Lymphoma-associated acquired von Willebrand syndrome responsive to splenectomy: A case report.

A previously healthy 33-year-old female presented with a large hematoma over her right knee after kneeling. She was found to have pancytopenia and massive splenomegaly. Von Willebrand Factor (VWF) antigen level was 0.38 units/ml, ristocetin cofactor activity 0.13 units/ml, and VWF multimeric distribution was normal. Bone marrow examination revealed an indolent B-cell lymphoma. Diagnosis was consistent with acquired von Willebrand syndrome as an autoimmune epiphenomenon of a lymphoma. Diagnostic and therapeutic splenectomy under hemostatic coverage was performed. VWF antigen levels and activities immediately normalized postoperatively and remained within the normal range several months later. Splenic pathology confirmed hairy cell leukemia with a BRAF mutation.

Coagulation test understanding and ordering by medical trainees: Novel teaching approach.

Background: Coagulation testing provides a prime opportunity to make an impact on the reduction of unnecessary laboratory test ordering, as there are clear indications for testing. Despite the prothrombin time/international normalized ratio and activated partial thromboplastin time being validated for specific clinical indications, they are frequently ordered as screening tests and often ordered together, suggesting a gap in understanding of coagulation. Methods: Based on a needs assessment, we developed an online educational module on coagulation for trainees, incorporating education on testing cost, specificity, and sensitivity. Fifty participating resident physicians and medical students completed a validated premodule quiz, postmodule quiz after completion of the module, and a latent quiz 3 to 6 months after to assess longer-term knowledge retention. Trainees provided responses regarding their subjective laboratory test-ordering practices before and after module completion. Results: The median premodule quiz score was 67% (n = 50; range, 24%-86%) with an increase of 24% to a median postmodule quiz score of 91% (n = 50; range, 64%-100%). There was evidence of sustained knowledge acquisition with a latent quiz median score of 89% (n = 40; range, 67%-100%). Trainees were more likely to consider the sensitivity, specificity, and cost of laboratory investigations before ordering them following completion of the educational module. Conclusions: Using the expertise of medical educators and incorporating trainee feedback, we employed a novel approach to the teaching of coagulation to maximize its approachability and clinical relevance. We found sustained knowledge retention regarding coagulation and appropriate coagulation test ordering, and a subjective change to trainee ordering habits following participation in our educational intervention.

Improvement in Hematology Interprofessional Care: Simulation With an Emphasis on Collaboration.

Introduction: For many training programs, including hematology, there are limited structured opportunities to practice collaboration as a competency. Training is often limited to ad hoc interactions during clinical rotations. Accordingly, there is further need for immersive and standardized collaboration educational programs. This pilot study explored simulation for developing and assessing collaboration competency among hematology residents. Methods: Two standardized simulation center scenarios were developed that required residents to work in interprofessional teams. The objectives were to develop collaboration competence and confidence through experiential learning and facilitated reflection. Team members included education and simulation experts as well as hematology nurses as embedded participants. Case 1 presented a 72-year-old male with stage 4 lymphoma experiencing shortness of breath during a rituximab infusion. Case 2 presented a 68-year-old male who suffered a provoked pulmonary embolism. Both cases utilized a simulated clinic space. Pre, post, and 3-month questionnaires (self-assessed collaboration competency and simulation evaluation) were completed. Each session included structured debriefing with facilitated reflection focused on collaboration. Results: Seven senior hematology subspecialty residents participated. Despite residents entering the simulation cases with confidence in collaboration, higher collaboration confidence ratings were observed on postsimulation questionnaires (8.2 vs. 7.6 on a 10-point Likert scale). Residents demonstrated awareness of appropriate collaboration skills, but at times failed to implement knowledge into action. Facilitated reflection during the debrief helped residents critique their collaboration performance and develop improvement plans. Discussion: Simulation is a promising tool for teaching and assessing collaboration within hematology training.

Efficacy of Omalizumab in Indolent Systemic Mastocytosis.

