中国实验血液学杂志最新文献

Objective: To clarify the specificity of patient blood type and blood type antibody through patient blood type serological tests and molecular biology results, and to search for matching blood for patients.

Methods: Blood type serological methods were used for the identification of red blood cell ABO, RhD, and p blood type. Salt water method, microcolumn gel method and IAT method were used for irregular antibody screening and antibody specificity identification. Forward and reverse sanger sequencing was used to amplify specifically the third exon (CDS sequence) of the A4GALT gene, identify the mutation site and genotype of the gene.

Results: The patient's serological blood type was positive for type B and D, indicating a p phenotype. At the same time, anti-Tj^a was detected in the serum, and further sequencing of the A4GALT gene exon was performed, the homozygous mutation with G>C occurred at base 559, and the genotype ISBT was named A4GALT*01N.10. Molecular biology verification confirmed it to be p blood group. Serological methods confirm that the patient's serum contains anti-Tj^a.

Conclusion: The joint identification of the rare blood type-p blood type by serological and molecular biological methods is of great significance for safe clinical blood transfusion.

Objective: To evaluate the efficacy and side effects of venetoclax combined with azacitidine chemotherapy in the treatment of previously untreated adult patients with acute myeloid leukemia(AML).

Methods: A retrospective analysis was performed on 48 untreated adult AML patients admitted to the Department of Hematology, Affiliated Hospital of Jinggangshan University from January 2020 to December 2022. Among them, 26 patients received venetoclax combined with azacitidine chemotherapy (observation group), and 22 patients received daunorubicin plus cytarabine chemotherapy (control group). The differences in complete response (CR) rate, objective response rate (ORR), progressionfree survival (PFS), overall survival(OS) and adverse reactions (AR) were compared between the two groups.

Results: There was no significant difference in age, sex ratio, absolute value of trilineage cell and proportion of bone marrow primordial cells between the two groups before treatment (all P >0.05). The CR rate and the ORR rate of the observation group was significantly higher than that of the control group (P < 0.05). After treatment, there were no significant difference in the adverse reactions such as myelosuppression, granulocytosis, secondary infection, mucosal damage, liver and kidney damage, cardiotoxicity and gastrointestinal toxicity between the two groups (P >0.05). The median PFS and the median OS of the observation group were significantly better than those of the control group (P < 0.05).

Conclusion: The remission rate of venetoclax combined with azacitidine was higher than that of conventional chemotherapy in previously untreated adult acute myeloid leukemia. Venetoclax combined with azacitidine chemotherapy could reduce hematologic related side reactions and prolong the remission period and survival of AML patients.

Objective: To investigate the effect of flow cytometric minimal residual disease (MRD) detection at different time points during AML chemotherapy on prognosis.

Methods: 130 adult primary AML patients diagnosed and standardized with chemotherapy from March 2018 to March 2022 were retrospectively analyzed, MRD was detected by flow cytometry, Kaplan-Meier curves was used for survival analysis and log-rank test was used for variance analysis, and univariate and multifactor influencing patient survival with COX proportional risk regression model analysis. Cumulative incidence rate (CIR) analysis with competing risk model and variance analysis using Fine-Gray.

Results: There were 81 CR1, 26 CR2, 14 PR, and 9 NR patients in 130 patients. OS of the CR1 group was higher than that in the CR2, PR,and NR groups. OS of the CR2 group was higher than that in the PR group, but there was no statistically difference compared to the NR group. There was no statistically difference in OS between the PR and NR groups. 107 patients in CR1 and CR2 were grouped according to MRD detected by flow cytometry, and after the first induction chemotherapy, for patients in the MRD^- and MRD⁺ groups, the 4-year expected RFS rates were 65.3% and 27.9% respectively, the 4-year expected OS rates were 58.7% and 41.4% respectively, and the 4-year expected CIR were 34.7% and 69.7% respectively, with statistically significant differences between 2 groups (χ²=6.639, P =0.010; χ²=6.131, P =0.013 and χ²=6.637， P =0.010). After the second chemotherapy, for patients in the MRD^- and MRD⁺ groups, the 4-year expected RFS rates were 50.8% and 37.9% respectively, the 4-year expected OS rates were 49.2% and 44.5% respectively, and the 4-year expected CIR were 49.2% and 59.5% respectively, with no statistically significant differences between 2 groups (χ²=1.475, P =0.225; χ²=2.432, P =0.119 and χ²=1.416， P =0.234). During consolidation therapy, for patients in the MRD ^- and MRD⁺ groups, the 4-year expected RFS rates were 51.9% and 29.6% respectively, the 4-year expected OS rates were 67.5% and 24.6% respectively, and the 4-year expected CIR were 48.1% and 70.4% respectively, with statistically significant differences between 2 groups (χ²=20.982, P < 0.001; χ²=17.794, P < 0.001 and χ²=19.879， P < 0.001). For patients with MRD^- at all three time points and positive at either time point, the 4-year expected RFS rates were 69.9% and 33.3% respectively, the 4-year expected OS rates were 59.1% and 44.7% respectively, and the 4-year expected CIR were 30.1% and 65.1% respectively, with statistically significant differences between 2 groups (χ²=7.367, P =0.007; χ²=6.042, P =

