by human immunodeficiency virus (HIV). The racial differences in the incidence rates and survival of patients with KS have been reported in the US. We undertook this study to analyse the disparities in the race-specific incidence rate and survival of KS patients of two different races in the US based on SEER (Surveillance, Epidemiology and End Results) database. Methods: Data on KS patients of African-American (AA) and non-Hispanic White (NHW) races who were diagnosed during 1973-2013 were extracted from SEER database to estimate the incidence rates and survival of KS patients. Results: A total of 18,388 NHWs and 3,455 AAs were diagnosed with KS. The age-adjusted incidence rate (AAIR) of KS in patients aged 20-44 yr was 3.8 times higher in AAs than in NHWs. The decline in AAIR of KS among NHWs started during 1989-1994 and preceded decline in the AAIR of AAs. After introduction of highly active antiretroviral therapy (HAART), the incidence continued to decline, but the decrease in the AAIR in AAs [annual percentage change (APC): -6.2; 95% confidence interval (CI): -8.8 to -3.5] was slower than that in NHWs (APC: -10.9; 95% CI: -12.6 to -9.1). The hazard ratio for all-cause mortality in KS patients of the AA race increased from 1.1 (95% CI: 1-1.2) in 1981-1995 to 1.55 (95% CI: 1.4-1.7) in 1996-2013 as compared to those of the NHW race. Interpretation & conclusions: : Several significant racial disparities that emerged after HAART introduction in the incidence and survival of KS patients continued to persist, despite improvement in care of patients with HIV. Further studies need to be done to find out the underlying factors leading to these disparities.

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.

Changing pattern of secondary cancers among patients with malignant thymoma in the USA.

BACKGROUND: The risk of developing secondary cancers (SCs) among patients with malignant thymoma in the US has not been estimated in the more recent time period. Methods: We extracted demographic and treatment data from the SEER database to estimate the standardized incidence ratios (SIRs). Results: Of 1570 patients with thymoma 211 (13.4%) had SCs. The overall risk of developing SCs was higher among patients with thymoma (SIR: 1.54, 95% CI: 1.34-1.76). The SIRs for cancers of lung, esophagus, sigmoid colon, soft tissue and heart, kidney, NHL and leukemia was significantly higher as compared to the general US population. Conclusions: Patients with thymoma are at modestly elevated risk of developing SCs as compared to the general US population. Although the overall risk has not changed after 14 additional years of follow up, the distribution of SCs has significantly broadened, with increased diversity across type and anatomic location of SCs.

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.

A Comparative Study of Primary Adenoid Cystic and Mucoepidermoid Carcinoma of Lung.

BACKGROUND: Pulmonary mucoepidermoid carcinoma (PMEC) and pulmonary adenoid cystic carcinoma (PACC) are the two major types of primary salivary gland-type (PSGT) lung cancers. The demographic profile, clinicopathological features, and predictors of survival as an overall group have not been described for PSGT cancers of lung. METHODS: In this study, we analyzed demographic, clinical, and survival data from 1,032 patients (546 PMEC and 486 PACC) who were diagnosed of PSGT lung cancer in the Surveillance, Epidemiology and End Results database from 1973 to 2014. RESULTS: The PSGT constituted 0.09% of all lung cancers with age-adjusted incidence rate of 0.07 per 100,000 person-years and change of -32% from 1973 to 2014. The incidence of PMEC was slightly higher than PACC but there were no differences in the age and sex distribution. PACCs (55%) were significantly higher at trachea and main bronchus while PMECs were more common at peripheral lungs (85%). Most of the tumors were diagnosed at an early stage and were low grade irrespective of histology. As compared to PMEC, significantly higher number of patients with PACC underwent radical surgery and received adjuvant radiation. The 1- and 5-year cause-specific survival was 76.6 and 62.8%, respectively. On multivariate analysis, the survival was affected by age at diagnosis, tumor stage, histological grade, period of diagnosis, and surgical resection. The histology showed strong interaction with time and hazard ratio of patients with PACC was significantly worse than patients with PMEC only after 5 years. CONCLUSION: The incidence of pulmonary PSGT cancer is 7 cases per 10 million population in the United States and is decreasing. There was no difference between demographic profile of patients with PMEC and PACC but pathological features were diverse. The difference in the survival of patients with the two histological types surfaced only after 5 years when survival of patients with PMEC was better than PACC.

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.

An observational study on risk of secondary cancers in chronic myeloid leukemia patients in the TKI era in the United States.

