Hematology最新文献

Objective: To analyze the efficacy of daratumumab-based regimen in newly diagnosed multiple myeloma(NDMM) patients with paraskeletal plasmacytomas (PPs).

Methods: The medical data of 28 NDMM patients with PPs were retrospectively analyzed. The daratumumab-based regimen was divided into group A, and the daratumumab-free regimen was divided into group B. The risk factors, efficacy, and overall survival (OS) were compared between the two groups.

Results: The results of univariate COX regression analysis showed that only the grouping and creatinine were statistically significant. The HR value of group A was 0.30(0.10-0.88, p = 0.029), which was a protective factor for patient survival, and the HR value of creatinine was 1.00(1.00-1.01, p = 0.026), which was a risk factor for patient survival. There was a statistically significant difference in efficacy between the two groups, P = 0.025 < 0.05. The results showed that the efficacy of group A was better. There was a statistically significant difference in OS between the two groups (54:27, P = 0.002).

Conclusions: The results indicated that the treatment regimens containing daratumumab could prolong the OS of patients, suggesting that for MM patients with extramedullary disease(EMD), daratumumab-based combination treatment regimens can be given priority.

Variant acute promyelocytic leukemia (vAPL) represents a certain type of APL case whose specific fusion proteins, which are relevant but atypical variants, may fail to be identified by polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) and requires identification through next-generation sequencing (NGS) or RNA sequencing (RNA-seq). These patients often show insensitivity to arsenic trioxide (ATO) or all trans-retinoic acid (ATRA) and therefore exhibit unclear prognosis. Venetoclax (VEN), an oral small-molecule B-cell lymphoma 2 (BCL-2) inhibitor, demonstrates effectiveness and safety as a cytoreduction therapy for pediatric APL and has shown some promising effect on relapsed or refractory APL. However, only a few cases have been reported on the treatment of vAPL with a single drug or multiple drugs combined with VEN. Therefore, this study reported the first vAPL case with the TFG-RARA fusion gene, who achieved complete remission (CR) with oral administration of VEN and ATRA, and remained CR till submission. Our study indicated that VEN may have a good therapeutic effect and contribute to a better prognosis of vAPL and warranted further application among APL patients.

Allogeneic bone marrow transplantation is a curative intervention for both neoplastic and non-malignant conditions. However, not all patients have an HLA-matched donor. Therefore, the development of an approach that expand the donor pool was of paramount relevance. The development of post-transplantation cyclophosphamide as graft versus host disease prophylaxis allows the safe use of haploidentical donors, solving the donor availability problem to the vast majority of patients in need. The present paper reviews the history of the development of haploidentical transplantation at Johns Hopkins University, from the bench to the bedside.

Objective: Acute myeloid leukemia (AML) stands out as a malignancy of the stem cell precursors of the myeloid lineage. Bone-marrow mesenchymal stem cell-derived exosomes (BMSC-exos) affect AML progression. We explored the effects and mechanism of BMSC-exos on AML cell proliferation and apoptosis.

Methods: Human AML cells (MOLM-16, MV-4-11) and normal human hematopoietic cells (GM12878) cultured in vitro were treated with exos extracted from BMSCs that transfected with microRNA (miR)-139-5p-mimics, ovβ-catenin, or miR-139-5p-inhibitor. BMSC morphology was observed by a microscopy, and its adipogenic and osteogenic differentiation abilities were assessed by oil red O staining and alizarin red S staining. BMSC-exos were extracted by ultracentrifugation, and their morphology was observed by a transmission electron microscopy. BMSC-exos were identified by nanoparticle tracking analysis and Western blot. The binding sites between miR-139-5p and β-catenin were predicted by TargetScan database, and then validated by dual-luciferase reporter assay. mRNA levels of miR-139-5p and β-catenin, cell proliferation, and apoptosis were evaluated by RT-qPCR, CCK-8, and flow cytometry. The expressions of CD63, CD81, TSG101, and GRP94 and the proteins of β-catenin, Bax, and Bcl-2 were determined by Western blot.

Results: miR-139-5p was poorly expressed in AML cell lines. miR-139-5p overexpression reduced AML cell viability/proliferation/Bcl-2 level, and raised apoptosis/Bax level. BMSC-exos repressed AML cell proliferation and promoted apoptosis via miR-139-5p. miR-139-5p targeted to inhibit β-catenin expression. Subsequently, up-regulated β-catenin partially counteracted the effects of miR-139-5p in BMSC-exos on AML cell proliferation and apoptosis.

Conclusion: BMSC-exos targeted to repress β-catenin expression by miR-139-5p, limited AML cell proliferation and facilitated apoptosis.

