Case of Immune Checkpoint Inhibitor Induced Myasthenia Gravis.

An 85-year-old man was diagnosed with hepatocellular carcinoma (HCC) and was initially treated with transarterial chemoembolization (TACE) and sorafenib. He was then switched to nivolumab and ipilimumab in view of sorafenib intolerance and disease progression. Subsequently, he developed dysphagia and generalized dyspnea culminating in hypercapnic respiratory failure requiring intubation. After an extensive workup, the etiology of his fluctuating respiratory issues was narrowed down to a likely neuromuscular process. Although antibodies to acetylcholine receptors (anti-AChR Ab) were negative, he was treated with high-dose steroids due to clinical concern for Immune Checkpoint Inhibitor (ICI) neurotoxicity. His recovery post immune suppression and absence of recurrence after ICI cessation suggested the possibility of this being an ICI neurotoxicity manifesting with myasthenic symptoms. Incidentally, he also had evidence of aseptic meningitis on cerebrospinal fluid analysis further strengthening this diagnosis. This case illustrates the importance of early recognition of ICI toxicity which will in turn lead to initiating treatments sooner and also decreasing the length of illness.

Emergence of Chronic Lymphocytic Leukemia During Admission for COVID-19: Cause or Coincidence?

Chronic lymphocytic leukemia (CLL) is the most common leukemia affecting the western adult population. While CLL is known to be a risk factor for morbidity and mortality from coronavirus disease 2019 (COVID-19), COVID-19 has not been shown to be a risk factor for the development of CLL. We report a case of a 55-year-old man who presented with COVID-19 pneumonia and developed overt CLL during hospitalization. Four other cases were culled from the literature. We discuss mechanistic possibilities for the unmasking of CLL in susceptible individuals with COVID-19.

Integrating Collaborative Learning and Competition in a Hematology/Oncology Training Program.

New educational methods and structures to improve medical education are needed to face the challenge of an exponential increase and complexity of medical knowledge. Collaborative learning has been increasingly used in education, but its use in medical training programs is in its infancy, and its impact is still unknown; the role of competition in education is more controversial. We introduced these pedagogical methods to the hematology/oncology fellowship program at the University of Arkansas for Medical Sciences to improve attendance and performance at didactic activities and different educational outcomes. One year after the adoption of these methods, the fellowship program has reached many of the expected goals from this intervention without the negative consequences of competition observed in younger learners. The most important conclusion of this project is that collaboration and cross-generational team work provide a healthy and effective learning environment and competition may not add further benefit. Analysis, interpretation, and discussion of our experience are provided. This study was approved by the University of Arkansas for Medical Sciences IRB as a low risk educational intervention not requiring a consent form.

Triaging referrals as part of hematology/oncology fellowship training.

We developed an integrative component of the consult rotation for fellows training in hematology/oncology. This component consisted of triaging all consults to the hematology/oncology service of the CAVHS during a 1-year period of time. The goals of the rotation were to improve timeliness of response to consultation requests, to gain experience in differential diagnosis of patients with potential hematologic/oncologic disorders through of such patients, review of decisions with attending physicians, and communication of such with the referring physician. The major benefits were that fellows integrated didactic learning into real-life clinical cases, selected patients for their continuity clinic to assure sufficient variety and complexity of cases, honed their communication skills, learned about referring and attending physicians' styles, and gained practice in clinical vignettes representative of cases they would be expected to see in clinical practice. Disadvantages were time involvement (approximately 2 h/day) and risks of over- or under-referrals. Administratively, there was a significant decline in the wait time for patients to be seen in the hematology/oncology service. In all, this elective is a valuable integrative experience of senior fellows, but may have less value for first year fellows.

Anti-prostate specific membrane antigen designer T cells for prostate cancer therapy.

BACKGROUND: Designer T cells are T lymphocytes engineered toward specific antibody-type membrane antigens through chimeric immunoglobulin-T-cell receptor (IgTCR) genes that have been used for adoptive cellular immunotherapy. We have extended this approach to prostate specific membrane antigen (PSMA) as a means to attack prostate cancer. METHODS: A chimeric anti-PSMA IgTCR gene was constructed based on an anti-PSMA monoclonal antibody, 3D8. Both T-cell lines and primary cultured human T lymphocytes were transduced with the chimeric anti-PSMA IgTCR construct and were analyzed for IgTCR expression, specific activation by PSMA, cytotoxicity against PSMA-expressing tumor cells in vitro, and retardation of tumor growth in an animal model. RESULTS: The IgTCR was incorporated into the TCR-CD3 complex and formed a functional chimeric complex. The IgTCR-modified T cells were specifically activated through the chimeric receptor with PSMA as measured by IL-2 production and increased CD25 expression and specifically lysed the PSMA-expressing prostate cancer cells in vitro as well as retarded tumor growth in an animal model. CONCLUSIONS: The anti-PSMA designer T cells exhibit an antibody-type specificity that can recognize PSMA expressing tumor cells in a MHC-independent fashion, resulting in T-cell activation, target cell lysis in vitro and inhibition of tumor growth in vivo.

The academic hematology-oncology firm:a model for postgraduate cancer education.

OBJECTIVE: To examine whether the introduction of a subspecialty firm system results in improving fellowship training in hematology and oncology. METHODS: A subspecialty firm in Hematology-Oncology was created to provide ambulatory and inpatient, primary, and subspecialty care. A survey was conducted of all fellows who trained in this firm while enrolled in an affiliated University subspecialty fellowship program. RESULTS: The survey showed a positive impact of the firm in improving trainee-patient relationships, achievement of educational goals, and clinical competency. CONCLUSIONS: Larger observational studies are needed to evaluate the full impact of this model on educational outcomes in cancer patients.