2024  Vol. 8,  No. 1

column
Review
Abstract:
Hematopoietic diseases are characterized by the high heterogeneity of associated hematopoietic cells, which mainly affect the homeostasis of the hematopoietic system. Due to their potential for multilineage differentiation and expected immunomodulatory properties, mesenchymal stem cell (MSC) based therapies have demonstrated significant promise in treating hematologic diseases. They have been successfully applied in various conditions, including aplastic anemia, refractory/relapsed myeloid leukemia, immune thrombocytopenic purpura, etc. Therefore, the purpose of this article is to review the biological characteristics, clinical applications, and related mechanisms of MSCs in hematopoietic diseases.
Article
Abstract:

The current classification system for diffuse large B-cell lymphoma (DLBCL) cannot fully explain prognostic differences in DLBCL patients. Cuproptosis is a newly discovered programmed cell death which depends on copper ions. In this study, a prognostic model based on cuproptosis-related genes was constructed using a public database. COX regression analysis was performed on training set-GSE31312 to construct a prognostic model based on cuproptosis-related genes, and the validation set-GSE181063 was used to verify the prognostic model. Gene Set Enrichment Analysis (GSEA) was used to explore the underlying mechanism behind differences in the prognosis of DLBCL patients. Finally, molecular docking was used to screen out compounds that may act on cuproptosis-related genes. A prognostic model based on 5 cuproptosis-related genes was constructed (CDKN2A×1.547905713-DLAT×2.241073725-DLD×1.907442964-LIPT1×2.689158994-MTF1×2.069682266) from training set-GSE31312. According to this model, DLBCL patients were divided into high-risk and low-risk groups. The survival time of high-risk patients was significantly shorter than that of the low-risk group (p = 2.636 × 10−7). In the validation set-GSE181063, the survival time of the high-risk group was also shorter than that of the low-risk group (p = 2.462 × 10−3). Among the 5 cuproptosis-related genes, only CDKN2A played a tumorigenesis role. Finally, three small molecule compounds with the lowest CDKN2A binding energy were found by virtual docking: irinotecan, lumacaftor and nilotinib, which may be used as potential targeted drugs. A prognostic model based on 5 cuproptosis-related genes was constructed in this study, and 3 potential targeted inhibitors of CDKN2A were screened out by molecular docking.

Abstract:
This study aims to create a platelet donor database with detailed HLA epitope typing in the Jining area and to serve as a solid foundation for treating refractory thrombocytopenia patients who require platelet transfusions. HLA-A, -B epitope phenotype data were collected from a total of 565 unrelated healthy populations in the Jining area. According to the data, a platelet donor database was created and established with known HLA epitope phenotypes. The database donors' HLA-A, -B epitopes were tested separately by sequence-specific primer (PCR-SSP). According to the distribution frequency of HLA-A, -B epitope phenotypes (n = 565), the following results were obtained: 73 HLA-A, -B phenotypes, including 55 with a frequency > 0.003. The sum of frequencies was 96.81%. With a database size of 565 donors, an approximate 84.20% patient HLA-A, -B cross-reactive group (CREG) match coverage was achieved. When it was necessary for identical ABO-type platelet transfusion, the corresponding database modifications were made according to the distribution frequency of the ABO blood group of the population.This study provides the concept for a platelet epitope matching database. It establishes a donor database of known platelet HLA epitopes in the Jining population, which lays a solid foundation for the safe treatment of platelet transfusion in this area.
Abstract:

This study aims to evaluate the application value of erythrocyte-magnetized technology in the detection of irregular antibodies. A total of 10 113 patients requiring blood transfusion were selected for the detection of irregular antibodies by microcolumn gel test and erythrocyte-magnetized technology simultaneously. The saline solution method and in-tube indirect antihuman globulin test were used as reference comparisons. Their ability to detect low titer antibodies was evaluated. A total of 72 antibody-positive samples were detected with a detection rate of 91.67% by microcolumn gel test and 84.72% by erythrocyte-magnetized technology. IgG antibody detection ability was consistent; however, IgM antibody detection ability was significantly lower. Both of them had considerably low titer antibody detection ability. This study suggests that erythrocyte-magnetized technology could serve as a valuable platform for irregular antibody analysis in clinic.

