中国实验血液学杂志最新文献

Objective: To investigate the effect of endothelial activation and stress index (EASIX) on the prognosis of patients with angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and to compare the clinical characteristics of patients in the low EASIX and high EASIX groups.

Methods: The clinical data of 59 newly diagnosed AITL and PTCL-NOS patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to September 2021 were retrospectively analyzed. The optimal cut-off value of EASIX was determined by receiver operating characteristic (ROC) curve; The chi-square test was used to analyze the correlation between EASIX and clinical features of patients with AITL and PTCL-NOS; The Kaplan-Meier survival curve was used to analyze the overall survival (OS) and progression-free survival (PFS) of the patients; Univariate and multivariate analyses were performed by using Cox proportional hazards model.

Results: The optimal cut-off value of EASIX was 0.95, based on which the patients were divided into a low EASIX (<0.95) group and a high EASIX (≥0.95) group. Compared with the low EASIX group, the high EASIX group had a higher proportion of patients with advanced Ann Arbor stage, higher risk according to IPI, elevated LDH, hypoproteinemia, anemia, B symptoms,extranodal involvement, and bone marrow involvement. Survival analysis showed that the OS and PFS of patients in the high EASIX group were significantly shorter than those in the lower EASIX group(P <0.001). The multivariate analysis showed that EASIX was an independent risk factor for OS ［HR=7.217 (95%CI : 1.959-26.587), P =0.003］ and PFS ［HR=2.718(95%CI : 1.032-7.161), P =0.043］ of PTCL patients.

Conclusion: High EASIX in newly diagnosed patients with AITL and PTCL-NOS suggests a poor prognosis, and high EASIX is a risk factor affecting prognosis of the patients.

Objective: To analyze the effect of peripheral blood hematopoietic stem cells (PBSC) collection from unrelated donors and its influencing factors.

Methods: A retrospective analysis was conducted on the mobilization and collection of PBSC from 113 unrelated donors at Yueyang Central Hospital from January 2021 to December 2023.

Results: 113 donors were successfully mobilized. The average count of PBSC mononuclear cells (MNC) and CD34⁺ cells were (12.40±7.41)×10⁸/kg and (10.64±8.07)×10⁶/kg, respectively. Univariate analysis showed that the PBSC CD34⁺ cells ratio of male donors was significantly higher than that in female donors (P =0.015). The peripheral blood (PB) white blood cell (WBC) count before collection was positively correlated with the PBSC nucleated cells count (r =0.388), and the donor's body weight, the PB CD34⁺ cell ratio before collection were positively correlated with the PBSC CD34⁺ cell ratio (r =0.259, r =0.780). The daily dose of rhG-CSF was negatively correlated with the PBSC CD34⁺ cell ratio (r =-0.285). Both rhG-CSF agents achieved successful mobilization. Multivariate analysis showed that PB WBC count before collection was a factor affecting the count of PBSC nucleated cells (P <0.001), while the PB CD34⁺cell ratio before collection was a factor affecting the PBSC CD34⁺ cell ratio (P <0.001).

Conclusion: The mobilization and collection of PBSC from unrelated donors are good, and the PB WBC count and CD34⁺ cell ratio before collection are reliable indicators for predicting the collection effect.

Objective: To analyze the effects of highdose methotrexate (HD-MTX) and lenalidomide as central nervous system (CNS) prophylaxis strategies in patients with diffuse large B-cell lymphoma (DLBCL).

Methods: The data of DLBCL patients with high risk of CNS recurrence who were initially treated in Fujian Provincial Hospital and Fujian Cancer Hospital from January 2012 to June 2022 were analyzed retrospectively. The patients were divided into HD-MTX group and lenalidomide group according to different prophylaxis strategies. Each group was further divided into high-risk group and medium-risk group based on CNS-IPI score and/or testicular involvement. The CNS relapse-free survival (CRFS) rate, adverse effects, and the effects of different prophylaxis strategies on overall survival (OS) rate and progression-free survival (PFS) rate were evaluated in different groups and subgroups.

