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Obsessive-compulsive disorder (OCD) is an anxiety disorder with significant morbidity whose pathophysiology is not fully understood. Neuroimaging studies have characterized OCD in terms of elevated striatal and prefrontal reactivity to emotion provocation. This neural model may be informed by investigation of functional connectivity in OCD, identifying alterations in how sensory information is integrated into frontostriatal regions. The current study employed functional magnetic resonance imaging (fMRI) to compare neural activity and connectivity in 31 OCD patients (12 washing and 19 checking subtypes) and 17 healthy volunteers in an emotion provocation paradigm using visual stimuli. OCD status was associated with hyper-activation of the posterior cingulate (PCg) in response to emotion provocation. Additionally, OCD patients demonstrated elevated PCg functional connectivity with the visual cortices and frontostriatal regions. Exploratory analyses suggested that stimulus-provoked activity and connectivity was elevated for checking subtypes in motor cortices, and elevated in washing subtypes in the anterior insula and orbitofrontal cortex. The PCg's role in moderating connectivity between the visual cortex and frontolimbic regions is muted in OCD, consistent with the PCg's suggested role in regulating attention towards emotional stimuli. Exploratory analyses suggest distinct PCg connectivity profiles in OCD subtypes, with checking linked to motor activation, but washing linked to a network supporting emotional salience. The study was not powered to fully investigate the effects of medication, patients often endorsed secondary symptom subtypes that muddied washing/checking distinctions, and the emotion provocation paradigm was of limited intensity compared to life stressors.

Chimeric antigen receptor (CAR) T‐cell is the most recent version in the evolution of cellular therapy with promising responses, which has revolutionized the management of some hematological malignancies in the current times. As the clinical use has progressed rather rapidly since the first approval in 2017, toxicities beyond cytokine release syndrome and immune effector cell‐associated neurological syndrome have surfaced. Cytopenias are common in <30 days (“early”), 30–90 days (“short‐term”) as well as >90 days (“prolonged”); and have clinical implications to patient care as well as resource utilization. We review the details of etiology, factors associated with cytopenias, and management considerations for patients with cytopenias for each of these time‐frames. This would potentially serve as a clinical guide for hematological toxicity or CAR‐T‐OPENIA, which is commonly encountered with the use of CAR T‐cell therapy.

The advent of novel immunotherapies, such as blinatumomab, inotuzumab, and chimeric antigen receptor (CAR) T cell therapy, has revolutionized the therapeutic landscape in the treatment of relapsed/refractory B cell acute lymphoblastic leukemia, but can be associated with specific toxicities. We review unique toxicities of each of these in this article. Blinatumomab, a bispecific T cell engager, has been associated with cytokine release syndrome (CRS) and neurological toxicities, both of which can be prevented and managed with corticosteroids. Inotuzumab is a calicheamicin-conjugated CD22 targeting antibody. The calicheamicin component of the drug is likely associated with the hepatotoxicity seen with inotuzumab, especially sinusoidal obstruction syndrome, which can happen both in the context of the drug alone, and also with allogeneic stem cell transplantation. QT prolongation has also been noted with inotuzumab. CAR T therapy uses genetically modified autologous T cells directed against CD19, a known target on B cells. CRS and neurological symptoms, formally termed as immune-effector-cell-associated neurological syndrome, have been described along with hypogammaglobulinemia, cytopenias, and infections.

The aim of this study is to compare clinical outcomes of patients who underwent allogeneic stem cell transplantation (HCT) for myelofibrosis with reduced intensity conditioning (RIC) using either Busulfan Fludarabine (BuFlu), Fludarabine Bis-chlorethyl-nitroso-urea/ carmustine Melphalan (FBM) or Fludarabine Melphalan (FluMel) regimens. Sixty-one patients were identified who underwent HCT with one of these RIC regimens. Overall survival (OS) was not different in the 3 groups. However, 100% donor chimerism was seen in more frequently at day +30 and day +100 in patients who received FBM or FluMel than BuFlu, in both CD3 and CD33 fractions. For instance, 100% donor chimerism in CD33 fraction was present in 100% patients in FBM cohort, 90% in FluMel cohort while 44% in BuFlu cohort at day +100. Acute graft-versus host disease, grade 2–4 and grade 3–4, was not statistically different in the 3 groups (BuFlu 47 and 35%, FBM 68 and 27%, FluMel 68 and 46%; p = 0.31 and 0.45). Relapses and non-relapse mortality was also not statistically significantly different. Our study shows similar OS with these 3 RIC regimens in myelofibrosis; although donor chimerism at day +30 and day +100 was better in patients who received FBM and FluMel.