Case Report
Abstract:

This paper reports two patients with core-binding factor AML (CBF-AML) who experienced molecular recurrence following allogeneic hematopoietic stem cell transplantation (allo-HSCT). They were given preemptive treatment with camrelizumab, an inhibitor of programmed cell death protein 1 (PD-1). In case 1, a 45-year-old male AML patient with persistent CBFβ-MYH11 fusion transcripts received allo-HSCT after complete remission (CR). After transplantation, CBFβ-MYH11 fusion transcript remained persistently positive even after treatment with the hypomethylating agent decitabine. Camrelizumab was administered eight months post-transplantation. After 3 cycles administered at two-week intervals, the CBFβ-MYH11 transcripts became negative. Only mild liver insufficiency and telangiectasia were observed. In case 2, a 20-year-old male AML patient with the AML1-ETO fusion gene experienced molecular recurrence post allo-HSCT, even after treatment with decitabine. Camrelizumab was then administered 1 year after transplantation. After 2 cycles, AML1-ETO transcripts gradually became negative. However, severe immune-related liver injury occurred. Liver function eventually recovered with treatment. In conclusion, PD-1 inhibitors may be an effective strategy for CBF-AML patients with late stage molecular recurrence after allo-HSCT and should be explored further.

Abstract:

Two of the main toxicities linked with chimeric antigen receptor T (CAR-T) cell therapy are cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). It is believed that an inflammatory factor storm resulting in organ dysfunction is the fundamental pathophysiology, and this has a significant impact on the survival rate following CAR-T cell therapy. While steroids and other IL-6R antagonists like Tocilizumab are useful treatment approaches, not all patients benefit from them. Following CD19-targeted CAR-T cell infusion, a 3-year-old kid with relapsed refractory B-cell acute lymphoblastic leukemia (ALL) started to have CRS on Day 1. Despite receiving steroids and tocilizumab early on, his illness worsened and eventually led to multiple organ failure, particularly heart failure. After receiving mesenchymal stem cells (MSCs) as a rescue treatment on Days 17 and 20, the patient's clinical symptoms were stabilized by Day 25. Negative microscopic residual disease (MRD) was achieved with CAR-T therapy, and CAR expression was maintained in peripheral blood until Day 75. The case implies that MSC may be a useful treatment for multi-organ dysfunction that results from severe CRS and ICANS brought on by CAR-T cell therapy.

Abstract:

Autoimmune hemolytic anemia (AIHA) is a serious condition characterized by the severe hemolysis caused by increased levels of autoantibodies that specifically attack erythrocytes. Autoantibodies present difficulties in identifying alloantibodies, increasing the likelihood of hemolytic transfusion reactions (HTRs). In this report, we presented a rare and severe case of fatal HTRs caused by alloantibodies known as anti-S and anti-Wra in a female patient who had been suffering from hemolytic anemia for four decades. The patient's blood group type showed a significant inconsistency, later verified as AB CcDee by serologic tests. The antibody identification revealed unique patterns of anti-S and anti-Wra antibodies, with a noticeable disparity in agglutination intensity rated as 3+. Consequently, her erythrocytes were subjected to a freeze-thaw process, and the eluate showed robust pan-reactivity. The patient's MNS and Diego blood systems were analyzed using genetic sequencing, which confirmed the absence of the S or Wra antigen. However, the presence of a weakly positive S antigen in the serological result indicated the possibility of transfusion of leukocyte-poor red blood cells (LPRs) that carry the S antigen. As a result, the patient started receiving LPRs with the same phenotype, while avoiding S and Wra antigens. In addition, we evaluated the patient's state and discussed the appropriate blood transfusion protocol for AIHA in this case. Medical practitioners must possess expertise in identifying autoantibodies and alloantibodies in AIHA and devising a suitable blood transfusion plan.

Abstract:

Acute promyelocytic leukemia (APL) with CPSF6-RARG fusion gene is a rare leukemia. Patients with this fusion are resistant to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), as well as conventional chemotherapy with anthracycline plus cytosine arabinoside. Therefore, it is necessary to explore new protocols for these patients to improve remission and survival. In this case, a 21-year-old female with APL of CPSF6-RARG fusion gene was resistant to daunorubicin combined with cytarabine, ATRA, and ATO. Then the patient underwent a combination of homoharringtonine and pegylated liposomal doxorubicin chemotherapy (homoharringtonine 2 mg/day from day 1–7, Ara-C 15 mg/m2 every 12 hours from day 1–7, Peg-Dox 40 mg/m2 divided over 3 days from day 1–3 and rhG-CSF 300 μg/day from day 0–8). Following one month of treatment, the patient reached CR. And after another two cycles of the HADG protocol with medium-dose Ara-C treatment, the CPSF6-RARG turned negative. Then the patient successfully received stem cell transplantation. Currently, the patient has survived disease-free for more than 2 years. This study indicates that a combination of homoharringtonine and pegylated liposomal doxorubicin chemotherapy is a successful treatment plan for AML resembling APL with the CPSF6-RARG fusion gene. However, further validation in larger sample sizes is required.

Letter to Editor
Abstract:
Book and News
Abstract: