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Background: An antithrombotic stewardship program was implemented to reduce IV DTI use and increase fondaparinux and direct oral anticoagulant (DOAC) use for suspected or confirmed Heparin-induced thrombocytopenia (HIT). Objectives: This study evaluated the impact of an antithrombotic stewardship program on IV DTI utilization in patients with HIT. Methods: A retrospective analysis of adults receiving IV DTIs or fondaparinux from July 2016 to July 2017 (pre-stewardship) and October 2017 to July 2019 (post-stewardship) was conducted. Results: The median duration of IV DTI administration was not significantly different in HIT-negative patients between the pre- and post-stewardship cohorts (1.6 days (25th percentile (p25), 75th percentile (p75):.5, 3.3) vs 1.7 days (p25, p75:.9, 3.9), P =.31). The median duration of IV DTI administration in HIT-positive patients was 9.9 days (p25, p75: 7.6, 21.0) pre-stewardship and 7.3 days (p25, p75: 4.8, 16.5) post-stewardship (P =.18). For HIT-positive patients, the time from HIT diagnosis to discharge was 12.8 days (p25, p75: 8.9, 24.9) and 9.2 days (p25, p75: 4.0, 18.1) in the pre- and post-stewardship cohorts, respectively (P =.07). Fondaparinux and DOAC prescribing rates were 40.7% and 62.2% in the pre- and post-stewardship cohorts, respectively (P =.09). The percentage of patients with no contraindications to IV DTI alternatives receiving these agents increased from 31.2% to 78.6% (P =.01) following stewardship implementation. Conclusions: Intravenous DTI alternative utilization increased significantly after stewardship implementation. Stewardship implementation was associated with a non-statistically significant trend towards decreased IV DTI utilization and decreased length of stay for HIT-positive patients. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency anemia (IDA) is a common cause of fatigue and impaired quality of life. The present study aimed to evaluate the impact of intravenous iron supplementation with ferric carboxymaltose (FCM) on fatigue, physical function, and general health among patients with IDA attending routine clinical care.Methods: This was a prospective, single arm, observational study of adult patients prescribed with intravenous FCM for the treatment of IDA during routine clinical care. We used Patient-Reported Outcomes Measurement Information System (PROMIS) instruments to evaluate fatigue (PROMIS Short Form v1.0 13a [FACIT-Fatigue]), general health status (PROMIS Scale v1.2), and physical function (PROMIS Short Form v2.0 4a) before and at 3 and 6 months after FCM treatment.Results: A total of 152 patients were enrolled. Mean age was 47.4 ± 16.0 years and 82.2% were female. Mean serum hemoglobin was 10.2 ± 1.4 g/dL at baseline. All patients were treated with at least one FCM dose at baseline, with 77.6% receiving a two-dose treatment course. The mean baseline FACIT-Fatigue score was 61.0 ± 9.0, improving significantly to 50.2 ± 9.5 at 3 months after FCM treatment. A minimum 5-point improvement, pre-defined as clinically meaningful, was seen in the FACIT-Fatigue, PROMIS Global Physical Health, Global Mental Health and PROMIS Physical Function scores for 72.7%, 52.8%, 41.7% and 39.8% of patients at 3 months (p < 0.0001 for each change from baseline), with statistically significant improvement continuing at 6 months. Mean serum hemoglobin was significantly increased at both 3 and 6 months (12.8 g/dL [N = 44] and 12.4 g/dL [N = 54], respectively).Conclusion: IDA patients attending routine clinical practice reported substantial levels of fatigue and impairments in physical function and global health prior to intravenous iron treatment. Patients experienced significant improvements in fatigue symptoms, physical function, and global health at 3 months after treatment with FCM, which were sustained at 6 months. [ABSTRACT FROM AUTHOR]

Hemostatic and antithrombotic agents are high‐risk medications associated with high cost. The importance of anticoagulation stewardship has been recently highlighted by national organizations, but hemostatic stewardship programs remain underutilized. Several established hemostatic and/or antithrombotic stewardship programs have demonstrated a significant impact on the quality and cost of care provided to patients receiving these therapies. This review provides a comprehensive toolkit for development and implementation of combined hemostatic and antithrombotic stewardship programs. [ABSTRACT FROM AUTHOR]

