Venetoclax is safe and tolerable as post-transplant maintenance therapy for AML patients at high risk for relapse.

Relapse is the most common cause of mortality in acute myeloid leukemia (AML) patients after allogeneic stem cell transplant (SCT). Post-SCT maintenance strategies that prevent relapse are desirable but must be well tolerated and convenient to administer. We hypothesized single agent venetoclax (ven) may be an effective maintenance therapy among high relapse risk patients.

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia.

Venetoclax+azacitidine is the standard of care for newly-diagnosed patients with acute myeloid leukemia (AML) for whom intensive chemotherapy is inappropriate. Efforts to optimize this regimen are necessary. We designed a clinical trial to investigate two hypotheses: i) higher doses of venetoclax are tolerable and more effective, and ii) azacitidine can be discontinued after deep remissions.

Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia.

Background: The time-limited combination of venetoclax and obinutuzumab (VenG) was established by the German CLL Study Group in the CLL14 trial for the upfront management of newly diagnosed chronic lymphocytic leukemia (CLL), showing a superior progression free survival benefit. The incidence of grade 3-4 neutropenia was reported in the range of 52.8%-57.

Getting Interdisciplinary Teams into the Field: Institutional Review Board Preapproval and Multi-Institution Authorization Agreements for Rapid Response Disaster Research.

This article describes an interdisciplinary community resilience research project and presents a case study that supports bringing researchers together before a disaster to develop plans, procedures, and preapproved Institutional Review Board (IRB) protocols. In addition, this article explains how researchers from various academic institutions and their federal agency partners can effectively collaborate by creating an IRB Authorization Agreement (IAA). Such preparations can support interdisciplinary rapid response disaster fieldwork that is timely, ethically informed, and scientifically rigorous.

Glasdegib plus low-dose cytarabine for acute myeloid leukemia: Practical considerations from advanced practitioners and pharmacists.

Objective: Acute myeloid leukemia (AML) is primarily a disease of older adults. These patients may not be candidates for intensive treatment, and there has been an ongoing need for treatment options for this group. We review the use of glasdegib, a hedgehog-pathway inhibitor available for use in combination with low-dose cytarabine (LDAC).

Letermovir prophylaxis through day 100 post transplant is safe and effective compared with alternative CMV prophylaxis strategies following adult cord blood and haploidentical cord blood transplantation.

We compared CMV outcomes of three prophylactic approaches used for CBT and haploidentical cord transplants from December 2009 through 2018: letermovir (n = 32) through day 100 post transplant, "valacyclovir day 100" (valacyclovir 2 g orally three times daily through day 100) (n = 60), and "valacyclovir hospital discharge" (valacyclovir 2 g orally three times daily through hospital discharge then acyclovir 800 mg twice daily) (n = 41). Through day 100, none in the letermovir group, six (10%) in the "valacyclovir day 100," and nine (22%) in the "valacyclovir hospital discharge" group required CMV directed treatment (p = 0.005 and 0.

Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia.

Venetoclax is approved for older untreated acute myeloid leukemia (AML) patients. Venetoclax was available prior to approval off-label. We assessed our single-institution off-label experience with venetoclax/azacitidine, comparing outcomes with a clinical trial cohort that administered this regimen at the same institution.

Oral Vancomycin Prophylaxis as Secondary Prevention Against Clostridioides difficile Infection in the Hematopoietic Stem Cell Transplantation and Hematologic Malignancy Population.

Clostridioides difficile infection (CDI) is a common complication in the hematopoietic stem cell transplantation (HSCT) and hematologic malignancy (HM) population. CDI is associated with increased hospital length of stay, health care and societal costs, morbidity, and mortality. Identifying strategies for secondary prevention of CDI is of extreme importance in the HSCT/HM population.

RVX-297, a BET Bromodomain Inhibitor, Has Therapeutic Effects in Preclinical Models of Acute Inflammation and Autoimmune Disease.

Bromodomain (BD) and extra-terminal domain containing proteins (BET) are chromatin adapters that bind acetylated histone marks via two tandem BDs, BD1 and BD2, to regulate gene transcription. BET proteins are involved in transcriptional reprogramming in response to inflammatory stimuli. BET BD inhibitors (BETis) that are nonselective for BD1 or BD2 have recognized anti-inflammatory properties in vitro and counter pathology in models of inflammation or autoimmune disease.

Clonality of neutrophilia associated with plasma cell neoplasms: report of a SETBP1 mutation and analysis of a single institution series.

A rare but well-known association between plasma cell neoplasms and neutrophilia is known to exist. Whether the neutrophilia is secondary to the plasma cell neoplasm or this convergence represents two independent clonal disorders is unclear. We reviewed five consecutive cases from a single institution over a 3-year period, applying molecular, cytogenetic and cytokine-profiling approaches to determine whether neutrophilia associated with plasma cell neoplasms represents a reactive or clonal process.