INTRODUCTION: The treatment with tyrosine kinase inhibitors (TKIs) has drastically improved the outcome of chronic myeloid leukemia (CML) patients. This study was conducted to examine the risk of secondary cancers (SCs) in the CML patients who were diagnosed and treated in the TKI era in the United States. METHODS: The surveillance epidemiology and end results (SEER) database was used to identify CML patients who were diagnosed and received treatment during January 2002-December 2014. Standardized incidence ratios (SIRs) and absolute excess risks (AER) were calculated. RESULTS: Overall, 511 SCs (excluding acute leukemia) developed in 9,200 CML patients followed for 38,433 person-years. The risk of developing SCs in the CML patients was 30% higher than the age, sex and race matched standard population (SIR 1.30, 95% CI: 1.2-1.40; p < 0.001). The SIRs for CLL (SIR 3.4, 95% CI: 2-5.5; p < 0.001), thyroid (SIR 2.2, 95% CI: 1.2-3.5; p < 0.001), small intestine (SIR 3.1, 95% CI: 1.1-7; p = 0.004), gingiva (SIR 3.7, 95% CI: 1.2-8.7; p = 0.002), stomach (SIR 2.1, 95% CI: 1.1-3.5; p = 0.005), lung (SIR 1.4, 95% CI: 1.1-1.7; p = 0.006) and prostate (SIR 1.3, 95% CI: 1.02-1.6; p = 0.026) cancer among CML patients were significantly higher than the general population. The risk of SCs was higher irrespective of age and it was highest in the period 2-12 months after the diagnosis of CML. The risk of SCs in women was similar to that of the general population. CONCLUSION: CML patients diagnosed and treated in the TKI era in the United States are at an increased risk of developing a second malignancy. The increased risk of SCs in the early period after CML diagnosis suggests that the risk of SCs may be increased due to the factors other than TKIs treatment.

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.

Rare Case of Spinal Cord Compression as Initial Presentation of Thymic Carcinoma.

Thymic carcinomas are rare aggressive cancers with limited clinical trial data. Its usual treatment is surgical resection with variable response to chemotherapy and radiation. It usually presents as anterior mediastinal mass with late sequela of metastases to the lymph nodes, pleura and bones. We present of thymic carcinoma with a rare initial presentation of vertebral metastases causing spinal cord compression.

Prostatic Lymphoma Masquerading as Urinary Retention and Hematuria With Review of Literature.

Lymphomas of prostate are very rare tumors. They are not commonly considered in the clinical and histological differential diagnosis of prostatic enlargement. We report a case of a 49-year-old man who presented to emergency department with several weeks of difficulty in urination, for which he was being treated for benign prostate hyperplasia with no improvement. Computerized tomography scan showed lobulated mass originating from the superior aspect of the prostate with right inguinal lymph node involvement and no distant organ metastatic disease. Prostatic biopsy revealed diffuse large B-cell lymphoma. The patient achieved complete remission after six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy regimen. Lymphomas of the prostate should be considered in differential diagnosis of the patient presenting with obstructive lower urinary tract symptoms especially in patients with normal prostatic-specific antigen level and previous history of lymphoma in other sites.

The pattern of secondary cancers in patients with Kaposi sarcoma in the United States.

PURPOSE: In the U.S., Kaposi sarcoma (KS) occurs mostly in HIV-infected patients, who are also at increased risk of developing secondary cancers. The trends in secondary cancer risk are unclear in the HAART era. METHODS: We extracted data from the SEER database on patients diagnosed with KS between 1981 and 2013, stratified into the pre-HAART (1981-1995) and HAART (1996-2013) eras. We compared the risk of secondary cancer in KS patients and the general population, and estimated the absolute risk. RESULTS: We followed 13,535 KS patients for 49,813 person-years, during which 1,041 secondary cancers were diagnosed: 774 in the pre-HAART and 267 in the HAART era. In the pre-HAART era, non-Hodgkin's lymphoma (NHL) and anal carcinomas were the most common secondary cancers. The standard incidence ratio of secondary cancers decreased from 3.44 (pre-HAART era) to 1.94 (HAART era) in patients aged <70 years. The absolute excess risk decreased from 178 to 68 cases per 10,000 person-years. The risk of NHL decreased, while the risk of anal carcinoma did not change significantly. The risk of lung cancer was lower in KS patients than in the general population. The absolute risk of non-AIDS-defining cancers increased fourfold in the HAART era. CONCLUSIONS: The absolute risk of non-AIDS-defining secondary cancers has increased in KS patients in the HAART era. However, the overall relative risk of secondary cancers has decreased, mainly due to a significant decrease in the risk of NHL.

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.