Cost reduction associated with heparin-induced thrombocytopenia panel ordering for enoxaparin versus heparin for prophylactic and therapeutic use: A retrospective analysis in a community hospital setting.

BACKGROUND: Most hospitals still use unfractionated heparin (UFH) as the primary agent for venous thromboembolism (VTE) prophylaxis in the hospital setting due to ease of use and insignificant cost. However, the risk of heparin-induced thrombocytopenia (HIT) has led some groups to favor other options for therapeutic and prophylactic anticoagulation. This is particularly relevant in light of recent data demonstrating a lower rate of HIT in patients receiving enoxaparin compared with UFH. This study examines the cost-effectiveness of enoxaparin, compared to UFH for prophylactic and therapeutic usage in hospitals. METHODS: We conducted a retrospective chart review of patients who underwent HIT panel testing at the Inspira Health Network, Vineland campus (an approximately 262-bedded community hospital located in southern New Jersey that services a population of approximately 61,050) from the period of April 1, 2015 through December 31, 2016. The starting date represents the time from which enoxaparin became the primary alternative anticoagulant available at this hospital. Records of the total usage and cost of UFH and enoxaparin for the specified time period were collected from the hospital pharmacy database for evaluation, as were records of HIT panels. The information was analyzed to determine the frequency of HIT panel testing orders for patients receiving UFH versus those receiving enoxaparin. Annual cost-savings for the hospital were extrapolated using the comparative incidence of HIT panels and associated costs, including increased length of stay, hematology/oncology consultation, use of an alternative anticoagulant, critical bleeding requiring transfusion, and complications of HIT-associated thrombosis. These variables were multiplied by the incidence rate for each specified drug and usage to determine the daily cost for each drug. RESULTS: The use of enoxaparin did not result in a significant decrease in the ordering of HIT panels in the hospital, with a relative rate ratio of 0.948 (95% confidence interval: 0.336, 2.21). When the data were stratified to examine prophylactic and therapeutic anticoagulation, there was a marked difference in the frequency of HIT testing. The rate ratio of HIT panel orders for patients receiving therapeutic enoxaparin rather than intravenous (IV) UFH was 0.118 (0.006, 0.625). These numbers were used to extrapolate the total daily cost of enoxaparin compared with IV UFH; therapeutic enoxaparin cost $30.66, while IV UFH cost $162.30. IV UFH use was associated with a higher incidence rate of HIT panel orders, and consequently a higher daily cost due to the likelihood of increased length of stay, use of alternative anticoagulation, bleeding requiring transfusion, and request for expert consultation. CONCLUSION: In this study, the use of enoxaparin was associated with a significant cost-saving over IV UFH when used for therapeutic anticoagulation, but this cost saving was not observed for prophylactic anticoagulation.

Clinical updates in adult acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a clonal disease characterized by B or T lineage. Here we cover the clinical manifestations, pathophysiology and therapy for ALL. Additionally, we will discuss the evidence for minimal residual disease assessment, novel molecular targets and newly developed targeted therapies. The separation of ALL into Philadelphia chromosome positive and recently into Philadelphia-like disease represents the most exciting developments in this disease. Finally, the advent of new immunotherapeutic approaches led us to predict that in few years, ALL therapy might be based heavily on non-chemotherapeutic approaches.

Swallowing a bitter pill-oral arsenic trioxide for acute promyelocytic leukemia.

Parenteral arsenic trioxide (ATO) has been firmly established as a standard therapy for acute promyelocytic leukemia (APL). Despite widespread use of oral arsenicals in medicine historically, they had disappeared from modern pharmacopeia until oral ATO was redeveloped in Hong Kong in 2000. Since then, over 200 patients with leukemia (predominantly APL) have been treated with oral ATO in Hong Kong and China. Oral arsenic trioxide and other formulations of arsenic appear to have a clinical efficacy comparable to that of IV formulations. These drugs given orally also appear to have a slightly better safety profile, lower operational costs and improved convenience for patients. The clinical experience with oral ATO has previously been reported piecemeal as case series, pilot studies or subgroup analyses rather than in a comprehensive cohort. In this report we attempt to synthesize the published English language literature on oral arsenicals and present the argument for further development of these compounds. Systematic study of this drug with well-designed randomized multi-center clinical trials is needed to accelerate its development and incorporation into clinical practice.

Omacetaxine mepesuccinate in chronic myeloid leukemia.