A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice.

Despite the benefit of statins in reducing cardiovascular risk, a sizable proportion of patients still remain at risk. Since HDL reduces CVD risk through a process that involves formation of pre-beta particles that facilitates the removal of cholesterol from the lipid-laden macrophages in the arteries, inducing pre-beta particles, may reduce the risk of CVD. A novel BET bromodomain antagonist, RVX-208, was reported to raise apoA-I and increase preβ-HDL particles in non-human primates and humans.

Leukemia/lymphoma-related factor regulates oligodendrocyte lineage cell differentiation in developing white matter.

Leukemia/lymphoma-related factor (LRF) is a zinc-finger transcription factor that regulates differentiation and oncogenesis in multiple tissues and cell lineages. The potential role for LRF in cells of the CNS has not been examined to date. This study shows prominent nuclear expression of LRF in diverse neuronal populations and in oligodendrocytes.

Reduced axonopathy and enhanced remyelination after chronic demyelination in fibroblast growth factor 2 (Fgf2)-null mice: differential detection with diffusion tensor imaging.

Chronic central nervous system demyelinating diseases result in long-term disability because of limited remyelination capacity and cumulative damage to axons. Corpus callosum demyelination in mice fed cuprizone provides a reproducible model of chronic demyelination in which the demyelinating agent can be removed to test modifications that promote recovery and to develop noninvasive neuroimaging techniques for monitoring changes in myelin and axons. We used the cuprizone model in mice with genetic deletion of fibroblast growth factor 2 (Fgf2) to determine the impact of FGF2 on axon pathology and remyelination after chronic demyelination.

Rostrocaudal analysis of corpus callosum demyelination and axon damage across disease stages refines diffusion tensor imaging correlations with pathological features.

Noninvasive assessment of the progression of axon damage is important for evaluating disease progression and developing neuroprotective interventions in multiple sclerosis patients. We examined the cellular responses correlated with diffusion tensor imaging-derived axial (lambda(parallel)) and radial (lambda(perpendicular)) diffusivity values throughout acute (4 weeks) and chronic (12 weeks) stages of demyelination and after 6 weeks of recovery using the cuprizone demyelination of the corpus callosum model in C57BL/6 and Thy1-YFP-16 mice. The rostrocaudal progression of pathological alterations in the corpus callosum enabled spatially and temporally defined correlations of pathological features with diffusion tensor imaging measurements.

Multiple genes influence BMI on chromosome 7q31-34: the NHLBI Family Heart Study.

The National Heart, Lung, and Blood Institute Family Heart Study (FHS) genome-wide linkage scan identified a region of chromosome 7q31-34 with a lod score of 4.9 for BMI at D7S1804 (131.9 Mb).

Valproic acid-carbapenem interaction: report of six cases and a review of the literature.

Aim: To evaluate the drug interactions between valproic acid (VPA) and carbapenem antibiotics.

Methods: The effects of concurrent use of VPA and carbapenem antibiotics were evaluated in a retrospective observational study of hospitalized adults. Patients receiving both VPA and a carbapenem with at least two plasma VPA concentrations serially measured prior to, during, and/or after this combined treatment were included.

ABCA12 maintains the epidermal lipid permeability barrier by facilitating formation of ceramide linoleic esters.

Harlequin ichthyosis is a congenital scaling syndrome of the skin in which affected infants have epidermal hyperkeratosis and a defective permeability barrier. Mutations in the gene encoding a member of the ABCA transporter family, ABCA12, have been linked to harlequin ichthyosis, but the molecular function of the protein is unknown. To investigate the activity of ABCA12, we generated Abca12 null mice and analyzed the impact on skin function and lipid content.

Polymorphisms near EXOC4 and LRGUK on chromosome 7q32 are associated with Type 2 Diabetes and fasting glucose; the NHLBI Family Heart Study.

Background: The chromosome 7q32 region is linked to metabolic syndrome and obesity related traits in the Family Heart Study. As part of a fine mapping study of the region, we evaluated the relationship of polymorphisms to fasting glucose levels and Type 2 diabetes.

Methods: Thirty-nine HapMap defined tag SNPs in a 1.

Sepiapterin reductase expression is increased in Parkinson's disease brain tissue.

The PARK3 locus on chromosome 2p13 has shown linkage to both the development and age of onset of Parkinson's disease (PD). One candidate gene at this locus is sepiapterin reductase (SPR). Sepiapterin reductase catalyzes the final step in the biosynthetic pathway of tetrahydrobiopterin (BH(4)), an essential cofactor for aromatic amino acid hydrolases including tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis.