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There are inconsistencies in the reporting of CD19 antigen status following treatment with CD19-targeted therapies. A majority of evidence comes from studies reporting small sample sizes. In this review, we systematically summarize published studies that have reported rates of CD19-negative relapse after treatment with either blinatumomab or CD19-directed CAR T-cell therapy and report the rates of CD19-negative relapse when evaluated in a standardized way across trials. CD19-negative relapse appears to occur more commonly in relapses following CAR T-cell therapy compared with blinatumomab, whether proportions are calculated among all treated patients (8.7% vs 4.5%) or among patients who relapse (30% vs 22.5%). The median (range) duration of follow-up was 29.3 (17.4-50.8) and 20.4 (6.9-49.0) months for publications on blinatumomab (n = 10) and CAR T-cell therapies (n = 23), respectively. There is a need for standardized reporting of CD19 antigen status in the setting of relapse following novel immunotherapies to inform clinical practice. [ABSTRACT FROM AUTHOR]

Pegaspargase is a modified version of asparaginase with prolonged asparagine depletion. It appears to be safe in adults <40 years old, but has a unique spectrum of toxicities, the risks of which appear to increase with age. The primary objective of this study was to evaluate pegaspargase tolerability and toxicity as assessed by evaluation of incidence and severity of adverse events. Secondary objectives included characterization of the reasons underlying pegaspargase discontinuation, when applicable. Grade 3/4 asparaginase-related toxicities with ≥10% incidence included: hyperbilirubinemia, hyperglycemia, hypertriglyceridemia, hypoalbuminemia, hypofibrinogenemia, and transaminitis. 63% of patients (38 of 60) received all intended doses of pegaspargase, with the most common reasons for discontinuation noted as hypersensitivity (12%), hyperbilirubinemia/transaminitis (8%), and hematopoietic transplantation in complete remission (10%). This study suggests that while hepatotoxicity and other known adverse effects are common, with careful monitoring, pegaspargase can safely be administered to adults with ALL age ≥40 years old. [ABSTRACT FROM AUTHOR]

Over the past recent years, CD19-targeted chimeric antigen receptor T (CAR T) cell has transformed the treatment of relapsed/refractory (R/R) B lymphoid hematologic malignancy. CAR T cell therapy elicits an excellent anti-tumor effect and extends long-term disease-free remission in these difficult-to-treat patients. Notwithstanding, despite the impressive anti-tumor efficacy, some patients fail to attain clinical response or relapse after extended follow-up. The success of CAR T cell therapy involves complex interplays between host, tumor, and CAR T cell-associated arrays. Researchers have extensively explored potential predictive biomarkers for response to CAR T cell therapy. Ability to identify clinical and biological factors associated with improved response will help determine appropriate patients for CAR T cell treatment and enhance the clinical outcome of this novel therapeutic approach. [ABSTRACT FROM AUTHOR]

