Progressive Global Ataxia With Sensory Changes as a Paraneoplastic Syndrome in a Patient With Chromophobe Renal Cell Carcinoma.

Paraneoplastic syndromes (PNS) are rare and can be challenging to diagnose and treat. The uniqueness of PNS lies in the complexity of presentation, the importance of early diagnosis, and the role of multidisciplinary care in managing those patients to mitigate long-term neurologic complications. We describe a patient with metastatic renal cell carcinoma who presented with a complex constellation of neurological symptoms (progressive global ataxia and sensory changes) that did not resolve following nephrectomy. While complete resolution of symptoms was not achieved, he did have stabilization of his neurologic decline with the initiation of cancer-directed therapies.

Pembrolizumab in a Patient with Treatment-Naïve Unresectable BRAF-Mutation Negative Anaplastic Thyroid Cancer.

Immune check point inhibitor (ICI) therapy can be a potentially effective salvage treatment for anaplastic thyroid cancer (ATC) with progression despite standard of care therapies. We report a case of unresectable treatment-naïve ATC showing a dramatic and durable response to first-line pembrolizumab therapy. A 69-year-old male presented with a large, right-sided neck mass associated with compressive symptoms. A neck ultrasound showed a large, right-sided, and highly suspicious thyroid nodule. A fine needle aspiration (FNA) biopsy revealed tumor cells consistent with ATC that were positive for PD-L1, with an expression score of >95% and negative for the BRAF V600E mutation. Imaging studies were negative for distant metastases. The disease was declared surgically inoperable, and the patient declined chemotherapy/radiation therapy (XRT), but agreed to ICI therapy with intravenous pembrolizumab 200 mg every three weeks. The patient has received 25 doses of pembrolizumab to date, with rapid resolution of symptoms and a significant reduction in tumor size. He remains alive without disease progression 18 months since initial diagnosis.

Warm Autoimmune Hemolytic Anemia Associated With Asymptomatic SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resultant coronavirus disease 2019 (COVID-19) are associated with several hematologic abnormalities, including immune thrombocytopenia, antiphospholipid syndrome, and autoimmune hemolytic anemia (AIHA). Initial case reports suggested immune dysregulation to be the underlying etiology of SARS-CoV-2-associated AIHA, as all reported cases involved patients with moderate to severe COVID-19, many of whom had underlying lymphoproliferative disorders. More recently, AIHA has been reported in patients with mildly symptomatic SARS-CoV-2 infection. Here, we detail a patient with asymptomatic SARS-CoV-2 infection who presented with severe, symptomatic anemia. Workup was consistent with warm autoimmune hemolytic anemia (WAIHA) secondary to SARS-CoV-2 infection.

Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration.

Chronic lymphocytic leukemia (CLL) patients who develop Hodgkin lymphoma (HL) have limited survival. No current therapeutic standard of care exists. We conducted a multi-center retrospective study of patients with Hodgkin Transformation (HT) of CLL. Clinicobiologic characteristics, treatment type, and survival outcomes were analyzed and compared with historic case series. Ninety-four patients were identified. Median age at HT was 67 years (range, 38-85). Median time from CLL diagnosis to HT was 5.5 years (range, 0-20.2). Prior to HT, patients received a median of 2 therapies for CLL (range, 0-12). As initial therapy for HT, 61% (n=62) received ABVD-based regimens (adriamycin, bleomycin, vinblastine, and dacarbazine). Seven (7%) patients received hematopoietic cell transplantation (HCT) while in first complete remission (CR1). The median number of treatments for HT per patient was 1 (range, 0-5) with 59 (61%) patients only receiving one line of therapy. After HT, patients had a median follow-up of 1.6 years (range, 0-15.1). Two-year overall survival (OS) after HT diagnosis was 72% (95%CI 62-83%). The patients who received standard ABVD-based therapy had a median OS of 13.2 years. Although limited by small sample size, the patients who underwent HCT for HT in CR1 had a similar 2-year OS (n=7; 67%) compared to patients who did not undergo HCT for HT in CR1 (n=87; 72%; p=0.46). In this multi-center study, HT patients treated with ABVD-based regimens had prolonged survival supporting the use of these regimens as standard of care for these patients.

