Co-existence of Antiphospholipid syndrome and Heparin-induced Thrombocytopenia in a patient with Recurrent Venous Thromboembolism.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction in which heparin forms complexes with platelet factor 4 forming neoantigens that are recognized by autoantibodies. Antiphospholipid syndrome (APS) is similar to HIT in that it is mediated by autoantibodies that are also pro-thrombotic. We present a case of rare co-existence of antiphospholipid antibody syndrome and heparin-induced thrombocytopenia. Introduction Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction in which heparin forms complexes with platelet factor 4 forming neoantigens that are recognized by autoantibodies (antiHPF4/HAPA). The Fc portions of the anti-HPF4 bind Fc receptors on platelets causing platelets activation, aggregation, release of α and dense granules and formation of procoagulants [1]. The hallmark of this is thrombocytopenia and thrombosis. HIT occurs in about 2% of all patients who receive heparin of whom about 35% develop thrombosis [2]. Antiphospholipid syndrome (APS) is similar to HIT in that it is mediated by autoantibodies that are also pro-thrombotic. Autoantibodies are generated to phospholipids or to phospholipid-binding proteins which are recognized risk-factors for thrombosis and pregnancy morbidity. Diagnosis of APS requires the elevation of at least one of the phospholipid autoantibodies and a clinical manifestation (Table 1). In this report we present a patient with recurrent venous thromboembolism despite been on full anticoagulation who was found to have concurrent HIT and APS

An Extremely Indolent T-cell Leukemia: An 18-year Follow-Up.

T-cell prolymphocytic leukemia (T-PLL) is a rare malignancy that comprises about 2% of all mature lymphoid neoplasms. Patients usually present with prominent peripheral blood lymphocytosis, splenomegaly, hepatomegaly, lymphadenopathy, B symptoms, and occasionally with skin lesions.¹ The disease follows an aggressive clinical course with rapid progression and typically has a median survival of less than 1 year. In some cases, the disease is indolent for a period of time before becoming aggressive.² In 2002, 7 years after initial diagnosis in 1995, the case discussed herein was reported as a rare, indolent form of T-PLL.³ We now present 11 additional years of follow-up of this case, during which time the patient remained asymptomatic with respect to his lymphoid neoplasm

A rare case of acute lymphoblastic leukemia in a patient with light chain (AL) amyloidosis treated with lenalidomide.

Lenalidomide belongs to a novel class of drugs called Immunomodulators which are now being used for the treatment of plasma cell dyscrasias with variable degrees of efficacy and toxicity. Though Second Primary Malignancies (SPM) have been a concern with its use, the benefits of the treatment outweigh the risks. The leukemogenic risk seems to be potentiated especially when combined with alkylating agents and the SPMs documented are predominantly myeloblastic. To date there are no reported cases of new lymphocytic leukemias in AL amyloidosis, regardless of whether undergone treatment or not. We present a case of AL amylodosis who was treated with lenalidomide and subsequently developed acute lymphoblastic leukemia

Clinical Characteristics and Treatment-Related Biomarkers Associated with Response to High-Dose Interleukin-2 in Metastatic Melanoma and Renal Cell Carcinoma: Retrospective Analysis of an Academic Community Hospital\u27s Experience.

Background Immunotherapy in the treatment of metastatic melanoma and renal cell carcinoma can produce durable therapeutic responses, which may improve survival. We aimed to identify clinical characteristics and biomarkers associated with response to high-dose interleukin-2 therapy (IL-2) in patients with metastatic melanoma and renal cell carcinoma treated at an academic community hospital. Patients/Methods We retrospectively analyzed clinical variables and biomarkers of 50 consecutive metastatic melanoma or renal cell carcinoma patients treated at our institution with IL-2 during 2004 – 2012. We evaluated clinical characteristics: metastatic sites of disease, prior therapies, number of IL-2 doses per cycle, response duration, autoimmune phenomena, and peak fever, as well as laboratory biomarkers: baseline LDH, platelet nadir, and baseline and highest absolute lymphocyte count (ALC). Survival outcomes were calculated using Kaplan-Meier curves. Results Variables differing between responders (clinical benefit group) and non-responders (no clinical benefit group) in metastatic melanoma included platelet nadir during treatment (p = 0.015), autoimmune phenomena (p = 0.049), and in renal cell carcinoma, platelet nadir (p = 0.026). There were no significant differences between number of doses of IL-2 received per cycle and response in either cancer subtype. Clinical benefit occurred in 25% of patients (9/36) when IL-2 was given as first-line therapy. Median overall survival for the clinical benefit group from the initiation of IL-2 to death or last follow-up was 61 months versus 17 months for the no clinical benefit group (p \u3c 0.001) for metastatic melanoma. In renal cell carcinoma overall survival for clinical benefit patients was 48 months versus 17 months. No treatment-related deaths occurred. Conclusions High-dose IL-2 can be safely administered by an experienced team in a non–intensive care oncology unit. The clinical benefit group developed autoimmune phenomena (melanoma patients), lower platelet nadir, and on average, received the same number of IL-2 doses as the no clinical benefit group, suggesting a response relationship to the patient’s baseline immune status. Further investigation of immune predictors of response may be useful to select appropriate patients for this therapy. Keywords: Interleukin-2, Metastatic melanoma, Metastatic renal cell carcinoma, IL-2, Biomarkers, Safety, Respons

Effect of the Tyrosine Kinase Inhibitors (Sunitinib, Sorafenib, Dasatinib, and Imatinib) on Blood Glucose Levels in Diabetic and Non-diabetic Patients in General Clinical Practice (Poster)

Tyrosine kinase is a key enzyme activity utilized in many intracellular messaging pathways. Understanding the role of particular tyrosine kinases in malignancies has allowed for the design of tyrosine kinase inhibitors (TKIs), which can target these enzymes and interfere with downstream signaling. TKIs have proven to be successful in the treatment of chronic myeloid leukemia, renal cell carcinoma and gastrointestinal stromal tumor, and other malignancies. Scattered reports have suggested that these agents appear to affect blood glucose (BG). We retrospectively studied the BG concentrations in diabetic (17) and nondiabetic (61) patients treated with dasatinib (8), imatinib (39), sorafenib (23), and sunitinib (30) in our clinical practice. Mean declines of BG were dasatinib (53 mg/dL), imatinib (9 mg/dL), sorafenib (12 mg/dL), and sunitinib (14 mg/dL). All these declines in BG were statistically significant. Of note, 47% (8/17) of the patients with diabetes were able to discontinue their medications, including insulin in some patients. Only one diabetic patient developed symptomatic hypoglycemia while on sunitinib. The mechanism for the hypoglycemic effect of these drugs is unclear, but of the four agents tested, c-kit and PDGFRβ are the common target kinases. Clinicians should keep the potential hypoglycemic effects of these agents in mind; modification of hypoglycemic agents may be required in diabetic patients. These results also suggest that inhibition of a tyrosine kinase, be it c-kit, PDGFRβ or some other undefined target, may improve diabetes mellitus BG control and it deserves further study as a potential novel therapeutic option

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types