A phase 3b study of venetoclax and azacitidine or decitabine in an outpatient setting in patients with acute myeloid leukemia.

Venetoclax, a highly selective BCL-2 inhibitor, combined with hypomethylating agents (HMAs) azacitidine or decitabine, is approved for the treatment of newly diagnosed acute myeloid leukemia (ND AML) in patients who are ineligible to receive intensive chemotherapy. Previous clinical studies initiated venetoclax plus HMA in an inpatient setting owing to concerns of tumor lysis syndrome (TLS). This study (NCT03941964) evaluated the efficacy and safety of venetoclax plus HMA in a United States community-based outpatient setting in patients with ND AML (N = 60) who were treatment naïve for AML, ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at screening, and were deemed as appropriate candidates for outpatient initiation of venetoclax plus HMA by the investigator. Patients received venetoclax in combination with azacitidine (75 mg/m2) or decitabine (20 mg/m2) for up to 6 cycles during the study. With a median time on study of 18.3 weeks, the best response rate of composite complete remission was 66.7%, and the overall post-baseline red blood cell (RBC) and platelet transfusion independence rate was 55.0%, consistent with results of studies in which treatment was initiated in an inpatient setting. Key adverse events included nausea, anemia, thrombocytopenia, neutropenia, and white blood cell count decrease of any grade (≥50% of patients). The observed safety profile was generally consistent with that of venetoclax plus HMA observed in inpatient AML studies. With close monitoring, 2 cases of TLS were identified, appropriately managed, and the patients were able to continue study treatment. CLINICAL TRIALS REGISTRATION: This study is registered at ClinicalTrials.gov. The registration identification number is NCT03941964.

Lambert-Eaton myasthenic syndrome and merkel cell carcinoma.

Lambert-Eaton myasthenic syndrome (LEMS) is an antibody-mediated disorder of the neuromuscular junction that is most commonly diagnosed in association with small cell lung carcinoma (SCLC). Small cell lung carcinoma is histologically similar to the aggressive cutaneous neuroendocrine malignancy Merkel cell carcinoma (MCC). We provide a full report and longitudinal clinical follow-up of a case of LEMS occurring with MCC. We also review the literature on paraneoplastic syndromes associated with MCC and other nonpulmonary small cell carcinomas.

Chronic Lymphocytic Leukemia as an Unusual Cause of Rapid Airway Compromise.

Chronic Lymphocytic Leukemia (CLL) is the most prevalent form of non-Hodgkin's lymphoma (NHL) in Western countries predominantly affecting adults over the age of 65. CLL is commonly indolent in nature but can present locally and aggressively at extranodal sites. Although CLL may commonly present with cervical lymphadenopathy, manifestation in nonlymphoid regions of the head and neck is not well described. CLL causing upper airway obstruction is even more uncommon. We describe a case of a patient with known history of CLL and stable lymphocytosis that developed an enlarging lymphoid base of tongue (BOT) mass resulting in rapid airway compromise.

Rates of Microbiologically Diagnosed Infection and Pathogen Detection in Hematopoietic Stem Cell Transplant Patients.

Infections remain a significant cause of mortality in hematopoietic stem cell transplant patients. Evaluations of causes of infection are often unrevealing, and at some sites, increasing rates of antimicrobial resistance have been noticed. We performed a retrospective analysis of infection rates and microbiologic testing yield, or percent of tests ordered to diagnose an infection, in the first 100 days of 30 allogeneic and 56 autologous stem cell transplants performed at San Antonio Military Medical Center from July 2011 to April 2014. Blood stream infections were diagnosed in 11.6% with a yield of 6%. Urinary tract infections were diagnosed in 2.3% with a yield of 3%. Clostridium difficile infections were diagnosed in 9.3% and testing yield was 6%. Incidence of respiratory viruses was 5.8% with 4 rhinoviruses/enteroviruses and 1 influenza virus identified. One Proteus mirabilis urinary isolate was an extended spectrum beta-lactamase producer. Five patients, 13% of allogeneic and 4% of autologous patients, died within the first 100 days post-transplantation. History of bacteremia was present in 60% of patients who died; however, only one died due to a microbiologically diagnosed infection. Improved diagnostic tests and methods are needed to increase yield of detection of infection in hematopoietic stem cell transplant patients.