[Rinsho ketsueki] The Japanese journal of clinical hematology最新文献

Hypokalemia is common in allogeneic hematopoietic stem cell transplantation (allo-HCT) patients and is associated with non-relapse mortality (NRM). Therefore, it is extremely important to replace potassium adequately. We evaluated the safety and efficacy of potassium replacement therapy by retrospectively analyzing the incidence and severity of hypokalemia in 75 patients who received allo-HCT at our institution. 75% of patients developed hypokalemia during the allo-HSCT, and 44% of patients had grade 3-4 levels of hypokalemia. NRM was significantly higher in patients with grade 3-4 hypokalemia than in patients without severe hypokalemia (one-year NRM: 30% vs 7%, p=0.008). Although 75% of the patients required potassium replacement that exceeded the range of potassium chloride solutions package inserts in Japan, we did not experience any adverse events associated with hyperkalemia. Our current observations suggested that the Japanese package insert for potassium solution injection should be revised for potassium needs.

Using the "periodic confirmation sheet" employed in the safety management procedure of thalidomide drugs, we looked at whether patients' knowledge of compliance with the procedure varies depending on the length of the gap between confirmations. In 31 centers, 215 participants were male patients and female patients who might be pregnant participants. Subjects have treated a group of patients who used periodic confirmation slips at the standard confirmation interval and a group of patients who increase the confirmation interval to 4 or 6 months, the % of respondents that correctly answered each of all six questions in questions 1-6 on the second comprehension questionnaire, excluding question 7 to confirm behavior change, was 87.0%. Comparing the percentage of correct answers to all questions the first time and the second time, no pregnancy cases were observed and there was no decline in the percentage of accurate responses after the second attempt for either group. One cannot judge changes in behavior. The mixed-effect model also additionally demonstrated non-inferiority in the patient group with the extended confirmation interval (a difference of -6.7% in the proportion of correct answers on the comprehension test (95%CI: -20.3-7.0%)), thus it appears that going forward, both male patients and female patients of potential pregnancy should complete the periodic confirmation form once every 4 or 6 months.

Lymphoblastic lymphoma (LBL) is a rare hematologic malignancy that originates from immature lymphocytes and usually expresses terminal deoxynucleotidyl transferase (TdT). Here, we report a case of TdT-negative B-LBL. A 71-year-old male patient presented to a hospital with shortness of breath. His chest computed tomography showed a mediastinal mass. Tumor cells did not express TdT but expressed MIC2, which led to LBL diagnosis. MIC2 is a useful marker for LBL diagnosis.

The clinical application of chimeric antigen receptor T-cell therapy (CAR-T therapy) has significantly altered the therapeutic strategy for B-cell tumors and is now being used to treat myeloid and solid tumors. Nonetheless, the efficacy of CAR-T cell therapy for myeloid and solid tumors has been limited, and several studies are being conducted to understand and overcome the underlying mechanisms. Recent research achievements have revealed that the properties of CAR-T cells, particularly their memory function, which can be continuously amplified in the body without exhaustion after administration, are closely related to CAR-T cell clinical efficacy. Furthermore, because the characteristics of CAR-T cells are greatly influenced by the quality of peripheral blood mononuclear cells, the raw material of CAR-T cells, and the T-cell used during the manufacturing process, attention has been drawn to the development of high-quality CAR-T cell manufacturing methods and combination therapies that maintain CAR-T cell memory function and suppress immune exhaustion. This article provides an overview of the current state of CAR-T cell development and clinical application to cancer, particularly emphasizing the development of manufacturing processes and efforts to improve CAR-T cell efficacy in combination therapy with molecular-targeting drugs.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved survival for patients with hematological malignancy, especially for those highly at risk of relapse. However, disease relapse after allo-HSCT remains the most common cause of treatment failure and death, even with conventional chemotherapy and donor lymphocyte infusion. Disease relapse in allo-HSCT can be reduced via pre-emptive treatment based on measurable residual disease and maintenance therapy for patients at high risk of relapse as promising treatment strategies. Recently, the development of novel agents and cellular therapies with high antitumor activity and less toxicity, which can be used in the post-transplant setting, has increased their clinical applications in the therapeutic approach. This review examines the current landscape and future strategies for maintenance therapy, mainly for AML and ALL after allo-HSCT.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has many subtypes with diverse clinical and biological features and outcomes. Next generation sequencing has revealed several novel subtypes, including the ZNF384 and MEF2D rearrangements. The clinical characteristics and outcomes of the largest series of BCP-ALL cases with ZNF384 and MEF2D rearrangements in an international collaborative study are described here. Patients with ZNF384 rearrangements appear to express various leukemic phenotypes, including BCP-ALL (with or without abnormal expression of myeloid markers) and B/myeloid mixed phenotype acute leukemia. We provide strong evidence that among BCP-ALL patients with a ZNF384 fusion, the partner gene is associated with demographic features and influences the outcome; particularly the EP300-ZNF384 fusion is associated with a low risk of relapse. MEF2D rearrangements have been primarily described in children and young adults with BCP-ALL. Previous research has suggested that patients with MEF2D-BCL9 fusion have a high risk of relapse. Despite having the MEF2D-HNRNPUL1 fusion gene, the prognosis was favorable. Improved diagnostic genomic testing will enable future prospective studies to clarify the clinical significance of the ZNF384 and MEF2D rearrangements in childhood and young adult BCP-ALL.

Fanconi anemia (FA), a hereditary bone marrow failure syndrome, has been suggested to be caused by a defect in DNA repair that removes endogenous DNA damage due to aldehydes. In seven Japanese children with aplastic anemia who clinically resembled FA, we identified biallelic variants of the ADH5 gene, encoding formaldehyde degrading enzyme, and a heterozygous ALDH2 variant (rs671). We conclude that the combined defects in ADH5/ALDH2 caused a new disorder now termed Aldehyde Degradation Deficiency Syndrome (ADDS). We suggest that this disease is caused by defective removal of formaldehyde produced by histone demethylation during hematopoietic cell differentiation. Therapeutic targeting of formaldehyde may reduce the hematopoietic deficits of FA as well as ADDS.