Purpose: The study aimed to access the impact of related factors on the long-term survival of patients with B-cell acute lymphoblastic leukemia (B-ALL) by analyzing clinical characteristics of B-ALL patients, and observed the significance of dynamic measurable residual disease (MRD) assessment for the prognosis and treatment selection of B-ALL patients, aiming to deepen the understanding of the disease and improve the survival prognosis of B-ALL patients.

Methods: The clinical characteristics of 65 patients with B-ALL were collected to calculate the median overall survival (OS) and median disease-free survival (PFS), and to evaluate the significance of survival analysis guided by dynamic MRD assessment.

Results: The survival analysis based on dynamic MRD assessment suggested that B-ALL patients who maintained MRD negative status during dynamic assessment after induction chemotherapy had better survival outcomes in the comparison of progression-free survival between subgroups, with statistically significant differences (P = 0.0002 (HR: 0.26, 95% CI: 0.13-0.51)). High-risk B-ALL patients who maintained negative MRD status during dynamic assessment after induction chemotherapy had longer median progression - free survival, and the survival difference between subgroups was statistically significant (P = 0.0016 (HR: 0.28, 95% CI: 0.09-0.48)).

Conclusion: Dynamic MRD assessment had significant clinical value: maintaining negative MRD status during dynamic assessment can improve the prognosis and survival of B-ALL patients; dynamic MRD assessment after induction chemotherapy can help guide subsequent treatment, which could provide reference for the advancement of future treatment strategies.

Background: Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified in multiple myeloma (MM); its influence on the homing behavior in MM cells is unclear. This study elucidates the impact and mechanism by which MALAT1 affects the homing behavior in MM cells.

Methods: Bone marrow was obtained from patients with MM. MALAT1 and C-X-C motif chemokine receptor 4 (CXCR4) expression in cluster of differentiation 138-purified (CD138) plasma cells were detected by qRT-PCR and Western blotting. MALAT1, CXCR4, and C-X-C motif chemokine ligand 12 (CXCL12) influences on MM cell viability, proliferation, and invasion was monitored by CCK-8, 5-Ethynyl-2'-deoxyuridine, and Transwell assays. qRT-PCR, Western blotting, and ELISA were utilized to detect homing effect-related proteins in MM cells, including intercellular adhesion molecule 1 (ICAM-1) and very late antigen-4 (VLA-4).

Results: MALAT1 and CXCR4 were overexpressed in CD138-purified plasma cells from bone marrow of MM patients, associating with bone damage. MALAT1 upregulated CXCR4 in MM cells. MALAT1 overexpression enhanced MM cell viability, proliferation, and invasion, whereas CXCR4 silencing reversed them. CXCR4 silencing attenuated MALAT1 induction on ICAM-1 and VLA-4 expression in MM cells. CXCL12 upregulation intensified MM cell proliferation and invasion and ICAM-1 and VLA-4 expression in MM cells. MALAT1 silencing counteracted the impact of CXCL12.

Conclusion: MALAT1 silencing may repress CXCL12 induction on MM cell proliferation, invasion, and homing behavior by inhibiting CXCR4. MALAT1 may be a promising target for MM treatment.

Objective: To summarize and analyze the clinical characteristics of the Hb Phnom Penh (HBA1:c.354_355insATC) variant in the Chinese population, and to guide clinical diagnosis and genetic counseling for hemoglobin disorders.

Methods: Peripheral blood samples were collected from patients, and hematological parameters, hemoglobin electrophoresis, and glycated hemoglobin chromatography were analyzed. PCR combined with reverse dot blot hybridization (RDB), nested PCR, gap polymerase chain reaction (Gap-PCR), Sanger sequencing, and third-generation sequencing (TGS) were performed to determine the gene variant.

Results: A total of 20 cases were examined, which included 11 neonates, 5 infants aged from 1 month to 6 months, and 4 adults. Hb Bart's band was measured in 14 infants. Thirteen infants (9 neonates and 4 infants of 1 month old) showed low levels of Hb Bart's bands (<1%), while one newborn exhibited a significantly elevated level of the Hb Bart's band (13.8%). Two adult patients were tested for glycated hemoglobin and had high levels at 7.0% and 7.2%, respectively, despite having normal blood glucose levels and no history of diabetes, indicating the presence of abnormal hemoglobin. Genetic testing confirmed that all 20 cases carried the HBA1:c.354_355insATC mutation, with one case being a compound mutation of - ^SEA/αα^{Phnom Penh}.