BACKGROUND: Systemic mastocytosis (SM) comprises a heterogeneous group of disorders characterized by the proliferation of clonal mast cells in skin and various internal organs. Omalizumab is an established, labelled therapy for allergic asthma and chronic urticaria, but its experience in the efficacy of SM is limited. METHODS: A retrospective analysis of 6 patients diagnosed with indolent SM treated with omalizumab at St. Michael's Hospital between 2009 and 2018 is described. Reported frequency of anaphylaxis, baseline and follow-up tryptase levels, and SM-related symptoms were captured to measure the control of the disease. RESULTS: Of the 5 patients who had experienced unprovoked anaphylaxis prior to treatment with omalizumab, 3 had no further episodes of anaphylaxis following initiation of omalizumab, while the remaining 2 patients had milder multisystem reactions. Significant improvement in cutaneous symptoms was also observed. CONCLUSION: These data suggest that omalizumab provides benefit to patients with SM who remain highly symptomatic in spite of treatment with conventional therapies.

A case for consideration by apheresis practitioners: Melanoma and PD-1 inhibitor treatment in a patient with multiple relapses of immune thrombotic thrombocytopenic purpura.

Thrombotic Thrombocytopenic Purpura (TTP) is a rare life-threatening disease caused by ADAMTS-13 deficiency. Up to forty percent of patients with TTP relapse, and most relapse within eight years of their first presentation. This case report describes a patient with an aggressive course of TTP who subsequently developed metastatic melanoma while receiving prophylactic rituximab. Limited data exists regarding the potential for malignancy in patients receiving Rituximab for benign conditions. This is the first published case of melanoma in a TTP patient treated with rituximab. Melanoma treatment with PD-1 inhibitors is also associated with worsening of pre-existing autoimmune conditions. In this case, a splenectomy resulted in a durable remission despite treatment with PD-1 inhibitor.

Management of Polycythemia Vera: A Survey of Canadian Physician Practice Patterns.

BACKGROUND: The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV) allows for an earlier detection of masked PV. The literature is scarce about the clinical uptake of new diagnostic algorithms for PV. In a cohort of Canadian hematologists, we aimed to identify how the revised 2016 WHO diagnostic criteria of PV are being incorporated into hematology practice, and if the treatment of PV is comparable to the approaches outlined by the Canadian Myeloproliferative Neoplasm Group. MATERIALS AND METHODS: A cross-sectional survey of practicing Canadian hematologists/oncologists was distributed to active members of the Canadian Hematology Society using an online survey-distributing website. Univariate and multivariate analysis was performed. RESULTS: The survey was completed by 86 respondents in total. Only type of practice was associated with respondents offering aspirin to all patients with PV (P = .0009). Respondents who were aware of the Canadian Myeloproliferative Neoplasm Group guidelines were more likely to phlebotomize patients to a target hematocrit of < 45% irrespective of gender (P = .042). Younger practitioners were more likely to use age over 60 years as an indication for initiating cytoreductive therapy (P = .0006). Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism. CONCLUSION: The survey confirmed that heterogeneity of practice in diagnosis and management of PV among Canadian hematologists exists, suggesting that targeted education in specific segments of the PV treatment providers may result in wider adoption of the guidelines and diagnostic criteria.

Web-based Oncology Educational Tool for Medical Trainees on Oncology Rotation-Results of a Pilot Study.

Oncology education for post-graduate medical trainees is mostly clinic-based with didactic lectures. However, a 3-4-week rotation lacks full exposure to the vast field of oncology, resulting in an educational gap. We felt there is a need for a standard curriculum to educate trainees on common oncology topics and encourage self-directed learning. This study aims to improve knowledge of oncology in trainees through the use of an oncology educational tool (consisting of a handbook and website) that we developed and evaluated. Fifty-three post-graduate trainees (years 1, 2, and 3) consented to participate at the start of their oncology rotation. In phase I, four participants took part in a usability evaluation of the tool. In phase II, 39 trainees underwent a knowledge assessment with use of the tool. Baseline and post-intervention test results were compared using paired t tests. In the qualitative study (phase III), 10 trainees provided feedback on the updated tool and overall rotation experience. Issues identified from phase I were addressed prior to subsequent phases. Phase II analysis of complete sets of data found the mean post-intervention scores (9.44/10) were significantly higher (p < 0.001) than the mean baseline scores (7.47/10). In the qualitative study, feedback strongly supported the integration of the tool for improving knowledge of trainees. To our knowledge, this is the first study to show that an oncology educational tool for medical trainees improves oncology knowledge by providing a standard curriculum. Future work involves evaluating this tool to determine if effects are from the education tool or rotation experience.

Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review.

The serum-soluble interleukin-2 receptor (sIL-2r) level is considered an important diagnostic test and disease marker in hemophagocytic syndromes/hemophagocytic lymphohistiocytosis (HPS/HLH). However, this cytokine receptor is rarely measured in clinical practice and has been excluded from recent diagnostic/classification criteria such as the HScore and macrophage activation syndrome (MAS) 16. We performed a systematic scoping review of 64 articles (1975-2016) examining the clinical utility of sIL-2r in HPS/HLH. Twenty-two articles describe sIL-2r as a sensitive diagnostic marker for HLH, but only three distinct datasets actually address sensitivity. The original HLH-2004 Guidelines reported sensitivity of 93% and specificity of 100% for sIL-2r ≥ 2400, based on a pediatric dataset (n = 152) which is published for the first time in this review. Two pediatric studies reported sensitivity of 89% for sIL-2r ≥ 2400 in diagnosis of MAS complicating juvenile idiopathic arthritis (JIA) (n = 27) and 88% for secondary HLH in acute liver failure (n = 9). Twenty articles described sIL-2r as a dynamic marker of disease activity that falls with response to treatment, and 15 described high initial sIL-2r levels >10,000 U/mL as a poor prognostic marker. The ability of sIL-2r to distinguish between subtypes of HPS/HLH was inconsistent. This review confirms the importance of soluble IL-2r as a diagnostic and disease marker in HPS/HLH, but also reveals the need for more primary data about its performance characteristics, particularly in adults. More emphasis should be made in including this simple, inexpensive test in clinical practice and studies of HPS/HLH.

A case report of unusually long lag time between immunotactoid glomerulopathy (itg) diagnosis and diffuse large B-cell lymphoma (DLBCL) development.

BACKGROUND: Immunotactoid glomerulopathy (ITG) is a rare cause of proteinuria characterized by organized microtubular deposits in the glomerulus. ITG has been associated with underlying lymphoproliferative disorders and any renal impairment may be reversible with treatment of the concomitant hematologic malignancy. This case is the first reported in literature where diffuse large B cell lymphoma developed two years following the initial ITG diagnosis. CASE PRESENTATION: A 55-year-old woman with a history of well-controlled diabetes mellitus and thalassemia trait presented with proteinuria (830 mg/day) in 2010. Initially, she was managed with renin-angiotensin-aldosterone-system blockade. In 2012, the proteinuria worsened (4.3 g/day) and a renal biopsy showed immunotactoid glomerulopathy (Fig. 1). Despite extensive work up, no lymphoproliferative disorder was initially found. In January 2014, the patient presented with a soft-palate mass found on biopsy to be diffuse large B-cell lymphoma. She received 6 cycles of R-CHOP, 4 cycles of high dose methotrexate chemotherapy for CNS prophylaxis and 30 Gy of Intensity Modulated Radiation Therapy. Follow-up revealed complete remission of diffuse large B-cell lymphoma and resolution of proteinuria from the ITG. CONCLUSION: As we recognize that patients with ITG may develop hematopoietic neoplasms, close long-term monitoring is important. Moreover, treatment of the lymphoproliferative disorder can allow for complete remission of ITG.

Social Media Use Among Physicians and Trainees: Results of a National Medical Oncology Physician Survey.

