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Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. The outcome of relapsed/refractory FL patients after multi-therapy is poor. The 64th American Society of Hematology annual meeting in 2022 announced the latest updates on relapsed/refractory FL, including targeted therapy, bio-specific antibodies and chimeric antigen receptor T-cell. This review provides an overview of these updates.
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Follicular lymphoma (FL) is the most common indolent B-cell lymphoma. Although patients with FL generally have a good prognosis, the treatment of relapsed/refractory FL remains a challenge. The 63rd American Society of Hematology (ASH) Annual Meeting announced the latest updates on relapsed/refractory FL, including the usage of targeted therapy, bio-specific antibodies and chimeric antigen receptor T-cell (CAR-T) therapy. This article provides an overview of the updates in combination with the reports presented at the ASH Annual Meeting.
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Objective:To explore the effects of apatinib on the proliferation and apoptosis of FLT3-ITD mutant acute myeloid leukemia (AML) cells, and to explore the related mechanisms.Methods:The logarithmic growth phase FLT3-ITD mutant AML cell lines MV4-11 and MOLM-13 were treated with different concentration of apatinib for 48 hours. The cell proliferation was detected by CCK-8 method. Flow cytometry was performed to examine the effect of apatinib on apoptosis. The cell mitochondrial membrane potential changes were detected by JC-1. Then the expression changes of vascular endothelial growth factor receptor 2 (VEGFR2) pathway-related proteins were examined by Western blot.Results:Apatinib had proliferation inhibitory effects on both MV4-11 and MOLM-13 cells, and the half-maximal inhibitory concentration (IC 50) at 48 hours was (2.23±0.42) μmol/L and (4.08±2.62) μmol/L, respectively. After exposure to apatinib with increasing concentrations (10, 20, 30, and 40 μmol/L) for 48 h hours, the percentage of apoptotic cells was significantly increased in MV4-11 cells [(81.95±1.15)%, (88.80±0.23)%, (97.46±0.49)%, and (99.29±0.05)%] and MOLM13 cells [(47.30±0.87)%, (67.00±3.71)%, (82.60±2.89)%, and (98.06±5.34)%] in a dose-dependent manner, and the differences were statistically significant ( F = 6 915.0, P < 0.01; F = 5 385.0, P < 0.01). Detection of mitochondrial membrane potential by JC-1 method showed that after MV4-11 and MOLM-13 cells were treated by 10, 20, 30, and 40 μmol/L apatinib for 24 hours, the JC-1 aggregate/monomer mean fluorescence intensity (MFI) ratios were 0.45±0.06, 0.19±0.07, 0.12±0.03, 0.09±0.01, and 0.84±0.05, 0.66±0.13, 0.35±0.11, 0.27±0.02, which were different from the control group (0.67±0.15 and 0.97±0.42), and the differences were statistically significant ( F = 372.3, P < 0.05; F = 276.4, P < 0.05). Western blot was performed to detect different concentration of apatinib (2.5, 5.0 and 10.0 μmol/L) on the MV4-11 cells for 24 hours, the results showed that apatinib could down-regulate the phosphorylation of VEGFR2, Src and Stat3 in a dose-dependent manner. Conclusions:Apatinib can inhibit cell proliferation and induce apoptosis in AML with FLT3-ITD mutation. The possible mechanism is related to the down-regulation of phosphorylation of VEGFR2 and its downstream targets Src and Stat3.
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Follicular lymphoma (FL) is the most common indolent lymphoma. With the improvement of disease awareness and the introduction of various novel drugs, the 5-year overall survival rate has been more than 90% for the majority of FL patients. However, certain subgroups of FL patients, especially patients who progressed within 24 months after starting front-line therapy, still have worse outcome. This article reviews the progress in genetics, prognostic factors and treatment options of FL that reported at the 61st American Society of Hematology Annual Meeting 2019.
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Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma. The overall survival of FL is near 15 years. However, the survival would be significantly shortened in refractory, early-relapsed or transformed setting. The 60th American Society of Hematology (ASH) Annual Meeting reported several latest and optimal approaches to relapsed/refractory FL, with a focus on immune-based therapies and target agents for FL. This paper reviews and makes comments about these clinical trials.
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Objective To discover new biomarkers for diffuse large B-cell lymphoma (DLBCL) diagnosis and prognosis using nuclear magnetic resonance (NMR)-based serum metabolomics. Methods High-resolution serum 1H NMR spectra were collected from 7 DLBCL patients and 7 healthy controls. Spectra were processed using stoichiometry pattern-recognition methods [principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA)]. Results Significant difference (P <0.05) in 9 metabolites was observed between DLBCL and healthy control by OPLS-DA (variable interpretation rate R2Y ＝ 99.0 % and prediction rate Q2＝ 94.5 %). Compared with the healthy control group, higher levels of lactate (r ＝0.60, P<0.01), glycine (r ＝0.84, P<0.001), creatine (r ＝0.63, P<0.01), and choline (r ＝0.69, P< 0.01), lower levels of acetate (r＝ -0.88, P< 0.001), high-density lipoprotein (r＝ -0.77, P< 0.001), citrate (r ＝-0.82, P<0.001), glutamine (r ＝-0.53, P<0.05) and phosphocholine/glycerophosphocholine (r ＝-0.62, P<0.001) were detected in the serum samples of DLBCL. Conclusion The results of this study offer an evidence for significant changes between DLBCL patients and healthy people in serum metabolite profiles utilizing NMR-based serum metabolomics.