Cutaneous T cell lymphomas (CTCL) comprise of a heterogeneous group of non-Hodgkin lymphomas derived from skin-homing T cells. Variation in clinical presentation and lack of definitive molecular markers make diagnosis especially challenging. The biology of CTCL remains elusive and clear links between genetic aberrations and epigenetic modifications that would result in clonal T cell expansion have not yet been identified. Nevertheless, in recent years, next generation sequencing (NGS) has enabled a much deeper understanding of the genomic landscape of CTCL by uncovering aberrant genetic pathways and epigenetic dysregulations. Additionally, single cell profiling is rapidly advancing our understanding of patients-specific tumor landscape and its interaction with the surrounding microenvironment. These studies have paved the road for future investigations that will explore the functional relevance of genetic alterations in the progression of disease. The ultimate goal of elucidating the pathogenesis of CTCL is to establish effective therapeutic targets with more durable clinical response and treat relapsing and refractory CTCL. [ABSTRACT FROM AUTHOR]

Prior to the introduction of rituximab, primary mediastinal B-cell lymphoma (PMBCL) had high rates of treatment failure with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), prompting the use of consolidative mediastinal radiation or more intensive chemotherapy regimens. Cure rates improved dramatically with rituximab, but mediastinal radiation was still commonly employed with R-CHOP. We performed a retrospective review of patients treated with R-CHOP alone without radiation for PMBCL. Of 43 patients with PMBCL, 16 received R-CHOP alone. High-risk factors included 56% with bulky disease, 75% with elevated LDH, 25% with SVC syndrome, and 13% with stage IV disease. Three-year progression-free survival (PFS) and overall survival (OS) were 93% and 100% respectively. These results suggest that R-CHOP alone has a high cure rate in PMBCL while avoiding the side effects of mediastinal radiation. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells in an inflammatory background. Patients are commonly diagnosed with HL in their 20s and 30s, and they present with supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in advanced-stage disease, HL is highly curable with combination chemotherapy, radiation, or combined-modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk-adapted approaches have helped de-escalate therapy in low-risk patients while intensifying treatment for higher risk patients. Even patients who are not cured with initial therapy can often be salvaged with alternate chemotherapy combinations, the novel antibody-drug conjugate brentuximab, or high-dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death-1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL. Alternate donor sources and reduced-intensity conditioning have made allogeneic hematopoietic stem cell transplantation a viable option for more patients. Future research will look to integrate novel strategies into earlier lines of therapy to improve the HL cure rate and minimize long-term treatment toxicities. CA Cancer J Clin 2018;68:116-132. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background. Histoplasmosis-associated hemophagocytic lymphohistiocytosis (HLH) is a relatively rare disorder for which data are limited regarding optimal treatment and clinical outcomes in adults. We describe the clinical features, treatment, and outcomes of patients with histoplasmosis-associated HLH at our institution. Methods. We performed a retrospective chart review of all inpatients at Parkland Hospital diagnosed with HLH associated with Histoplasma capsulatum from 2003 to 2013. Results. Eleven cases of histoplasmosis-associated HLH over this time period were identified. Nine of eleven cases were males (82%). Nine of these patients had human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), 1 was a renal transplant patient on immunosuppressants, and the other had no documented immunocompromise. The most common HLH criteria were splenomegaly (n = 10), fever (n = 10), and ferritin >500 ng/dL (n = 9). Urine Histoplasma antigen was positive in every patient tested (n = 9 of 9), and most antibodies for Histoplasma were positive if checked (n = 4 of 5). A majority of patients received liposomal amphotericin B (n = 9) with an average treatment duration of 11 days, and 5 patients also received prednisone, intravenous immunoglobulin (IVIG), or both. Overall, 5 patients died within 30 days (45.5%), and 7 patients died within 90 days (63.6%). Of the 5 patients that received immunosuppression, 4 died (80%), whereas in the group not given additional immunosuppression (n = 5), 2 died (40%). Conclusions. Histoplasmosis-associated HLH among adults is a lethal disease of highly immunocompromised patients, especially patients with HIV/AIDS. Clinical features such as splenomegaly, elevated ferritin, and cytopenias should prompt evaluation for HLH in this population. Further data are needed to define the role of immunosuppression, IVIG, and highly active antiretroviral therapy in treating this condition. [ABSTRACT FROM AUTHOR]