Multiple studies have questioned the benefit of neutropenic diets in decreasing infections in patients with cancer, but recent surveys showed that such diets are still prescribed. In this study, we sought to evaluate the effectiveness of neutropenic diet in decreasing infection and mortality in neutropenic patients with cancer with neutropenia. This review is an update of a previously published systematic review. We searched different databases to identify comparative studies that investigated the effect of neutropenic diet compared with regular diet in neutropenic adults and children with cancer. We conducted random-effects meta-analyses using the Der-Simonian and Laird method to pool treatment effects from included studies. Outcomes of interest were mortality, bacteremia/fungemia, major infections, quality of life, and the composite outcome for neutropenic fever and/or infection. We included six studies (five randomised) with 1116 patients, with 772 (69.1%) having underwent haematopoietic cell transplant. There was no statistically significant difference between neutropenic diet and regular diet in the rates of major infections (relative risk [RR] 1.16; 95% CI 0.94 to 1.42) or bacteremia/fungemia (RR 0.96; 95% CI 0.60 to 1.53). In haematopoietic cell transplant patients, neutropenic diet was associated with a slightly higher risk of infections (RR 1.25; 95% CI 1.02 to 1.54). No difference in mortality was seen between neutropenic diet and regular diet (RR 1.08, 95% CI 0.78 to 1.50). There is currently no evidence to support the use of neutropenic diet or other food restrictions in neutropenic patients with cancer. Patients and clinicians should continue to follow the safe food-handling guidelines as recommended by the U.S. Food and Drug Administration.

Myeloproliferative neoplasms (MPN) are chronic clonal disorders characterized by overproduction of myeloid-lineage blood cells and potential risk of evolution to acute myeloid leukemia (AML). Chronic myeloid leukemia (CML) is distinct from other MPNs in that its pathophysiology stems from the BCR-ABL fusion protein of the Philadelphia chromosome (Ph +). Though there are known cases of Ph- and Ph + MPNs coexisting in a single patient, overall prevalence has never been quantified in a prospective cohort. Here, we review our center’s MPN registry, which shows 0.6% of Ph- MPN patients later developed CML. This development occurred no less than 10 and up to 36 years after Ph- MPN diagnosis. This rate of chronic transformation exceeds what is expected, as the incidence of CML in the United States is 2 per 100,000 people-years. The probability of this CML case rate in an average-risk population is less than 0.001%, suggesting there are shared risk factors between Ph- and Ph + MPNs. We speculate that these risk factors may include exposures, genetic predispositions, or be inherent to disease biology. Abrupt-onset leukocytosis heralded post-MPN CML in all cases here and suggests this salient clinical feature should trigger hematologists to consider this diagnosis and perform appropriate testing.