Objective: To analyze the clinical characteristics and occurrence of thrombotic/bleeding events of patients with myeloproliferative neoplasm (MPN), and explore the main influencing factors, and create a risk prediction.

Methods: The clinical data of 126 MPN patients with BCR-ABL fusion gene negative in the Department of Hematology of Gansu Provincial Hospital from January 2016 to September 2021 were collected, and their clinical characteristics, occurrence of thrombotic/bleeding events and main influencing factors were analyzed and summarized retrospectively. Then, a risk prediction model for thrombotic/bleeding events in MPN patients was constructed.

Results: Among 126 MPN patients, 50 patients (39.7%) had experienced thrombotic/bleeding events, including 44 patients (34.9%) with thrombotic events and 6 patients (4.8%) with bleeding events. Among thrombotic diseases, cerebral thrombosis was the most common (23/44, 52.3%), followed by 9 cases of limb artery thrombosis mainly characterized by finger and toe tip artery ischemia, occlusion and gangrene (9/44, 20.5%). Bleeding events included intracerebral hemorrhage and gastrointestinal hemorrhage. Univariate analysis showed that hypertension, hyperhomocysteinemia, white blood cell (WBC) ≥10×10⁹/L, hematocrit (HCT) ≥49%, platelet (PLT) ≥600×10⁹/L and JAK2V617F gene mutation were risk factors for thrombotic/bleeding events in MPN patients, while CALR gene mutation was a protective factor. Multivariate analysis showed that hypertension and PLT≥600×10⁹/L were independent risk factors for thrombotic/bleeding events in MPN patients. The goodness of fit of the constructed risk prediction model was 0.872, and the area under the ROC curve was 0.838. The model was validated with clinical data, the sensitivity, specificity and accuracy was 78.85%, 87.83% and 84.13%, respectively .

Conclusion: The risk of thrombotic/bleeding events in MPN patients with high WBC count, hypertension and hyperhomocysteinemia is higher. Controlling hypertension and hyperhomocysteinemia and reducing WBC and PLT counts are helpful to prevent thrombotic/bleeding events and improve the life quality of patients.

Objective: To explore the causes of platelet aggregation in version 6.4 Trima Accel automated blood collection system and the effect of 2 intervention measures.

Methods: The data on platelet aggregation (n=61) and non-aggregation (n=323) of 61 donors in 2020 were collected and the causes of aggregation were analyzed. Then the 72 donors with platelet aggregation in 2021 were randomized into intervention group A (increasing the anticoagulant-to-blood ratio) and intervention group B (wrapping the donor's arm with an electric blanket to keep warm and improve the blood flow speed). The collection time, average blood flow speed, number of machine alarms, anticoagulant usage, deaggregation and citrate reaction of the two groups were compared.

Results: Platelet aggregation was negatively correlated with the average blood flow speed (r =-0.394) and positively correlated with the collection time (r =0.458). The equations for predicting aggregation and non-aggregation were constructed based on Bayesian and Fisher discriminant analysis, and the predicted accuracy was 77.1%. The comparison of the effects of two intervention measures showed that the average blood flow speed in group B was higher than that in group A; the collection time, number of machine alarms, anticoagulant usage and proportion of citrate reaction in blood donors in group B were all lower than those in Group A, all these differences were significant (P < 0.05). In the entire cohort in 2021, 90.28% of the products were immediately deaggregated after collection, and 9.72% of the products were deaggregated within 4 hours. There was no statistically significant difference in deaggregation between the two intervention groups (P >0.05).