Metastatic esophageal cancer is incurable with 5-year survival rates of under 5% using currently available therapeutic strategies. Palliative chemotherapy with cisplatin- and 5-fluorouracil (5FU)-based regimens remains the standard of care for patients with recurrent unresectable or metastatic esophageal cancer. Upfront cisplatin-based regimens are poorly tolerated in some patient groups and, for patients with recurrent disease after platinum-based therapies, there is a need for an alternate efficacious regimen without significant toxicities. The combination of docetaxel and irinotecan is an active regimen in this disease and has been investigated in several phase II trials. Weekly dosing of chemotherapy is preferred over a once every 3 weeks regimen on account of comparable efficacy and improved toxicity profile. Future directions include investigation of pharmacogenomic treatment assignment, particularly as irinotecan appears to be active in tumors with high ERCC1 expression, which tend to be resistant to cisplatin. Combinations with biologics such as bevacizumab and cetuximab, which have shown additive benefit with other cytotoxic combinations, are also of interest for future study. [ABSTRACT FROM AUTHOR]

Metastatic esophageal cancer is incurable with 5-year survival rates of under 5% using currently available therapeutic strategies. Palliative chemotherapy with cisplatin- and 5-fluorouracil (5FU)-based regimens remains the standard of care for patients with recurrent unresectable or metastatic esophageal cancer. Upfront cisplatin-based regimens are poorly tolerated in some patient groups and, for patients with recurrent disease after platinum-based therapies, there is a need for an alternate efficacious regimen without significant toxicities. The combination of docetaxel and irinotecan is an active regimen in this disease and has been investigated in several phase II trials. Weekly dosing of chemotherapy is preferred over a once every 3 weeks regimen on account of comparable efficacy and improved toxicity profile. Future directions include investigation of pharmacogenomic treatment assignment, particularly as irinotecan appears to be active in tumors with high ERCC1 expression, which tend to be resistant to cisplatin. Combinations with biologics such as bevacizumab and cetuximab, which have shown additive benefit with other cytotoxic combinations, are also of interest for future study. [ABSTRACT FROM AUTHOR]

The article presents a case study of a woman having warm autoimmune hemolytic anemia who was treated using azathioprine.

Abstract: Medical diagnosis and therapy often rely on laboratory testing. We observed mistaken testing in evaluations for hemophagocytic lymphohistiocytosis (HLH) that led to delays and adverse outcomes. Physicians were mistakenly ordering interleukin-2 and quantitative natural killer cell flow cytometry, rather than soluble interleukin 2 receptor (sIL2R) or qualitative natural killer functional tests in the evaluation of patients suspected to have HLH.We initiated a prospective quality improvement project to reduce mistaken testing, reduce delays in correct testing due to mistaken ordering, and improve HLH evaluations. This consisted of provider education, developing an evaluation algorithm, and ultimately required systems interventions such as pop-ups and removal of the mistaken tests from the electronic ordering catalog.Active education reduced mistaken testing significantly in HLH evaluations from baseline (73.3% vs 33.3%, P = .003, relative risk reduction (RRR) 54.5%), but failed to meet the pre-specified RRR cutoff for success (70%). Education alone did not significantly reduce the proportion of HLH evaluations with delays in sIL2R testing (23.3% vs 7.4%, P = .096). Mistaken testing increased after the active intervention ended (33.3% vs 43.5%, P = .390, with RRR 40.7% from baseline. Mistaken test removal was successful: mistaken testing dropped to 0% (P < .001, RRR 100%), saved $14,235 yearly, eliminated delays in sIL2R testing from mistaken testing (23.3% vs 0%, P = .008), and expedited sIL2R testing after admission for HLH symptoms (14.6 days vs 3.8 days, P = .0012). These data show systems controls are highly effective in quality improvement while education has moderate efficacy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction : The newest intravenous (IV) iron products show an improved safety profile over predecessors, allowing for the rapid administration of relatively high doses. Ferric derisomaltose (FDI; also known as iron isomaltoside), ferric carboxymaltose (FCM), and ferumoxytol (FER), are successful treatments for iron deficiency (Europe; FDI and FCM) and iron deficiency anemia (US; FDI, FCM, and FER). Areas covered : This review focusses on the chemistry and structure of FDI, FCM, and FER, and on three key aspects of IV iron safety: (1) hypersensitivity; (2) hypophosphatemia and sequelae; (3) cardiovascular safety. Expert opinion : Although the safety of modern IV iron has improved, immediate infusion reactions and the development of hypophosphatemia must be appreciated and recognized by those who prescribe and administer IV iron. Immediate infusion reactions can occur with any IV iron and are usually mild; severe reactions - particularly anaphylaxis - are extremely rare. The recognition and appropriate management of infusion reactions is an important consideration to the successful administration of IV iron. Severe, persistent, hypophosphatemia is a specific side effect of FCM. No cardiovascular safety signal has been identified for IV iron. Ongoing trials in heart failure will provide additional long-term efficacy and safety data.