Chimeric antigen receptor (CAR) T-cell therapy (CAR T therapy) is a treatment option for patients with relapsed or refractory multiple myeloma that has led to unprecedented treatment outcomes. Among CAR T therapies available, ciltacabtagene autoleucel (cilta-cel) is a good candidate for outpatient administration due to its generally predictable safety profile. There are multiple advantages of outpatient administration of cilta-cel, including reduced healthcare burden, expanded access, and patient autonomy. This mixed methods qualitative study aimed to identify key factors for outpatient administration of CAR T and best practice recommendations by combining a targeted literature review with expert interviews and panels. The targeted review (Phase 1) aimed to identify factors for outpatient CAR T administration in the US and determine key topics for the exploratory interviews (Phase 2) and expert panels (Phase 3), which aimed to inform on best practices and challenges of outpatient CAR T administration (focusing on cilta-cel). Participants in clinical and administrative positions based in treatment centers that had experience with real-world outpatient administration of cilta-cel were recruited. Seventeen studies were identified in Phase 1. Key factors for outpatient administration included the development of protocols for CAR T complications, education for caregivers, outpatient specialists, hospital staff, and emergency services staff for identification and referral after possible adverse events, the creation of multidisciplinary teams for effective communication and management, straightforward patient intake processes encompassing financial eligibility review and provision of patient education materials, and close patient monitoring throughout the treatment journey. In Phase 2, 5 participants from 2 centers were interviewed. In Phase 3, 14 participants across 6 treatment centers were interviewed. Two 90-minute virtual panel discussions took place. All participants agreed that cilta-cel can be safely and effectively administered in an outpatient setting. Key recommendations included the creation of educational resources for patients and caregivers, the development of standard operating procedures, dedicated outpatient infrastructure and establishment of interdisciplinary teams, outpatient monitoring for toxicity management, and monitoring of the reimbursement landscape. This study offers a comprehensive understanding of the feasibility of outpatient cilta-cel administration in participating CAR T centers and provides actionable recommendations while acknowledging existing challenges.

Human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus, is a DNA oncovirus known for its role in the development of Kaposi’s sarcoma (KS) and several lymphoproliferative disorders (LPDs). HHV-8 promotes lymphoproliferation via the activation of the interleukin-6 receptor signaling pathway, as well as a host of other regulatory mechanisms. The spectrum of HHV-8-associated LPDs is increasing. The World Health Organization has recently updated the classification of HHV-8-associated LPDs by introducing HHV-8-positive germinotropic LPD (GLPD) in addition to the previously recognized entities of HHV-8-positive diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), primary effusion lymphoma (PEL), and HHV-8-positive multicentric Castleman’s disease (MCD). We present here a case of an HIV-positive woman with a history of KS, who later developed three HHV-8-associated LPDs, including HHV-8-positive MCD, PEL, and GLPD. To the best of our knowledge, this is the first reported case of a patient with this combination of individually rare HHV-8-associated LPDs. This case illustrates the spectrum and the sequential development of the different clinical manifestations of HHV-8-associated diseases. Detection of HHV-8 can have clinical significance in the diagnosis and management of certain HHV-8-associated conditions. Recently discovered variants of HHV-8-associated LPDs indicate that this group represents a diverse spectrum of disorders, whose classification may require further refinement beyond the currently recognized entities.

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are clonal myeloid malignancies that are characterized by dysplasia resulting in cytopenias as well as proliferative features such as thrombocytosis or splenomegaly. Recent studies have better defined the genetics underlying this diverse group of disorders. Trisomy 8, monosomy 7, and loss of Y chromosome are the most common cytogenetic abnormalities seen. Chronic myelomonocytic leukemia (CMML) likely develops from early clones with TET2 mutations that drive granulomonocytic differentiation. Mutations in SRSF2 are common and those in the RAS‐MAPK pathway are typically implicated in disease with a proliferative phenotype. Several prognostic systems have incorporated genetic features, with ASXL1 most consistently demonstrating worse prognosis. Atypical chronic myeloid leukemia (aCML) is most known for granulocytosis with marked dysplasia and often harbors ASXL1 mutations, but SETBP1 and ETNK1 are more specific to this disease. MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN‐RS‐T) most commonly involves spliceosome mutations (namely SF3B1) and mutations in the JAK‐STAT pathway. Finally, MDS/MPN‐unclassifiable (MDS/MPN‐U) is least characterized but a significant fraction carries mutations in TP53. The remaining patients have clinical and/or genetic features similar to the other MDS/MPNs, suggesting there is room to better characterize this entity. Evolution from age‐related clonal hematopoiesis to MDS/MPN likely depends on the order of mutation acquisition and interactions between various biologic factors. Genetics will continue to play a critical role in our understanding of these illnesses and advancing patient care.