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<p><b>OBJECTIVE</b>To observe the clinical characteristics of infections in adult acute leukemia （AL）patients during chemotherapy in hospital, and identify the risk factors for infections.</p><p><b>METHODS</b>A retrospective study of patients with AL who underwent chemotherapy between July 2010 and Dec 2014 in the First Affiliated Hospital of Xiamen University was conducted. Clinical features and risk factors for infections were analyzed.</p><p><b>RESULTS</b>191 patients with AL received a total of 728 courses of chemotherapies. During these admissions, 385（52.9%) infections episodes occurred. The common infections sites were lower respiratory tract infection（36.3%，153/374）, bloodstream infection（17.1%, 64/374）, oral infection（13.6%，51/374）, and perianal infection（13.4%, 50/374）. 164 strains of pathogenic bacteria were detected. Gram- negative bacteria were recorded in 59.1% of documented pathogens, and Gram- positive bacteria were responsible for 32.9% of infections. Multivariate unconditioned logistic analysis of factors identified consistent independent risk factors for no completely remission（OR=0.142, P< 0.001）, duration of neutropenia longer than 7 days（OR=12.764, P<0.001）, general wards（OR=1.821, P< 0.001）, and hospitalization interval longer than 10 days（OR=0.720, P=0.039）.</p><p><b>CONCLUSION</b>Infections after chemotherapy for AL continues to be common. AL patients with induction chemotherapy or severe neutropenia faced an increased risk of infections by multivariate analysis. And patients with short-term stay or laminar flow wards seem to be less susceptible to infections.</p>
Subject(s)
Humans , Acute Disease , Bacterial Infections , Gram-Negative Bacteria , Gram-Positive Bacteria , Hospitals , Leukemia , Drug Therapy , Microbiology , Multivariate Analysis , Neutropenia , Remission Induction , Retrospective Studies , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To investigate the levels of tumor necrosis factor-α (TNF-α) in tissue or plasma and its clinical implications in different types of lymphoma.</p><p><b>METHODS</b>The levels of TNF-α in paraffin tissue or plasma samples were detected by immunohistochemistry or ELISA assay in 88 lymphoma patients and 88 healthy controls. Univariate and multivariate Cox regression analysis were used to identify the correlation between Ann Ardor stage, blood cells count, bone marrow abnormalities, erythrocyte sedimentation rate (ESR), serum ferritin and TNF-α expression.</p><p><b>RESULTS</b>The levels of TNF-α had significant difference in different types of lymphoma (P<0.05). High positive and levels in Hodgkin lymphoma [HL, 72.72% and (43.12±15.28) ng/L], aggressive non-HL [NHL, 67.86% and (40.73±16.65) ng/L], and indolent NHL [57.14% and (53.18±20.47) ng/L]. Cox regression analysis showed that Ann Ardor stage, bone marrow abnormalities, ESR, and the levels of TNF-α were independent risk factors for lymphoma with poor prognosis.</p><p><b>CONCLUSION</b>As an independent factor, TNF-α may play a role in the development of lymphoma and is an important prognostic factor.</p>
Subject(s)
Humans , Immunohistochemistry , Lymphoma , Prognosis , Risk Factors , Tumor Necrosis Factor-alphaABSTRACT
<p><b>OBJECTIVE</b>To investigate the incidence and risk factors for secondary cytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The clinical data of a total of 260 patients received allo-HSCT between Jan 1, 2006 to Jan 1, 2008 were retrospectively analyzed for the incidence and risk factors of secondary cytopenia. According to the hematopoietic reconstitution after transplantation, the patients were divided into (1) secondary neutropenia group; (2) secondary thrombocytopenia group and (3)secondary poor graft function group.</p><p><b>RESULTS</b>During the 100 days after allo-HSCT, the secondary neutropenia (38.8% vs 18.0%, P=0.0005) or secondary thrombocytopenia (25% vs 12%, P=0.01) occurred in haploidentical HSCT (haplo-HSCT) patients were more often than that in HLA-matched group. Poor graft function showed no significant difference between the above two groups (5.6% vs 2.0%, P=0.21). Multivariate analyses revealed that cytomegalovirus (CMV) infection significantly increased the risk of secondary neutropenia. GVHD and CMV infection were independent risk factors for secondary thrombocytopenia. Meanwhile, CMV infection was an independent risk factor for secondary poor graft function.</p><p><b>CONCLUSION</b>Secondary cytopenia remains a serious complication following allo-HSCT, especially in haplo-HSCT. Higher occurrence of GVHD and CMV infection may lead to higher incidence of secondary cytopenia in haplo-HSCT.</p>