Immune checkpoint inhibitors (ICIs) are the standard of care for the treatment of several cancers. While these immunotherapies have improved patient outcomes in many clinical settings, they bring accompanying risks of toxicity, specifically immune-related adverse events (irAEs). There is a need for clear, effective guidelines for the management of irAEs during ICI treatment, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of single and combination ICI irAEs and ultimately developed evidence- and consensus-based recommendations to assist medical professionals in clinical decision-making and to improve outcomes for patients., Competing Interests: Competing interests: PAA—Contracted research: Bristol-Myers Squibb, Roche, Array; Consulting fees: Bristol-Myers Squibb, Roche, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, Medimmune, Sindax, AstraZeneca, Sun Pharma, Sanofy, Idera, Ultimovacs, Sandox, Immunocore, 4sc, Alkermes, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron; Travel support: MSD. JRB—Contracted research: AstraZeneca, Bristol-Myers Squibb, Genentech/Roche, Merck, RAPT Therapeutics, Inc, Revolution Medicines; Consulting fees: Amgen, Bristol-Myers Squibb, Genentech/Roche, Eli Lilly, GlaxoSmithKline, Merck, Sanofi, Regeneron; Data and safety monitoring board/committees: GlaxoSmithKline, Sanofi. JB—Partner consulting fees: AstraZeneca, Merck, Roche, Pfizer, Lilly, Daiichi, Seattle Genetics, Novartis. LCC—Consulting fees: AbbVie; Contracted research: Bristol-Myers Squibb, Merck, EMD Serono, Alkermes, Iovance, Merrimack, National Cancer Institute. DEG—Consulting fees: Samsung Bioepis, Catalyst Pharmaceuticals, Bristol-Myers Squibb Steering Committee, G1 Therapeutics; Contracted research: AstraZeneca, BerGenBio, Karyopharm, Bristol-Myers Squibb Steering Committee; Ownership interest: Gilead. DBJ—Consulting fees: Bristol-Myers Squibb, Catalyst Biopharma, Iovance, Jansen, Merck, Novartis, Oncosec; Contracted research: Bristol-Myers Squibb, Incyte. MEL—Contracted research: Veloce, US Biotest, Lutris, Paxman, Novocure Inc; Grant funding: National Cancer Institute Cancer Center support grant P30 CA008748, National Institute of Arthritis and Musculoskeletal and Skin Diseases grant U01AR0775; Royalty: Legacy Healthcare Services, Apricity Health, Azitra, Inc, Deciphera, Galderma Research and Development, Johnson and Johnson, NCODA, Novocure Inc, Kyowa Kirin Inc, Loxo, Merck Sharp and Dohme Corporation, Janssen Research & Development, Menlo Therapeutics, Novartis Pharmaceuticals Corporation, QED Therapeutics, F. Hoffmann-La Roche AG, Amgen Inc, AstraZeneca Pharmceuticals, Genentech Inc, Seattle Genetics, Lutris, Paxman Coolers, OnQuality Pharmaceuticals Ltd, Takeda Millenium. JN—Consulting fees: AstraZeneca, Bristol-Myers Squibb, Merck, Roche/Genentech; Contracted research: AstraZeneca, Merck; Non-CME services: Merck, Bristol-Myers Squibb, AstraZeneca. M-AP—Consulting fees: AbbVie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Kite/Gilead, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda; Contracted research: Incyte, Kite/Gilead and Miltenyi Biotec; Ownership interest: NexImmune Member, DSMBs for Cidara Therapeutics, Servier and Medigene. IP—Consulting fees: Merck, Amgen; Ownership interest: Celldex; Partner ownership: Celldex. BDS—Consulting fees: Kite/Gilead, Juno/Celgene; Contracted research: ADC Therapeutics; NPI: 1215164884. SPS—Consulting fees: Takeda, GSK, Kura, Celgene, Daiichi-Sankyo. DS—Scientific advisory board: Allergan, Alimera, Biogen. JAS—Consulting fees: Array, Nektar, Bristol-Myers Squibb, Iovance, Curis; Contracted research: Bristol-Myers Squibb, Corvus, Caltera. HA-S, FBC, MSE, LH, EH, GAM, MN, RS, MT—Nothing to disclose. SITC staff: SMW—Shares owned: Pacific Biosciences of California Inc, Editas Medicine. EG, AK, BL, LL—Nothing to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Medicare Part B payment methods incentivize the use of more expensive injectable and infused drugs. We examined prescribing patterns in the context of intravenous (IV) iron, for which multiple similarly safe and efficacious formulations exist, with wide variations in price., Study Design: We conducted a retrospective cohort analysis of IV iron utilization and payment in the Medicare population between 2015 and 2017., Methods: This analysis used a national, random 20% sample of Medicare fee-for-service beneficiaries with Part B claims for IV iron between January 2015 and December 2017-a period before, during, and after a national shortage of iron dextran. This sample included 66,710 Medicare fee-for-service beneficiaries with at least 1 Part B claim for IV iron., Results: The greatest increase in utilization occurred in the most expensive iron formulation, ferric carboxymaltose; its market share rose from 27.4% of use in 2015 to 47.7% in 2017. The use of a less expensive formulation, iron dextran, decreased from 26.7% to 18.7% over the same period. An alternative payment model in Maryland hospitals was associated with markedly less utilization of ferric carboxymaltose, accounting for 4.7% of IV iron utilization in Maryland hospitals., Conclusions: There was an increase in the dispensing of a higher-priced IV iron formulation associated with a shortage of a less expensive drug that persisted once the shortage ended. These findings in IV iron have broader implications for Part B drug payment policy because the price of the drug determines the physician and health system payment.

Systems-based hematology is dedicated to improving care delivery for patients with blood disorders. First defined by the American Society of Hematology in 2015, the idea of a systems-based hematologist arose from evolving pressures in the health care system and increasing recognition of opportunities to optimize the quality and cost effectiveness of hematologic care. In this review, we begin with a proposed framework to formalize the discussion of the range of initiatives within systems-based hematology. Classification by 2 criteria, project scope and method of intervention, facilitates comparison between initiatives and supports dialogue for future efforts. Next, we present published examples of successful systems-based initiatives in the field of hematology, including efforts to improve stewardship in the diagnosis and management of complex hematologic disorders (eg, heparin-induced thrombocytopenia and thrombophilias), the development of programs to promote appropriate use of hematologic therapies (eg, blood products, inferior vena cava filters, and anticoagulation), changes in care delivery infrastructure to improve access to hematologic expertise (eg, electronic consultation and disorder-specific care pathways), and others. The range of projects illustrates the broad potential for interventions and highlights different metrics used to quantify improvements in care delivery. We conclude with a discussion about future directions for the field of systems-based hematology, including extension to malignant disorders and the need to define, expand, and support career pathways., (© 2020 by The American Society of Hematology.)

Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).

The approval of several new clotting factor concentrates and anticoagulation antidotes has resulted in increased complexity and cost of care. A multidisciplinary hemostatic stewardship program is essential to optimize utilization of these resources. This article summarizes the authors' approach to the stewardship of clotting factor concentrates and anticoagulation antidotes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (irAEs). Methods to obtain real-time multidisciplinary input for irAEs that require subspecialist care are unknown. This study aimed to determine whether a virtual multidisciplinary immune-related toxicity (IR-tox) team of oncology and medicine subspecialists would be feasible to implement, be used by oncology providers, and identify patients for whom multidisciplinary input is sought., Patients and Methods: Patients treated with ICIs and referred to the IR-tox team in August 2017 through March 2018 were identified. Feasibility was defined as receipt of electronic referrals and provision of recommendations within 24 hours of referral. Use was defined as the proportion of referring providers who used the team's recommendations, which was determined through a postpilot survey. Demographics and tumor, treatment, and referral data were collected. Patient features and irAE associations were analyzed., Results: The IR-tox team was found to be feasible and used: 117 referrals from 102 patients were received in 8 months, all providers received recommendations within 24 hours, 100% of surveyed providers used the recommendations, and 74% changed patient management based on IR-tox team recommendations. Referrals were for suspected irAEs (n=106; 91%) and suitability to treat with ICIs (n=11; 10%). In referred patients, median age was 64 years, 54% were men, 13% had prior autoimmunity, and 46% received ICI combinations versus monotherapy (54%). The most commonly referred toxicities were pneumonitis (23%), arthritis (16%), and dermatitis (15%); 15% of patients had multisystem toxicities. Multiple referrals were more common in those treated with combination ICIs (odds ratio [OR], 6.0; P=.035) or with multisystem toxicities (OR, 8.1; P=.005). The IR-tox team provided a new multidisciplinary forum to assist providers in diagnosing and managing complex irAEs. This model identifies educational and service needs, and patients with irAEs for whom multidisciplinary care is most sought., Conclusions: A virtual multidisciplinary toxicity team for irAEs was a feasible and used service, and facilitated toxicity identification and management.