Hematology最新文献

Purpose: To explore the value of [¹⁸F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in assessing bone marrow involvement (BMI) and prognosis in newly diagnosed peripheral T-cell lymphomas (PTCLs) before treatment.

Methods: This retrospective study included 201 eligible PTCLs who received pre-bone marrow biopsy (BMB) and PET/CT. The status of bone marrow (BM) by PET was assessed using a visual examination and a quantitative index (the maximal standardized uptake value [SUV_max] of BM divided by the SUV_max of the liver [M/L]).

Results: Totally 148 patients had no evidence of BMI by PET or BMB; BMI was detected by both methods in 16 patients. The sensitivity and specificity of PET/CT for patients with confirmed BMI by BMB were 43.2% and 90.2%, respectively (κ =  0.353). In addition, 25 patients assessed by PET/CT staging (having stage I to II disease) had no evidence of BMI detected by both PET/CT and BMB. Image-guided biopsy was also recommended when PET/CT showed a focal FDG uptake outside the iliac crest. Survival analysis revealed that BMB was significant for overall survival (OS) (P = 0.020) while M/L for both progression free survival (P = 0.002) and OS (P < 0.001). In multivariate analysis, M/L (HR 1.825, 95% CI 1.071-3.110, P = 0.027) was an independent prognostic factor for OS. There were no statistical differences at the genetic level about BMI confirmed by PET or BMB.

Conclusion: PET/CT has a complementary role in assessing BMI and an ability to predict prognosis in PTCL patients.

While 1q21+ was common genetic alteration and found to have adverse effect on prognosis, the underlying genes remain unclear. Identification of related genes may provide additional help for rational intervention. The microarray dataset GSE2658 associated with MM was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were obtained, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate their functions. The hub genes were derived from the combined results of up-regulated DEGs and weighted gene coexpression network analysis (WGCNA). The receiver operating characteristic (ROC) curves of hub genes were plotted to evaluate correlation with 1q21+. Survival analysis and drug-gene interaction of hub genes were performed separately to find the prognostic value and potential targeted drugs. A total of 55 DEGs were identified. GO and KEGG pathway analyses suggested that the DEGs were related to several pathways of cell proliferation. NVL, IL6R, DUSP23 were proven to be highly correlated with 1q21+ and have adverse effects on prognosis. IL6R, DUSP23 were matched to known interaction-drug. This study revealed potential roles of hub genes in the pathogenesis and progression of MM with 1q21+, further investigations are needed to elucidate the mechanisms.

The development of effective prophylaxis strategies against graft-versus-host disease (GVHD) has contributed to the widespread use of haploidentical related hematopoietic cell transplantation (Haplo-HCT). Currently, GVHD prophylaxis containing posttransplant cyclophosphamide (PTCY) is considered the standard of care in Haplo-HCT, and recent studies have shown comparable results for PTCY-based Haplo-HCT and HCT from other donor sources. The conditioning regimen plays an important role in eradicating tumor cells to prevent disease relapse and suppressing the recipient's immune system to facilitate engraftment. PTCY-based Haplo-HCT was initially developed using a nonmyeloablative conditioning regimen consisting of fludarabine, cyclophosphamide and low-dose total body irradiation, but high relapse rates reinforced the need to intensify the conditioning regimen. In this respect, various myeloablative and reduced-intensity conditioning regimens have been investigated. However, the optimal conditioning regimens for PTCY-based Haplo-HCT have not yet been established, and this issue needs to be addressed based on data from patients undergoing the procedure. In this article, we review the existing literature on conditioning regimens for PTCY-based Haplo-HCT and discuss future perspectives.

Background: Relapsed/refractory acute lymphoblastic leukemia (R/R ALL) continues to be a major cause of mortality in children worldwide, with around 15% of ALL patients experiencing relapse and approximately 10% eventually dying from the disease. Early identification of R/R ALL in children has posed a longstanding clinical challenge.

Method: Genetic analysis of survival outcomes in pediatric patients with ALL from the TARGET-ALL dataset revealed five risk score factors identified through the intersection of differential genes (relapse/non-relapse) from the GSE17703 and GSE6092 databases. A risk score equation was formulated using these factors and validated against prognostic data from 46 ALL cases at our institution. Patients from multiple datasets were stratified into high and low-score groups based on this equation. Protein-protein interaction networks (PPI) were then constructed using the intersecting differential genes from all three datasets to identify hub nodes and predict interacting transcription factors. Additionally, genes related to cell pyroptosis with varying expression across these datasets were screened, and a multifactorial ROC curve (incorporating risk score and differential expression of pyroptosis-related genes) was generated. Furthermore, relationships among variables in the predictive model were depicted using a nomogram, and model efficacy was assessed through decision curve analysis (DCA).