Results: There were 200 patients enrolled in this study, 80 cases in lenalidomide group and 120 cases in HD-MTX group. According to the delivery timing of prophylactic HD-MTX, the patients in HD-MTX group were further divided into two groups: 80 cases at the end of induction chemotherapy and 40 cases during chemotherapy interval. At a median follow-up of 48(14-133) months, the 4-year CRFS rate, 4-year PFS rate, and 4-year OS rate of the HD-MTX group was 93.6%, 57.2%, and 68.8%, respectively, while that of the lenalidomide group was 90.4%, 69.4% and 75.6%. There were no significant differences in 4-year CRFS rate, 4-year PFS rate, and 4-year OS rate between HD-MTX group and lenalidomide group (all P >0.05), but lenalidomide group showed a trend of improvement in PFS. Further subgroup analysis showed that there was no significant difference in 4-year CRFS rate between high-risk patients of the two groups (91.7% vs 83.4%, P >0.05), while 4-year PFS rate showed difference (49.5% vs 64.2%, P <0.05). A total of 248 cycles were collected for adverse reaction analysis in the HD-MTX group, and 25 cycles occurred neutropenia accompanied with infection (10.1%), while in lenalidomide group 240 cycles were collected in which 20 cycles occurred neutropenia accompanied with infection (8.3%). Both the two groups had no treatment-related deaths.

Conclusion: Compared with HD-MTX, lenalidomide combined with immunochemotherapy can prevent CNS relapse, at the same time, improve prognosis, which is a safe and well tolerated central prophylaxis strategy.

Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia, and T cell immune dysfunction plays an important role in the formation of ITP. As a thrombopoietin receptor agonist (TPO- RA), eltrombopag can not only directly stimulate megakaryocytes to produce platelets, but also play an immunomodulatory role by inducing regulatory T cell generation and reducing proinflammatory factors. As a second-line treatment drug for adult ITP, eltrombopag is increasingly widely used in clinical practice. This review summarized the latest research progress on the mechanism of action, efficacy, safety, and how to reduce the dosage of eltrombopag in ITP.

Objective: To investigate the effects of down-regulation of p21 activated kinase 1 (PAK1) on the proliferation, differentiation, and apoptosis of myeloproliferative neoplasm (MPN) cells (6133/MPL) with thrombopoietin receptor MPL mutation at codon 515 (MPLW515L) and survival of 6133/MPL mice.

Methods: Interference with the protein level of PAK1 in 6133/MPL cells was assessed using lentivirus-mediated shRNA transfection technology. CCK-8 assay was used to detect the effect of down-regulation of PAK1 on the proliferation viability of 6133/MPL cells, and colony-forming ability was measured by cell counting. Flow cytometry was used to detect the PAK1 kinase activity on the ability of polyploid DNA formation and cell apoptosis in 6133/MPL cells. The expression of cyclin D1, cyclin D3 and apoptosis-related protein Bax was detected by Western blot. The infiltration of tumor cells in spleen and bone marrow of 6133/MPL mice were detected by HE staining.

Results: Down-regulation of PAK1 inhibited the proliferation and reduced the ability of cell colony formation of 6133/MPL cells. After knocking down PAK1, the content of polyploid DNA in 6133/MPL cells increased from 31.8 to 57.5% and 48.0%, and the proportion of apoptosis increased approximately to 10.8%. Down-regulation of PAK1 led to a reduction of infiltration of tumor cells in liver and bone marrow of 6133/MPL mice, thereby prolonging survival time.

Conclusion: Down-regulation of PAK1 can significantly inhibit the growth of 6133/MPL cells, promote the formation of polyploid DNA, induce 6133/MPL cell apoptosis, and prolong the survival time of 6133/MPL mice.

Objective: RS4;11 cell line was used to establish BCL-2 inhibitor-resistant cell lines of B-cell acute lymphoblastic leukemia (B-ALL) and explore the possible mechanisms of drug resistance.

Methods: RS4;11 cell line was continuously induced and cultured by low and ascending concentrations of BCL-2 inhibitors navitoclax and venetoclax to construct navitoclax-resistant cell line RS4;11/Nav and venetoclax-resistant cell line RS4;11/Ven. The cell viability was detected by MTT assay, and the cell apoptosis was detected by flow cytometry. Differentially expressed genes (DEGs) between RS4;11 drug-resistant cell lines and parental cell line were detected by transcriptome sequencing technology (RNA-seq), and mRNA expression levels of DEGs between drug-resistant cell lines and parental cell line were detected by real-time PCR (RT-PCR). Western blot was used to detect the expression levels of BCL-2 family anti-apoptotic proteins in drug-resistant cell lines and parental cell line.

Results: The drug-resistant cell lines RS4;11/Nav and RS4;11/Ven were successfully established. The resistance index (RI) of RS4;11/Nav to navitoclax and RS4;11/Ven to venetoclax was 328.655±47.377 and 2 894.027±300.311, respectively. The results of cell apoptosis detection showed that compared with the drug-resistant cell lines, RS4;11 parental cell line were significantly inhibited by BCL-2 inhibitors, while the apoptosis rate of drug-resistant cell lines was not affected by the drugs. Western blot assay showed that the expression of anti-apoptotic proteins of BCL-2 family did not increase significantly in drug-resistant cell lines. RNA-seq, RT-PCR and Western blot assays showed that the expression of EP300 in drug-resistant cell lines was significantly higher than that in parental cell line (P <0.05).