Conclusion: The HBA1:c.354_355insATC mutation leads to the production of abnormal hemoglobin (Hb Phnom Penh). Infants may exhibit low levels of Hb Bart's bands on hemoglobin electrophoresis, which have no salient pathological significance. The detection of abnormal HbA1c values suggests that this abnormal haemoglobin may be present.

Objectives: This study aimed to determine the prevalence of total blood cell abnormalities, hemoglobinopathies and G6PD deficiency and evaluate the efficacy of red blood cell (RBC) indices, mentzer index (MI) and naked-eye single tube red cell osmotic fragility (NESTROF) test as screening tools for diagnosis of β thalassemia trait among Yemeni blood donors.

Methods: A cross-sectional study was conducted with 106 volunteer blood donors who met the national standard criterion of blood donation. Various tests were performed, including complete blood count (CBC), serum ferritin, sickling test, G6PD assay, NESTROF test and high-performance liquid chromatography (HPLC).

Results: The prevalence of hematological abnormalities among blood donors reached 68.9%, with functional RBC abnormalities at 51.9%, leukopenia at 10.4%, thrombocytosis at 1.9%, and thrombocytopenia at 4.7%. Additionally, hemoglobinopathies were found in 21.7% of donors, with β-thalassemia trait at 3.8%, sickle cell trait at 1.9%, and suspected α-thalassemia trait at 16%, while G6PD deficiency and iron deficiency were present in 12.3% and 17.9% of donors, respectively. The NESTROF test, MCV and MCH demonstrated a sensitivity rate of 100%. MI and MCH exhibited the highest specificity followed by NESTROF test in the screening of β-thalassemia trait.

Conclusions: The prevalence of hemoglobinopathies and G6PD deficiency appear to be common among Yemeni blood donors. These results emphasize the necessity of comprehensive blood donation screening programs to safeguard the blood supply and promote early detection and management of hemoglobinopathies and G6PD deficiency in Yemen.

Objectives: Multiple myeloma (MM) is a class of malignant plasma cell diseases. An increasing application of autologous stem cell transplantation (ASCT) and anti-myeloma agents represented by proteasome inhibitors (PIs) has improved the response rates and survival of MM patients. Patients progressing within 12 months were recently categorized with functional high-risk (FHR), which could not be clarified by existing genetic risk factors, with poor outcomes. Our study aimed to investigate clinical indices related to FHR and seek prognostic roles in transplant-eligible MM patients.

Methods: Demographic and individual baseline clinical characteristics were compared by using the Pearson's chi-square and Mann-Whitney U test. Progression-free survival (PFS) and overall survival (OS) were described by Kaplan-Meier estimates and compared using the log-rank test. Logistic regression analysis was used to assess the association of baseline characteristics at MM diagnosis with FHR status.

Results: From 18th January 2010 to 1st December 2022, 216 patients were included and divided into two groups according to the FHR status. There was no difference in baseline data between the two groups. Renal impairment (RI, Scr > 2 mg/dL) was common in MM patients and made sense in FHR status. AST levels were validated as independent predictors for FHR status (p = 0.019).

Discussion: Patients with RI or higher AST levels (AST > 40 U/L) tended to have worse outcomes. However, transplants had apparently improved prognoses.

Conclusion: Therefore, in the PIs era, transplantations are still effective therapies for transplant-eligible MM patients.

Background: This study aims to investigate the correlation between NK and NKT cell proportion disparities and prognosis in patients with acute myeloid leukemia (AML).

Methods: Forty-four cases of acute myeloid leukemia patients were selected, and flow cytometry was utilized to evaluate the expression of bone marrow NK and NKT cells. Next-generation sequencing technology was employed to detect genetic mutations in these 44 AML patients, and the rates of first induction remission and overall survival were recorded. Comparisons were made to analyze the respective differences in NK and NKT cell proportions among AML patients with various genetic mutations and risk stratifications.

Results: The FLT-3-ITD+ group exhibited a significant increase in the proportion of NK cells compared to the normal control group and FLT3-ITD+/NPM1+ group, whereas the proportion of NKT cells was significantly decreased. Additionally, the CEBPA+ group showed an increased proportion of NKT cells compared to the TP53+ group and ASXL1+ group. The high-risk group had a higher proportion of NK cells than the intermediate-risk group, while the proportion of NKT cells was lower in the high-risk group compared to the intermediate-risk group.Patients achieving first induction remission displayed a higher proportion of NKT cells at initial diagnosis compared to those who did not achieve remission. The distribution of NK cells show significant differences among AML patients in different survival periods.

Conclusion: This results implies that distinct genetic mutations may play a role not only in tumor initiation but also in shaping the tumor microenvironment, consequently impacting prognosis.