Results: By analyzing the TARGET-ALL, GSE17703, and GSE6092 databases, we developed a prognostic risk assessment model for pediatric ALL incorporating BAG2, EPHA4, FBXO9, SNX10, and WNK1. Validation of this model was conducted using data from 46 pediatric ALL cases obtained from our institution. Following the identification of 27 differentially expressed genes, we constructed a PPI and identified the top 10 hub genes (PTPRC, BTK, LCK, PRKCQ, CD3D, CD27, CD3G, BLNK, RASGRP1, VPREB1). Using this network, we predicted the top 5 transcription factors (HOXB4, MYC, SOX2, E2F1, NANOG). ROC and DCA were conducted on pyroptosis-related genes exhibiting differential expression and risk scores. Subsequently, a nomogram was generated, demonstrating the effectiveness of the risk score in predicting prognosis for pediatric ALL patients.

Conclusions: We have developed a risk prediction model for pediatric R/R ALL utilizing the genes BAG2, EPHA4, FBXO9, SNX10, and WNK1. This model provides a scientific foundation for early identification of R/R ALL in children.

Objectives: The main objective was to investigate the incidence of transfusion-associated graft-versus-host disease (TA-GVHD) in patients who underwent haploidentical hematopoietic cell transplants (HCT) and received non-irradiated leukoreduced blood components. The secondary objective was to describe our leukodepletion results in blood products obtained by the filters employed at our center.

Study design and methods: Clinical records from 2018 to 2023 were retrospectively analyzed, along with a prospective evaluation of residual leukocytes in blood components from June to November 2023 in order to confirm effectivity of our leukodepletion method.

Results: 150 patients were included, no cases of TA-GVHD were reported after using non-irradiated blood products. The incidence of grade 3-4 acute and moderate-severe chronic GVHD was 12.7% (n = 19) and 2.7% (n = 4), respectively. The cumulative incidence of death was 39.3% (n = 52) with a 3.7-year overall survival (CI 95%, 3.3- 4.1 years). Leukodepletion analysis showed a reduction of 99.93% in platelet concentrates and 99.98% in packed red blood cells.

Discussion: TA-GVHD in HCT remains a concern traditionally mitigated using blood product irradiation. Recent evidence obtained in favor of leukoreduction techniques question this need, especially in resource-limited settings.

Conclusion: These findings support leukoreduction as a primary TA-GVHD preventive measure,along with the advantage in cost reduction.

Background: Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI.

Methods: We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs).

Results: A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time.

Conclusions: Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.

Objective: The drug resistance of multiple myeloma (MM) cells is one of the main causes of relapse, refractory and progression of MM.

Methods: First, Western blot analysis was used to detect the expression levels of NLRP3, ASC, pro-IL-1β and cleaved IL-1β, and RT-qPCR was used to detect the mRNA expression levels of them. The expression levels of IL-1β and IL-18 in the supernatant were detected by ELISA, and the expression levels of these factors in the activated group and the control group were compared to verify the activation of BMMCs and KM3.

Result: 1. The protein expression of NLRP3 and cleavd-IL-1β in the BMMCs cells was significantly higher than that of the control group (P < 0.05). The mRNA expression levels of caspase-1 and IL-1β were higher than those of the control group (P = 0.03, P = 0.02). 2. The protein expression levels of NLRP3 and cleaved-IL-1β in the KM3 cells were significantly higher than those of the control group (P < 0.05). The expressions of caspase-1 mRNA(P = 0.016) and IL-1β mRNA(P = 0.037) were significantly increased compared with the control group. 3. The early apoptosis results of BMMCs showed that the apoptosis rate of the LPS+ATP+Dex group was lower than that of the Dex group (P = 0.017). The early apoptosis rate of the LPS+ATP+Dex+Vel group was decreased compared with the Dex+Vel group (P = 0.045). 4. The early apoptosis rate of KM3 in the LPS+ATP+Dex group was lower than that in the Dex group (P = 0.03).

Conclusion: 1. LPS+ATP can activate NLRP3 inflammasome in multiple myeloma cells. 2. Activation of NLRP3 inflammasome inhibits the early apoptosis of myeloma cells induced by dexamethasone and bortezomib.