INTRODUCTION: Homoharringtonine (HHT) and other alkaloid esters were originally isolated from the Cephalotaxus evergreen tree and have been used in traditional Chinese medicine since the 1970s to treat a variety of malignancies. Although HHT was investigated for the treatment of chronic myeloid leukemia (CML) in the 1990s with good results, the advent of BCR-ABL1 tyrosine kinase inhibitors (TKIs) at that time rapidly established a new standard of care for CML. Omacetaxine mepesuccinate is a semisynthetic derivative of HHT with known clinical activity in relapsed or refractory CML following TKI therapy. AREAS COVERED: In this review, we summarize the biologic effects of HHT and its derivative, omacetaxine, in CML. Additionally, we analyze the concepts learned from the early trials using these drugs. Data from clinical trials resulting in drug approval are also reviewed. EXPERT OPINION: Omacetaxine has a clear role in the CML armamentarium for patients in chronic and accelerated phase who have failed or were intolerant to two or more TKIs.

Mechanism of action and clinical activity of tasquinimod in castrate-resistant prostate cancer.

Castrate-resistant prostate cancer (CRPC) is a disease where survival is poor and treatment is challenging. Over the past 3 years, significant advances in the field have been made with US Food and Drug Administration approval of new drugs for patients with CRPC. However, despite the presence of new approved drugs such as enzalutamide, abiraterone, sipuleucel-T, cabazitaxel, and alpharadin, there is still an unmet need for novel agents with different mechanisms of action to target CRPC. Based on earlier studies demonstrating therapeutic potential of a quinoline-3-carboxamide agent roquinimex as an anticancer drug, efforts were directed to identify other useful members in this class. Tasquinimod is a second-generation quinoline-3-carboxamide agent that is currently in final stages of clinical development as a treatment for CRPC. The preclinical studies of tasquinimod have formed the basis for its success as an antiangiogenic and immunomodulatory agent in this disease. Tasquinimod is an orally available agent that has shown efficacy and favorable safety profile as deduced by the results of Phase I and II clinical trials of this drug in prostate cancer. The place of tasquinimod in the treatment of CRPC patients is currently under examination in an ongoing Phase III clinical trial. In this review, we will discuss tasquinimod, starting from its discovery and current knowledge on potential mechanisms of action to its clinical potential in CRPC.

Genetics on a WHIM.

We initially described the WHIM syndrome based on the combination of Warts, Hypogammaglobulinaemia, Infections and Myelokathexis (neutrophil retention in the bone marrow). Translational research led to the discovery that this rare immunodeficiency disease is caused by a heterozygous mutation in the CXCR4 gene. Recently, Plerixafor has been suggested as a treatment for WHIM syndrome due to its efficacy as a CXCR4 antagonist, closing the translational research loop. In this review, we will focus on the clinical manifestations, pathophysiology, diagnosis and possible therapies for this rare entity.

The use of low-dose protracted oral clofarabine in a patient with myelodysplastic syndrome after failing 5-azacitidine.

Patients with myelodysplastic syndrome who fail hypomethylating agents have a very short median survival and about 25% risk of disease transformation to acute myeloid leukemia. We report our experience with low-dose protracted oral clofarabine in one patient who achieved stable disease for more than two years after failing 5-azacitidine.

Myelodysplastic syndromes and autoimmune diseases--case series and review of literature.

Our objective was to recognize the association of autoimmune diseases (AD) in patients with myelodysplastic syndromes (MDS) and understand how this association could affect prognosis and management of both diseases. We describe our cohort of 10 patients and 34 patients reported in the English literature in addition to ten cohort studies. Interestingly, four cases showed improvement in AD after 5-azacitidine treatment. The mechanism(s) of the association between AD and MDS are discussed. Treatment could be targeted against AD, MDS or both, though based on recent reports, treating MDS with hypomethylating agents alone could improve the associated AD.

Detection of circulating tumor cells in cancers of biliary origin.

BACKGROUND: Circulating Tumor Cells (CTCs) have been described in malignancies of epithelial origin. In this study we examined the detection of CTCs using CellSearch assay in cholangiocarcinoma and gallbladder cancer. METHODS: The clinical outcomes and detection of CTCs were examined in sixteen patients with biliary cancer using the CellSearch assay. Stages of cancer, baseline demographic data and overall survival were evaluated. RESULTS: Thirteen patients had cholangiocarcinoma and three had gallbladder cancer. Using a cut off of two or more CTCs per 7.5 mL of blood, 3/13 cholangiocarcinoma and 1/3 gallbladder cancer patients had detectable CTCs. At 12 months of follow up from time CTC is drawn; 1/4(25%) of patients with positive CTC were alive while 6/12 (50%) of patients with negative CTC remained alive without a significant difference in survival between the two groups. CONCLUSIONS: Our finding that 25% of patients with cholangiocarcinoma and gallbladder cancer have two or more detectable CTCs/7.5 mL is the first report to our knowledge in this disease. Larger patient numbers are needed to determine the prognostic significance of finding CTCs in biliary cancer. Prospective validation of the role of CTC in advanced biliary cancer patients is on going.