Dysfunctional regulation of brain dopamine (DA) functions has been found in patients with drug addiction and various neurological disorders that frequently accompany disturbance in sleep behavior. In this study, the roles of the dopaminergic nervous system on the regulation of daily locomotor activity rhythm were investigated in Drosophila melanogaster. Reduced synaptic DA release by expressing tetanus toxin gradually attenuated peak activity levels by altering activity patterns, particularly under constant darkness. Besides, flies with a mutant dopamine transporter fumin ( fmn), in which the synaptic DA levels were elevated, displayed increased activities in both daytime and nighttime, but did more so at nighttime, suggesting that DA function is involved in regulation of fruit fly's nocturnal locomotor activities. Furthermore, flies treated with bromocriptine, an agonist of Drosophila dopamine D2 receptor (dD2R), exhibited nocturnal locomotor hyperactivity in a dose-dependent manner and this effect was inhibited in dD2R knockdown flies. When mutant flies null for period ( per), timeless ( tim), dClock ( dClk), or cycle ( cyc) were treated with bromocriptine, only cycle-null flies ( cyc 01) did not show induced nocturnal hyperactivities, suggesting that cyc might play a role in bromocriptine-induced nocturnal hyperactivities. Elevation of experimental temperature also increased nocturnal activities at the expense of daytime activities. The heat-induced increase in nocturnal activities gradually returned to basal levels at continuously elevated temperature. Inhibition of DA synthesis did not suppress heat-induced early development of nocturnal hyperactivity but prevented gradual decrement of initially elevated nocturnal activities, suggesting that DA impinges on certain adaptive roles in response to changes in environmental temperature. These results overall suggest that controlling dopaminergic transmission is important for daily locomotor behavior and bromocriptine-induced nocturnal hyperactivity which is mediated through dD2R receptor and CYC functions. In parallel to these results, excessive activation of dopaminergic neurotransmission, the primary cause of schizophrenia, is associated with abnormally elevated nocturnal locomotor activities through D2-type receptor in Drosophila. The results suggest that fruit flies are an excellent model system to provide some answers to previously unexplainable observations regarding the compromised dopaminergic nervous system and the related therapeutic agents. (Author correspondence: ) [ABSTRACT FROM AUTHOR]

Despite several behavior-genetic studies that have suggested roles played by doublesex ( dsx ) in neural tissues, it has not been demonstrated that the products of this gene are actually present in the central nervous system (CNS). In this report, we describe the cellular, spatial, and temporal expression patterns of dsx gene products in the developing and adult CNS by applying RT-PCR and immunohistochemical procedures. dsx gene products were detected in the CNS of 3rd-instar larvae, pupae, and adults. DSX-immunoreactive signals were observed within the brain and in both the thoracic plus abdominal ganglia of the ventral nerve cord. Most, but not all, cells inferred to contain DSX proteins (by the results of genetic controls for antibody specificity) were further determined to be neurons (by coexpression of a protein that marks such CNS cell types). Temporally varying expression of DSX was most prominently observed in the rapidly metamorphosing early and mid-pupal stages, suggesting that this gene contributes to establishment of sexually dimorphic neuronal structures which subserve adult sexual behaviors. Elements of the spatial and temporal patterns of DSX immunoreactivity also imply that sexually dimorphic dsx expression in certain neuronal clusters within the adult CNS could participate in ongoing operations of the mature nervous system with respect to the courtship behaviors that are affected by dsx mutations. [ABSTRACT FROM AUTHOR]

AbstractHypomethylating agents (HMA) and venetoclax (VEN) are commonly used in patients with IDH-mutated (IDHm) acute myeloid leukemia (AML) ineligible for induction chemotherapy. While prior studies demonstrated high response and survival rates with HMA/VEN in IDHm AML, the impact of treatment modifications in real-world settings is unclear. We retrospectively reviewed 89 IDHm AML patients treated with HMA/VEN from January 2018 to June 2023. CR/CRi rates were 76% in newly diagnosed (ND) and 55% in relapsed/refractory (R/R) patients, and median overall survival was 29.2 months (ND) and 17.1 months (R/R), respectively. Treatment modifications were common. Early VEN reductions were associated with lower response rates but not worse survival. Prolonged cycles were not associated with worse response rates or survival. Significant neutropenia and ED visits or unplanned hospitalizations were considerable before and after CR/CRi, though febrile neutropenia decreased afterward. HMA/VEN is efficacious, with treatment modifications not affecting survival, though long-term toxicities are notable. [ABSTRACT FROM AUTHOR]

In this article the authors discuss the article "Hairy Cell Leukemia Treated Initially With Purine Analogs: A Retrospective Study of 107 Patients From the Spanish Cooperative Group on Chronic Lymphocytic Leukemia (GELLC)" by M. Lopez Rubio, C. Da Silva, J. Loscertales et al., within the issue. They are critical of implicating minimal residual disease in hairy cell leukemia and are supportive of conducting additional research on the elimination of minimal residual disease in leukemia patients.