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The article focuses on a study regarding clinical risk classification of children having precursor of B cell acute lymphoblastic leukemia (B ALL) by using absolute lymphocyte count. Topics discussed include significantly high percentage of survival in children with ALL, division of patients in standard and high risk groups on the basis of white blood cell counts (WBC), incorporation of studies such as gene expression profiling, and improvement in sensitivity in risk stratification.

Background and Aims: Inhalation anesthesia suppresses the immune system and stimulates the growth of tumor cells, contrary to intravenous anesthesia. However, no consensus exists on which anesthetic technique is better for preventing cancer recurrence. Therefore, this study compared the effects of two different anesthetic techniques on natural killer cell cytotoxicity (NKCC) in hepatocellular carcinoma (HCC) patients undergoing open hepatic resection., Material and Methods: Patients diagnosed with nonmetastatic HCC were scheduled for hepatic resection and randomly assigned to receive either propofol- or desflurane-based anesthesia. The primary outcome was pre- and postoperative NKCC assay. Cytokine levels were assessed by measuring interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) levels, and the secondary outcome was postoperative cancer recurrence evaluated using diagnostic imaging scans for 2 years., Results: Twenty-eight patients were analyzed, including 15 and 13 in the total intravenous anesthesia (TIVA) and inhalation (INH) groups, respectively. Two patients in the INH group were excluded due to non-HCC postoperative pathologic results. At 24 h, the postoperative change in NKCC between both groups showed no significant differences at a ratio of effector cell: target cell = 1:1, 5:1, and 10:1 ( P = 0.345, 0.345, and 0.565, respectively). Also, there were no significant differences in IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ levels ( P = 0.588, 0.182, 0.730, 0.076, 0.518, 0.533, respectively). Postoperative tumor recurrence occurred in five and six patients in the TIVA and INH groups, respectively., Conclusion: NKCC did not differ significantly among HCC patients undergoing open hepatic resection under either propofol or desflurane anesthesia 24 h postoperatively., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Anaesthesiology Clinical Pharmacology.)

Background: A bidirectional promoter-driven chimeric antigen receptor (CAR) cassette provides the simultaneous expression of two CARs, which significantly enhances dual antigen-targeted CAR T-cell therapy., Methods: We developed a second-generation CAR directing CD19 and CD20 antigens, incorporating them in a head-to-head orientation from a bidirectional promoter using a single Sleeping Beauty transposon system. The efficacy of bidirectional promoter-driven dual CD19 and CD20 CAR T cells was determined in vitro against cell lines expressing either, or both, CD19 and CD20 antigens. In vivo antitumor activity was tested in Raji lymphoma-bearing immunodeficient NOD-scid IL2Rgamma null (NSG) mice., Results: Of all tested promoters, the bidirectional EF-1 α promoter optimally expressed transcripts from both sense (CD19-CAR) and antisense (GFP.CD20-CAR) directions. Superior cytotoxicity, cytokine production and antigen-specific activation were observed in vitro in the bidirectional EF-1 α promoter-driven CD19/CD20 CAR T cells. In contrast, a unidirectional construct driven by the EF-1 α promoter, but using self-cleaving peptide-linked CD19 and CD20 CARs, showed inferior expression and in vitro function. Treatment of mice bearing advanced Raji lymphomas with bidirectional EF-1 α promoter-driven CD19/CD20 CAR T cells effectively controlled tumor growth and extended the survival of mice compared with group treated with single antigen targeted CAR T cells., Conclusion: The use of bidirectional promoters in a single vector offers advantages of size and robust CAR expression with the potential to expand use in other forms of gene therapies like CAR T cells., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cytokine-induced killer (CIK) cells are a heterogeneous group of immune cells that exert potent MHC-unrestricted cytotoxicity toward various cancer cells in both solid and hematological malignancies., Objective: The purposes of this study were to compare the expansion and characteristics of cytokine-induced killer cells between a standard culture method and a gas-permeable culture method and to develop a clinical-scale expansion protocol for cytokine-induced killer cells using a gas-permeable culture method., Methods: We compared the absolute cell number, fold change, cell subsets, activation markers, cytokine concentrations, and cytotoxicity toward myeloid leukemia cell lines between cytokine-induced killer cells expanded using two different culture methods. Then, we determined the ability to achieve clinical-scale expansion of cytokine-induced killer cells using the gas-permeable culture method., Results: Cytokine-induced killer cells in the gas-permeable culture method group exhibited significantly better expansion but maintained similar cell subsets, activation markers, and cytotoxicity to those in the standard culture method group. In addition, we successfully manufactured cytokine-induced killer cells for clinical use using the gas-permeable culture method. We also showed the clinical efficacy of allogeneic cytokine-induced killer cells produced by the gas-permeable culture method in a patient with acute myeloid leukemia that relapsed after allogeneic hematopoietic stem cell transplantation. This patient maintained ongoing disease remission for 2 years with minimal side effects after cytokine-induced killer cell infusion., Conclusions: We successfully developed a simple and effective protocol for the ex vivo expansion of cytokine-induced killer cells using the gas-permeable culture method for clinical application.