Conclusion: During apheresis platelet collection, the predictive equations for aggregation and non-aggregation can be used to predict the occurrence probability of aggregation, and the intervention can be made in advance. Both intervention measures are effective in reducing platelet aggregation, however, measure B has the advantages of improving the speed of blood collection, shortening the collection time, reducing the alarm frequency and the anticoagulant usage, and reducing the incidence of citrate reaction in blood donors.

Objective: To investigate the effect of pre-treatment plasma Epstein-Barr virus (EBV) DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH).

Methods: The clinical characteristics, survival rate, and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study. Patients were divided into three groups, including the EBV DNA-negative group(<5.0×10² copies/ml), lower EBV-DNA loads group(5.0×10²-8.51×10⁴ copies/ml), and higher EBV-DNA loads group(＞8.51×10⁴ copies/ml), according to pre-treatment plasma EBV-DNA copy number. Cox regression model was established for screening prognostic factors. Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index (C-index) and calibration curves were calculated to verify model predictive and discriminatory capacity.

Results: Among 171 adult sHLH patients, 84 patients were not infected with EBV (EBV DNA-negative group), and 87 with EBV (EBV DNA-positive group, 48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group). Consistent elevations in the levels of liver enzymes (ALT and AST), LDH, TG, β ₂-microglobulin and ferritin across the increasing of EBV-DNA load (all P <0.05), while the levels of fibrinogen decrease (P <0.001). The median follow-up time was 52 days (range 20-230 days), and 123 patients died. The overall survival (OS) rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group (median OS: 40 days vs 118 days, P <0.001). Higher EBV-DNA loads had worse OS (median OS: 24 days vs 45 days vs 118 days, P <0.0001 for trend) compared to lower EBV-DNA loads and EBV DNA-negative group. Multivariate Cox analysis revealed that higher EBV-DNA loads (P =0.005), fibrinogen≤1.5 g/L (P ＝0.012), ferritin (P ＝0.041), associated lymphoma (P ＝0.002), and anti-tumor based strategy (P ＝0.001) were independent prognostic factors for OS. The C-indexes of 30 day, 90 days, 365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability. Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women, ferritin＞5 000 μg/L, β₂-microglobulin＞7.4 mmol/L and regardless of age, etiologies, HScore points.

Conclusion: The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH. The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for eval

Objective: To investigate the expression level of small nucleolar RNA (snoRNA) SNORA63 in bone marrow of patients with acute leukemia (AL) and its significance in the clinical diagnosis, treatment and prognosis of AL patients.

Methods: Bone marrow samples of 53 newly diagnosed AL patients and 29 healthy subjects in the Affiliated Hospital of Guangdong Medical University from March 2018 to December 2021 were collected. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of SNORA63 in bone marrow mononuclear cells of the two groups. The median expression level of SNORA63 in AL patients was used as the boundary value to divide the patients into SNORA63 high and low expression groups, and the relationship between the expression level of SNORA63 and the clinical characteristics, clinical indicators and prognosis of AL patients was analyzed and discussed.

Results: The relative expression level of SNORA63 in AL patients was significantly lower than that in healthy control group [0.3018 (0.0244-1.2792) vs 1.0882 (0.2797-1.9889)] (P < 0.01). The expression level of SNORA63 in AL patients without remission after initial treatment was significantly lower than that in healthy controls and the patients who received complete remission (CR) (P < 0.01), while there was no statistical difference in the expression level of SNORA63 between AML and ALL groups (P >0.05). The abnormal low expression of SNORA63 was closely related to fever, hemorrage, poor prognosis, efficacy, platelets (PLT), lactate dehydrogenase (LDH), albumin (ALB), and molecular biological abnormalities of AL patients (P < 0.05), but not significantly correlated with sex, age, AL subtype, pallor, fatigue, extramedullary infiltration, white blood cell count (WBC), hemoglobin (HGB), C-reactive protein (CRP), procalcitonin (PCT), fibrinogen (FIB) or chromosome karyotype (P >0.05). Meanwhile, overall survival (OS) and event-free survival (EFS) of AL patients in SNORA63 high-expression group were significantly higher than those in SNORA63 low-expression group (P < 0.05). Univariate Cox regression analysis showed that SNORA63, molecular biological abnormalities, fever, PLT and LDH were the factors influencing OS and EFS in AL patients (P < 0.05). Multivariate Cox regression analysis indicated that fever, molecular biological abnormalities and LDH were independent factors associated with OS and EFS in AL patients (P < 0.05).

Conclusion: SNORA63 is significantly down-expressed in AL patients, which is a molecular marker of great clinical value for disease monitoring and prognosis evaluation in AL patients.

Objective: To investigate the clinical characteristics and prognosis of primary bone marrow lymphoma.

Methods: The clinical data of 6 patients with primary bone marrow lymphoma admitted to Gansu Provincial People's Hospital from February 2011 to March 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized.

Results: The median age of 6 patients was 61(52-74) years old. There were 2 males and 4 females. All patients had fever and abnormal blood routine examination. Physical examination and imaging examination showed no lymphadenopathy, no extranodal lesions in lung, gastrointestinal, liver and spleen, skin, etc. After strict exclusion of systemic lymphoma involvement in the bone marrow, the diagnosis was confirmed by bone marrow examination, 5 cases were primary myeloid diffuse large B-cell lymphoma and 1 case was primary myeloid peripheral T-cell lymphoma (NOS). 1 case abandoned treatment, 5 cases received CHOP-like or combined R regimen， including 1 case of autologous stem cell transplantation. 4 cases died and 2 case survived. The median OS was 5.5 (1-36) months.

Conclusion: The prognosis of primary marrow lymphoma is poor, and bone marrow-related examination is an important means of diagnosis. Diffuse large B-cell lymphoma is the most common histomorphologic and immune subtype, and autologous hematopoietic stem cell transplantation may improve the prognosis.

Objective: To investigate the anti- chronic myelogenous leukemia (CML) activity of Nur77-specific agonist Csn-B combined with imatinib by promoting Nur77 expression, and explore the potential role of its signaling pathway.

Methods: Firstly, CCK-8 and Transwell assay were used to detect the inhibitory effects of Csn-B, imatinib, and their combination on the proliferation and migration of K562 cells. Furthermore, the apoptosis rate of K562 cells treated with Csn-B, imatinib, and their combination was detected by flow cytometry. The expression levels of Nur77, Pim-1, Drp1, p-Drp1 S616, Bcl-2 and Bax in K562 cells were detected by Western blot. Finally, the expression levels of reactive oxygen species (ROS) in K562 cells treated with Csn-B, imatinib and their combination were detected by immunofluorescence assay.

Results: The level of Nur77 in CML patients decreased significantly compared with normal population in dataset of GSE43754 (P < 0.001). Csn-B combined with imatinib could significantly inhibit the proliferation and migration of K562 cells (both P < 0.001), and induce apoptosis (P < 0.001). Csn-B promoted Nur77 expression in K562 cells, and synergistically enhanced imatinib sensitivity when combined with imatinib. Csn-B combined with imatinib could significantly enhanced ROS levels in K562 cells and mitochondria compared with single-drug treatment (both P < 0.001).

Conclusion: Csn-B combined with imatinib can enhance ROS expression and induce apoptosis of K562 cells through Nur77/Pim-1/Drp1 pathway.

Objective: To establish a model to predict the overall survival (OS) rate of patients with diffuse large B-cell lymphoma (DLBCL) based on systemic inflammatory indicators, and study whether the new model combined with inflammatory related parameters is more effective than the conventional model using only clinical factors to predict the OS of patients with DLBCL.

Methods: The clinical data of 213 patients with DLBCL were analyzed retrospectively. Backward stepwise Cox regression analysis was used to screen independent prognostic factors related to OS, and a nomogram for predicting OS was constructed based on these factors. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to evaluate the fitting of the model, the consistency index (C-index), area under receiver operating characteristic (ROC) curve (AUC) and calibration curve were used to evaluate the prediction accuracy of nomogram, and decision curve analysis (DCA) and Kaplan Meier curve were used to evaluate the clinical practicability of nomogram.

Results: Multivariate analysis confirmed that age, ECOG PS score, serum lactate dehydrogenase (LDH) level, systemic immune inflammatory index (SII), and prognostic nutritional index (PNI) were used to construct the nomogram. The AIC and BIC of the nomogram were lower than the International Prognostic Index (IPI) and the National Comprehensive Cancer Network (NCCN)-IPI, indicating that the nomogram had better goodness of fit. The C-index and AUC of the nomogram were higher than IPI and NCCN-IPI, indicating that the prediction accuracy of the nomogram had been significantly improved, and the calibration curve showed that the prediction results were in good agreement with the actual survival results. DCA showed that the nomogram had better clinical net income. Kaplan Meier curve showed that patients could be well divided into low-risk, medium-risk and high-risk groups according to the nomogram score (P < 0.001).

Conclusion: The nomogram combined with inflammatory indicators can accurately predict the individual survival probability of DLBCL patients.