Conclusion: Drug-resistant B-ALL cell lines could be successfully established by exposing RS4;11 cell line to the ascending concentration of BCL-2 inhibitors, and the drug resistance mechanism may be related to the overexpression of EP300.

Objective: To investigate the early predictive value of halving time (HT) of BCR-ABL^IS for deep molecular response (DMR) in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitor (TKI).

Methods: The continuous data of newly diagnosed CML patients with complete case data and first-line imatinib treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to June 2022 were retrospectively analyzed. Combined with the clinical characteristics of the patients and the efficacy analysis at each time point, a logistic regression model was used to explore the independent influencing factors of DMR, and combined HT of BCR-ABL^IS with BCR-ABL^IS level at 3 months to predict DMR of the patients.

Results: Univariate and multivariate analyses showed that HT and 3-month BCR-ABL^IS levels were independent influencing factors for MR4, MR4.5, and stable MR4.5 ( P < 0.05). ROC curve analysis determined that the best cut-off value of HT was 28 days. Compared with patients with HT>28 d, patients with HT≤28 d were more likely to obtain DMR at 2, 3, and 5 years, respectively (74.2% vs 27.3%, 71.2% vs 22.7%, and 63.6% vs 25.0%, all P < 0.001). The patients were divided into 4 groups according to BCR-ABL^IS levels at 3 months and HT. Kaplan-Meier analysis showed that the patients in the BCR-ABL^IS≤10% and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABL^IS≤10% and HT>28 d group (P < ＜0.05); Patients in the BCR-ABL^IS>10% and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABL^IS＞10% and HT>28 d group ( P < 0.05).

Conclusion: In addition to BCR-ABL^IS level, HT of BCR-ABL^IS can be used as another important predictor of treatment efficacy in CML patients. The combination of BCR-ABL^IS level and HT has a more accurate predictive value for long-term molecular response of CML patients after TKI treatment.

Objective: To investigate the molecular mechanism and distribution characteristics of RhD negative phenotypes in Han population of blood donors in Wuhu city.

Methods: A total of 210 RhD^- samples from August 2021 to August 2022 were screened by serological test and collected from Wuhu Central Blood Station for the voluntary blood donor population. Exons 1 and 10 of the RHD gene were amplificated by PCR to determine whether the samples had the RHD gene. Exons 1-10 of the RHD gene were amplificated by PCR and zygosity analysis were performed in 82 samples containing D gene, and Sanger sequencing was performed on 55 samples containing all RHD exons to determine the genotype.

Results: Among 210 RhD^- specimens, 128 cases (60.38%) had RHD gene deletion. 27 cases had partial exons of RHD, including 2 cases with RHD*DVI.3/RHD*01N.01, 24 cases with RHD*01N.04/RHD*01N.01, and 1 case with RHD-CE(2-10)/RHD*01N.01. 55 cases had retained all of 10 exons, including 4 cases with RHD*01/RHD*01N.01, 6 cases with RHD*15/RHD*01N.01, 1 case with RHD*01W.72/RHD*01N.01, 1 case with RHD*15/RHD*01EL.01, 39 cases with RHD*01EL.01/RHD*01N.01, and the remaining 4 cases were determined to have no RHD gene deletion by zygosity analysis and sequencing showed the presence of 1227G>A mutation loci.

Conclusion: There is polymorphism in the molecular mechanism of RhD^- D gene in Wuhu blood donor population, among which RHD*01EL.01 and RHD*15 are the main variants in this region. The results of this study provide a theoretical basis for RhD blood group identification and clinical blood transfusion in this region.

Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal disorders originating from hematopoietic stem cells, characterized by hemocytopenia and a high risk of transformation to acute myeloid leukemia (AML). The expected survival time of MDS patients varies widely, and accurate prognostic assessment is particularly important. Currently, patients with MDS are usually classified into a higher-risk group (HR-MDS) and a lower-risk group (LR-MDS) based on clinical prognostic scoring systems, but these scoring systems have certain limitations. Patients with LR-MDS account for 2/3 of MDS patients, with a lower risk of disease progression and a better prognosis, and their treatment mainly relies on erythropoiesis-stimulating agents, immunosuppressants and component transfusion. However, some LR-MDS patients still have poor prognosis, and the existing prognostic scoring systems cannot accurately evaluate their prognosis. In this review, the potential factors that may influence the prognosis of MDS patients beyond the existing assessment criteria were briefly summarized, with the aim of providing reference for the prognosis evaluation and treatment of LR-MDS patients.