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This article discusses a pediatric case of KMT2A-rearranged B-lymphoblastic lymphoma, a rare type of non-Hodgkin lymphoma in children. The KMT2A gene rearrangements are commonly found in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), but are rarely described in lymphomas. The patient in this case had a mass on his back, which was surgically removed and diagnosed as B-lymphoblastic lymphoma. The presence of a KMT2A-rearrangement led to the decision to treat the patient with high-risk chemotherapy. The article emphasizes the need for further research to determine the best treatment approach for this type of lymphoma. [Extracted from the article]

Chimeric antigen receptor T‐cell (CAR‐T) therapy has demonstrated unprecedented success in the treatment of various hematologic malignancies including relapsed or refractory (R/R) B‐cell acute lymphoblastic leukemia (B‐ALL). Currently, there are two FDA‐approved CD19‐directed CAR‐T cell products for the treatment of adults with R/R B‐ALL. Despite high remission rates following CD19 CAR‐T cell therapy in R/R B‐ALL, remission durability remains limited in most adult patients, with relapse observed frequently in the absence of additional consolidation therapy. Furthermore, the burden of CAR‐T cell toxicity remains significant in adults with R/R B‐ALL and further limits the wide utilization of this effective therapy. In this review, we discuss patient and disease factors that are linked to CAR‐T cell therapy outcomes in R/R B‐ALL and strategies to optimize durability of response to reduce relapse and mitigate toxicity in the adult population. We additionally discuss future approaches being explored to maximize the benefit of CAR‐T in adults with B‐ALL. [ABSTRACT FROM AUTHOR]

Vector copy number (VCN), an average quantification of transgene copies unique to a chimeric antigen receptor (CAR) T-cell product, is a characteristic that must be reported prior to patient administration, as high VCN increases the risk of insertional mutagenesis. Historically, VCN assessment in CAR T-cell products has been performed via quantitative polymerase chain reaction (qPCR). qPCR is reliable along a broad range of concentrations, but quantification requires use of a standard curve and precision is limited. Digital PCR (dPCR) methods were developed for absolute quantification of target sequences by counting nucleic acid molecules encapsulated in discrete, volumetrically defined partitions. Advantages of dPCR compared with qPCR include simplicity, reproducibility, sensitivity and lack of dependency on a standard curve for definitive quantification. In the present study, the authors describe a dPCR assay developed for analysis of the novel bicistronic CD19 × CD22 CAR T-cell construct. The authors compared the performance of the dPCR assay with qPCR on both the QX200 droplet dPCR (ddPCR) system (Bio-Rad Laboratories, Inc, Hercules, CA, USA) and the QIAcuity nanoplate-based dPCR (ndPCR) system (QIAGEN Sciences, Inc, Germantown, MD, USA). The primer–probe assay was validated with qPCR, ndPCR and ddPCR using patient samples from pre-clinical CAR T-cell manufacturing production runs as well as Jurkat cell subclones, which stably express this bicistronic CAR construct. ddPCR confirmed the specificity of this assay to detect only the bicistronic CAR product. Additionally, the authors' assay gave accurate, precise and reproducible CAR T-cell VCN measurements across qPCR, ndPCR and ddPCR modalities. The authors demonstrate that dPCR strategies can be utilized for absolute quantification of CAR transgenes and VCN measurements, with improved test–retest reliability, and that specific assays can be developed for detection of unique constructs. [ABSTRACT FROM AUTHOR]

This study used content analysis of survey responses to help understand attitudes regarding taking risks across the adult lifespan. A sample of 842 U.S. adults ages 18-92 were asked to report their personal philosophy of taking risks, and what risks they felt people their age should take more often. Thematic categories were identified to classify the range of risk activities and explicit motives for taking risks. Responses were coded, and frequencies of those risk activities and motives were compared between young adults (ages 18-29), middle adults (30-59), and older adults (60+). Logistic regression was used to identify linear and curvilinear trends. Interpreting results within a lifespan developmental task framework, we concluded that risk taking may be valued as a way to create opportunities during young adulthood, a means to capitalize on those opportunities in middle adulthood, and as a strategy for managing resources and well-being in late adulthood. [ABSTRACT FROM AUTHOR]

Background Parents of overweight children frequently under-recognize their child's overweight status. We hypothesized that parents of preterm children would be more likely than parents of term children to incorrectly perceive their child's weight. Methods We recruited parents of term and preterm when children were 2 months to 2 years of age. Small for gestational age infants were excluded. We compared parents' perceived weight category with child's actual weight category, based on normative data (underweight, normal weight, or overweight). We based analyses on encounters and adjusted for within-child clustering across repeated measures. Results In the preterm (n = 94) and term (n = 1,263) cohorts, 12 and 13% of children, respectively, were overweight (weight-for-length ≥ 95th percentile). Among parents of overweight children, 91% in the preterm cohort and 90% in the term cohort reported their child as healthy weight. Among healthy weight children (weight-for-length 6th-94th percentile), parents in the preterm cohort were more likely to report their child as underweight compared with parents in the term cohort (24 vs. 7%; p < 0.001). Conclusion Parental perception of weight status was impaired among parents of overweight children regardless of gestational age. However, parents were more likely to perceive their healthy weight child as underweight if their child was preterm. [ABSTRACT FROM AUTHOR]