Practice Patterns in the Diagnosis and Treatment of Polycythemia Vera in the Post-JAK2 V617F Discovery Era.

Polycythemia vera (PV) is an acquired clonal hematopoietic stem cell disorder characterized by an overproduction of red blood cells, white blood cells, and platelets; thrombotic and hemorrhagic complications; and an increased risk of transformation to myelofibrosis and acute leukemia. In 1967, the Polycythemia Vera Study Group proposed the optimal approach to diagnosis and treatment of PV, and in 2002, investigators from Johns Hopkins University School of Medicine surveyed the practice patterns of hematologists as they pertained to PV. Since this survey, the JAK2 V617F mutation was discovered, leading to a new era of discovery in the disease pathogenesis, diagnosis, and classification and treatment of PV. Our objective was to survey hematologists in the diagnosis and treatment of PV in the modern, post-JAK2 V617F discovery era. An anonymous 17-question survey was emailed to members of the Myeloproliferative Neoplasm (MPN) Research Foundation database and Aplastic Anemia and MDS International Foundation. A total of 71 surveys were used in the analysis. Diagnostic testing varied according to the respondent's clinical experience and practice type. In addition, there were marked differences in target hematocrit and platelet count among those surveyed. There continue to be variations in diagnosis and treatment of PV despite WHO guidelines and the JAK2 discovery. US-based guidelines for MPNs are needed to create consistency in the management of PV and other MPNs.

Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort.

The BCR-ABL1-negative myeloproliferative neoplasms (MPN) share an increased risk of thrombotic and hemorrhagic complications. Risk factors for hemorrhage are less well defined than those for thrombosis. Because patients with CALR mutations have higher platelet counts compared to JAK2 V617F-mutated patients, bleeding rates may be increased in this group. Our aim was to retrospectively evaluate whether acquired von Willebrand disease (AvWD), thrombocytosis, mutational status, or treatment history are associated with bleeding in a cohort of MPN patients. Using an electronic database, MPN patients seen between 2005 and 2013 were retrospectively identified using ICD-9 codes and billing records. A bleeding event was defined as one that was identified in the medical record and graded based on the Common Terminology Criteria for Adverse Event (CTCAE) version 4.0. Among 351 MPN patients, 15.6 % experienced 64 bleeding event types. There was no association of bleeding with mutational status, gender, MPN subtype, aspirin use, prior thrombosis, or platelet count at presentation. There was an association between bleeding and older age at diagnosis. aVWD was identified in six patients. In this single-center retrospective study, bleeding events were identified in 15 % of patients, and associated with older age at diagnosis. aVWD was rarely tested for in this cohort.

PAX3/7 expression coincides with MyoD during chronic skeletal muscle overload.

Paired box (Pax) proteins 3 and 7 are key determinants for embryonic skeletal muscle development by initiating myogenic regulatory factor (MRF) gene expression. We show that Pax3 and 7 participate in adult skeletal muscle plasticity during the initial responses to chronic overload (< or =7 days) and appear to coordinate MyoD expression, a member of the MRF family of genes. Pax3 and 7 mRNA were higher than control within 12 h after initiation of overload, preceded the increase in MyoD mRNA on day 1, and peaked on day 2. On days 3 and 7, Pax7 mRNA remained higher than control, suggesting that satellite cell self-renewal was occurring. Pax3 and 7 and MyoD protein levels were higher than control on days 2 and 3. These data indicate that Pax3 and 7 coordinate the recapitulation of developmental-like regulatory mechanisms in response to growth-inducing stimuli in adult skeletal muscle, presumably through activation of satellite cells.