Cryptococcal Neoformans and Varicella Zoster Meningitis in a Patient With Selective Innate Immunodeficiency: A Case Report.

Cryptococcal neoformans (C. neoformans) and varicella-zoster (VZV) meningitis are opportunistic infections that are primarily seen in immunocompromised patients, including those with HIV, cancer, or receiving transplants. Despite treatment, infection in immunocompromised patients can be lethal, including those with T-cell dysfunction or deficiency. Whether innate immunodeficiencies also predispose to these infections remains less clear. Here, we report a case of disseminated C. neoformans and VZV meningitis in a young male with idiopathic hypereosinophilic syndrome and hypocomplementemia and no history of HIV infection, malignancy, or transplant. The patient presented with a pulsating headache, myalgia, joint pain, insomnia, night sweats, and subjective fever, along with clusters of vesicular lesions on his neck and back. A lumbar puncture and an MRI of the brain confirmed C. neoformans and VZV meningitis. Vesicular skin lesions proved to be VZV, and blood culture confirmed fungemia, suggesting disseminated disease. We investigated his medical history further to determine the underlying cause of his prior hypereosinophilia and current meningitis. The patient had idiopathic hypereosinophilia with high IgE levels, low complement levels, high rheumatoid factor levels, and an intermittent rash dating back two years, which had been treated intermittently with prednisone and hydroxyurea, with the most recent admission three weeks prior to this admission. Prior to admission, the patient had a peak absolute eosinophil count of 18.6 x103/uL. The patient was discharged on a daily dose of 60 mg of prednisone without hydroxyurea. In further evaluating his immune status, we found he was HIV-negative, with a normal CD4 count and high IgE. We also tested lymphocyte subsets and proliferation, which showed a low CD16/56 level, suggesting possibly reduced natural killer (NK) cell quantity. The patient responded well to acyclovir, amphotericin, and flucytosine therapy. After follow-up cerebrospinal fluid (CSF) and blood cultures were negative, the patient was discharged with fluconazole as maintenance therapy.

Outcomes of Tyrosine Kinase Inhibitors Maintenance Therapy with or without Allogeneic Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in First Complete Remission: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to compare outcomes of tyrosine kinase inhibitor (TKI) maintenance therapy with or without allogeneic hematopoietic stem cell transplantation (HSCT) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in first remission (CR1). A literature search was performed on PubMed, Cochrane, and Clinical trials.gov. After screening 1720 articles, 12 studies were included. Proportions and odds ratios (OR) with 95% confidence intervals (CI) were computed. I2 provides an estimate of the percentage of variability in results across studies that is due to real differences and not due to chance. Of 1039 patients, 635 (61%) had TKI alone and 404 (39%) patients had HSCT followed by TKI. At 3 years, a trend towards poor overall survival (OS; OR 0.67, 95% CI 0.39-1.15, I2 = 68%), (disease-free survival; OR 0.58, 95% CI 0.26-1.29, I2 = 76%), and higher relapse rate (RR; OR = 2.52, 95% CI = 1.66-3.83, I2 = 26%) was seen with TKI alone compared to HSCT-TKI. Although HSCT followed by TKI maintenance in Ph+ ALL has long been considered standard of care, the introduction of potent third-generation TKIs and bispecific T-cell engagers such as Blinatumomab has significantly improved outcomes while sparing the need for HSCT in newly diagnosed patients.

Multi-Database Description of Primary Splenic Diffuse Large B-Cell Lymphoma.

BACKGROUND/AIM: Stage I splenic diffuse large B-cell lymphoma (DLBCL) is rare and there are few data to guide management. We sought to further define prognosis and outcomes. MATERIALS AND METHODS: We utilized the Surveillance, Epidemiology, and End Results registry to identify patients with stage I splenic DLBCL diagnosed 1973-2013. Patients were divided into two cohorts based on the year of diagnosis (1983-2005; 2006-2013) as rituximab was approved by the U.S. Food and Drug Administration in 2006 for first-line treatment of DLBCL. RESULTS: Utilization of splenectomy decreased after the approval of rituximab (82% pre- versus 72% rituximab-era). Disease-specific and overall survival were greater with splenectomy [hazard ratio (HR)=0.57, p=0.04; and HR=0.66, p=0.03, respectively], but this benefit was only seen in the pre-rituximab cohort, not in the rituximab-era cohort. There was a trend toward improved overall survival with the introduction of rituximab (HR=0.75, p=0.054). CONCLUSION: Utilization of splenectomy for stage I splenic DLBCL has decreased with the introduction of rituximab without compromising outcomes.