Reactive pleocytosis in the CSF has been observed with blinatumomab but has not been well-described. We performed a retrospective study of 88 patients who received intrathecal chemotherapy (IT) while on blinatumomab with CSF analyzed to determine if pleocytosis had an impact efficacy and safety. Blinatumomab was used for relapsed/refractory 62.5%, MRD-positive 31.8%, and consolidation in MRD-negative 5.7%. The incidence of pleocytosis in CSF was 51% and was more frequent after day 15 (55.8% vs. 18.2%, p = 0.025). Pleocytosis did not impact CR, clearance of MRD positivity, PFS and OS rates. Lower incidence of non-CNS extramedullary relapse was seen (3.7% vs. 30.8%, p = 0.011) with pleocytosis in CSF. Analysis of CSF by flow cytometry showed median CD4:CD8 ratio of 1.34. In conclusion, CSF pleocytosis is prevalent with blinatumomab but only demonstrated lower rates of non-CNS extramedullary relapse but no impact on CNS relapse or neurotoxicity. [ABSTRACT FROM AUTHOR]

Summary Pegaspargase is a key drug for the treatment of younger adults with acute lymphoblastic leukaemia (ALL). Pegaspargase‐associated hepatotoxicity is most common during induction, and its incidence increases with age and body mass index (BMI). We hypothesized that the delayed administration of pegaspargase during induction is associated with lower risk of hepatotoxicity while retaining efficacy. We retrospectively reviewed 141 adult patients with newly diagnosed ALL who received pegaspargase during induction from November 2013 to February 2024. There were 78 (55.3%) patients who received early pegaspargase (EP) on day 4 and 63 (44.7%) patients who received delayed pegaspargase (DP) on day 15. High‐grade hepatotoxicity (grade ≥ 3 transaminitis and/or hyperbilirubinaemia) occurred more frequently in the EP group (p = 0.06). Rates of complete remission and negative minimal residual disease post induction were not different between cohorts. Univariate logistic regression analysis showed that BMI and age significantly predicted an increased risk of high‐grade hepatotoxicity while DP was associated with a lower risk (odds ratio = 0.44; p = 0.04). Overall survival and event‐free survival were not significantly different between cohorts. Delaying pegaspargase administration from day 4 to day 15 during induction cycle in adults with ALL might reduce the risk of high‐grade hepatotoxicity without adversely impacting clinical efficacy outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the effects of antidepressants on the QT interval and the subsequent risk of cardiac arrhythmias. Topics mentioned include the differences between citalopram and escitalopram, a comparison of risk of QT interval prolongation with antidepressants, and risk factors for QT interval prolongation.

OBJECTIVE To compare the doses of propofol required to induce general anesthesia in dogs premedicated with acepromazine maleate or trazodone hydrochloride and compare the effects of these premedicants on cardiovascular variables in dogs anesthetized for orthopedic surgery. DESIGN Prospective, randomized study. ANIMALS 30 systemically healthy client-owned dogs. PROCEDURES 15 dogs received acepromazine (0.01 to 0.03 mg/kg [0.005 to 0.014 mg/lb], IM) 30 minutes before anesthetic induction and 15 received trazodone (5 mg/kg [2.27 mg/lb] for patients > 10 kg or 7 mg/kg [3.18 mg/lb] for patients < 10 kg, PO) 2 hours before induction. Both groups received morphine sulfate (I mg/kg [0.45 mg/lb], IM) 30 minutes before induction. Anesthesia was induced with propofol (4 to 6 mg/kg [1.82 to 2.73 mg/lb], IV, to effect) and maintained with isoflurane or sevoflurane in oxygen. Bupivacaine (0.5 mg/kg [0.227 mg/lb]) and morphine (0.1 mg/kg [0.045 mg/lb]) were administered epidurally. Dogs underwent tibial plateau leveling osteotomy (n = 22) or tibial tuberosity advancement (8) and were monitored throughout anesthesia. Propofol induction doses and cardiovascular variables (heart rate and systemic, mean, and diastolic arterial blood pressures) were compared between groups. RESULTS The mean dose of propofol required for anesthetic induction and all cardiovascular variables evaluated did not differ between groups. Intraoperative hypotension developed in 6 and 5 dogs of the acepromazine and trazodone groups, respectively; bradycardia requiring intervention developed in 3 dogs/group. One dog that received trazodone had priapism 24 hours later and was treated successfully. No other adverse effects were reported. CONCLUSIONS AND CLINICAL RELEVANCE At the described dosages, cardiovascular effects of trazodone were similar to those of acepromazine in healthy dogs undergoing anesthesia for orthopedic surgery. [ABSTRACT FROM AUTHOR]