PURPOSE: Cancer management requires coordinated care from many health care providers, and its complexity requires physicians be up to date on current research. Web-based social media support physician collaboration and information sharing, but the extent to which physicians use social media for these purposes remains unknown. The complex field of oncology will benefit from increased use of online social media to enhance physician communication, education, and mentorship. To facilitate this, patterns of social media use among oncologists must be better understood. METHODS: A nine-item survey investigating physician social media use, designed using online survey software, was distributed via e-mail to 680 oncology physicians and physicians in training in Canada. Responses were analyzed using descriptive statistics. RESULTS: A total of 207 responses (30%) were received; 72% of respondents reported using social media. Social media use was highest, at 93%, in respondents age 25 to 34 years and lowest, at 39%, in those age 45 to 54 years. This demonstrates a significant gap in social media use between younger users and mid- to late-career users. The main barrier to use was lack of free time. CONCLUSION: The identified gap in social media use between age cohorts may have negative implications for communication in oncology. Despite advancements in social media and efforts to integrate social media into medical education, most oncologists and trainees use social media rarely, which, along with the age-related gap in use, may have consequences for collaboration and education in oncology. Investigations to further understand barriers to social media use should be undertaken to enhance physician collaboration and knowledge sharing through social media.

Thrombotic microangiopathy in a patient with adult-onset Still's disease.

BACKGROUND: Since there are many disorders that can present with thrombotic microangiopathy (TMA), establishing a correct diagnosis is important to offer the most appropriate therapy. CASE REPORT: A 26-year-old woman was transferred to our hospital with fragmentation hemolytic anemia, thrombocytopenia, and acute kidney failure. History revealed that she was recently diagnosed with adult-onset Still's disease (AOSD) and received intraocular injections of bevacizumab to treat acute retinal artery occlusion. At our hospital, she underwent extensive investigations and was treated with high-dose steroids, hemodialysis, and therapeutic plasma exchange. For recurrent disease, she received a single dose of eculizumab. RESULTS: The patient's ADAMTS13 activity was normal and she had evidence of complement activation. Genetic testing identified a benign polymorphism in the C3 gene. Pathophysiology of TMA in AOSD is briefly discussed and an overview of the literature is presented. CONCLUSION: Work-up of a new fragmentation hemolytic anemia and thrombocytopenia should include careful review of past history, including medications, as well as relevant laboratory investigations with aim to establish a correct diagnosis. Occasionally, the correct diagnosis is not the obvious one and there could be multiple contributors to the pathogenesis. Establishing diagnosis is important for counseling patient on disease prognosis and to guide treatment.

Overcoming obstacles in accessing unfunded oral chemotherapy: physician experience and challenges.

PURPOSE: Previous studies have shown hematologists and medical oncologists may not accept the financial limits set by governing agencies on patient access to oral chemotherapy. The purpose of this study was to capture the methods physicians used to overcome barriers to accessing chemotherapeutic regimens for their patients. METHODS: A total of 640 medical oncologists and hematologists across Canada were surveyed using a 13-item Web-based survey tool. The survey was delivered by e-mail with three follow-up reminders. After a response period of 3 months, results were collated and analyzed with descriptive statistics. RESULTS: Of the 640 invitations, 568 were successfully delivered, and 183 responses were received (response rate, 32.0%). Among respondents, 101 treated solid malignancies (55.2%), 49 treated nonsolid malignancies (26.8%), and 33 treated both (18.0%). To overcome funding barriers, participating oncologists enrolled patients onto clinical trials (90.5%), used compassionate access programs (96.1%), and made special requests to government (91.8%). Other methods included writing false claims on forms to fit funding criteria for drugs (31.1%) and using leftover drug supplies (31.0%). Physicians felt their inability to obtain unfunded medications had a negative impact on their patients' clinical outcomes (56.0%) and psychosocial quality of life (73.0%). Only 28.5% of physicians contacted their governing body with concerns about oral chemotherapy funding. CONCLUSION: Canadian physicians use numerous methods to obtain unfunded oral chemotherapies, including falsifying claims on access forms and submitting special requests to government agencies. Further study is warranted to explore the disconnection between policymakers and physicians with regard to funding of oral chemotherapies.

Disseminated sporotrichosis in a patient with hairy cell leukemia treated with amphotericin B and posaconazole.

We describe a case of disseminated Sporothrix schenckii infection in a man with underlying hairy cell leukemia. The immunological defects associated with this malignancy, as well as the management of refractory sporotrichosis are reviewed.