Background: Imatinib (IM) is the primary treatment for patients with chronic-phase CML (CML-CP). However, an increasing number of CML-CP patients have developed resistance to IM. Our study aims to explore the expression of miR-629-5p in extracellular vesicles (EVs) from both IM-sensitive (K562) and resistant (K562-Re) CML cell lines and to investigate the impact of regulating miR-629-5p expression on the biological characteristics of K562 and K562-Re cells.

Methods: Assess miR-629-5p expression levels in IM-sensitive and resistant CML cell lines. Separate EVs and verify it. EVs from K562-Re cells were co-cultured with K562 cells to detect the expression level of miR-629-5p. Target genes of miR-629-5p were determined and validated through luciferase experiments. Examined by manipulating miR-629-5p expression in cells using transfection techniques. The expression level of phosphorylated proteins in the PI3K/AKT/mTOR signaling pathway after IM was detected in CML cell lines. In K562-Re cells, the expression level of phosphorylated protein in the PI3K/AKT/mTOR signaling pathway was detected after single transfection of miR-629-5p inhibitor and cotransfection of miR-629-5p inhibitor and siSENP2.

Results: Increasing concentrations of EVs from K562-Re cells elevated miR-629-5p expression levels. The expression levels of miR-629-5p in CML cells varied with IM concentration and influenced the biological characteristics of cells. SENP2 was identified as a target gene of miR-629-5p. Furthermore, miR-629-5p was found to modulate the SENP2/PI3K/AKT/mTOR pathway, impacting IM resistance in CML cells.

Conclusion: EVs from IM-resistant CML cells alter the expression of miR-629-5p in sensitive cells, activating the SENP2/PI3K/AKT/mTOR pathway and leading to IM resistance.

Objective: To analyze the hematological phenotype and genotype of HbA2: c.96-2A > G carriers.

Methods: The blood routine parameters and hemoglobin electrophoresis of rare cases were analyzed and identified by PCR combined with reverse dot blot (RBD-PCR), GAP-PCR and DNA sequencing.

Results: Among the 7 patients, one adult patient had normal hemoglobin levels, with slightly decreased mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Hb Bart's band was found in 6 neonates by hemoglobin electrophoresis, of which the content of Hb Bart's band in 1 neonate was 15.80%, and the content of Hb Bart's band in the other 5 neonates was 0.30%-0.90%. The results of genetic analysis showed that all the 7 patients had HbA2: c.96-2A > G (IVS-I-116A > G) mutation, in which 1 case was compounded with - ^SEA deletion.

Conclusion: HbA2: c.96-2A > G mutation carriers exhibit the phenotype of α-thalassemia, and when the HbA2:c.96-2A > G mutation is combined with - ^SEA deletion, an intermediate phenotype of anemia is produced.

Objectives: Acquired hemophilia A (AHA) is a rare autoimmune disorder that presents with spontaneous bleeding due to the development of autoantibodies against coagulation factor VIII. This study aims to highlight the challenges in diagnosing and treating AHA, particularly through presenting two cases managed with rituximab, an anti-CD20 antibody, to demonstrate its safety and efficacy as a treatment option.

Methods: Two male patients, aged 38 and 68, with significant bleeding episodes and prolonged activated partial thromboplastin time (aPTT), were evaluated. Both patients received standard care, including factor VIII replacement and corticosteroids. Due to persistent symptoms, rituximab was administered weekly for four weeks, and follow-up assessments were performed to monitor factor VIII levels, aPTT, and clinical symptoms.

Results: Both cases showed improvement with rituximab. In Case 1, a 38-year-old male with idiopathic AHA achieved normal factor VIII levels and aPTT, with complete resolution of symptoms and no recurrence. In Case 2, a 68-year-old male with congenital hemophilia A and superimposed AHA responded positively to rituximab, showing stabilized factor VIII levels and no further bleeding episodes at a six-month follow-up.

Discussion: The management of AHA is complex due to its rarity and severe bleeding risks. Although corticosteroids and bypassing agents are primary treatments, rituximab is emerging as a promising therapeutic option. Current literature supports rituximab for patients with contraindications to first-line agents or poor prognosis, yet further studies are required to assess its potential as a first-line treatment.

Conclusion: These cases emphasize the efficacy and safety of rituximab in managing AHA. Given its potential benefits, further randomized controlled trials are warranted to evaluate rituximab's role as a first-line treatment. A structured monitoring protocol is recommended to ensure safe administration and manage potential side effects associated with immunosuppressive therapy.