Clinical outcomes and microenvironment profiling in relapsed/refractory multiple myeloma patients with extramedullary disease receiving anti-BCMA CAR T-cell-based therapy.

Relapsed/refractory multiple myeloma patients with extramedullary disease (EMD) have unfavorable prognosis and lack effective therapy. Chimeric antigen receptor (CAR) T-cell activities in EMD have yet to be determined; how EMD-specific microenvironment influences the clinical outcomes of CAR T-cell therapy remains of great interest. In this prospective cohort study, patients with histologically confirmed extra-osseous EMD were enrolled and treated with combined anti-BCMA and anti-CD19 CAR T-cell therapy from May 2017 to September 2023.

[A Retrospective Study of R±DHAX Regimen versus R-CHOP Regimen First-Line Treatment of Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma].

Objective: To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Methods: A total of 36 elderly patients with DLBCL who were admitted and treated with 3 of more courses of treatment from August 2011 to August 2021 were retrospectively analyzed, and they were divided into rituximab±DHAX (R±DHAX) regimen group (18 cases) and rituximab±CHOP (R-CHOP) regimen group (18 cases) according to the treatment plan, and clinical features, efficacy and survival of the patients were observed.

Results: Compared with R-CHOP group, patients of the R±DHAX group were older, and had worse performance status and higher IPI score, the differences between two groups in age, ECOG score and IPI score were statistically significant ( =0.

Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial.

Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells.

Autoimmune hemolytic anemia and thrombocytopenia in a Chinese patient with heterozygous NBAS mutations: Case report.

Rationale: Neuroblastoma amplified sequence (NBAS)-associated disease is an autosomal recessive disorder and a broad spectrum of clinical symptoms has been reported. However, autoimmune mediated hemolytic anemia (AIHA) is rarely reported in NBAS disease.

Patient Concerns: A now 21-year-old male harbors heterozygous variants of c.

Dysregulated CXCL12 expression in osteoblasts promotes B-lymphocytes preferentially homing to the bone marrow in MRL/lpr mice.

Todetect the abnormal distribution of B-lymphocytes between peripheral and bone marrow (BM) compartments and explore the mechanism of abnormal chemotaxis of B-lymphocytes in lupus subjects. The proportions of CXC chemokine receptor (CXCR)4 B cells and CFDA-labeled MRL/lpr-derived B cells were detected by flow cytometry. The levels of CXC chemokine ligand (CXCL)12in peripheral blood (PB)were measured by ELISA.

Case report: Deep molecular remissions post two separate CD19-targeted chimeric antigen receptor T-cell therapies do not prevent disease from relapsing in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is an aggressive B-cell malignancy. The management of a relapsed Ph+ ALL patient is challenging. Currently, either allogeneic stem cell transplant (allo-SCT) or CD19-targeted chimeric antigen receptor T-cell (CAR T-cell) are usually employed as salvage modalities for a relapsed patient.

Long-term analysis of cellular immunity in patients with RRMM treated with CAR-T cell therapy.

Chimeric antigen receptor T (CAR-T) cell therapy exhibits remarkable efficacy against refractory or relapsed multiple myeloma (RRMM); however, the immune deficiency following CAR-Ts infusion has not been well studied. In this study, 126 patients who achieved remission post-CAR-Ts infusion were evaluated for cellular immunity. Following lymphodepletion (LD) chemotherapy, the absolute lymphocyte count (ALC) and absolute counts of lymphocyte subsets were significantly lower than baseline at D0.

[Analysis of Related Factors of Autologous Peripheral Hematopoietic Stem Cell Mobilization in Patients with Lymphoma and Myeloma].

Objective: To explore the related factors affecting of autologous peripheral hematopoietic stem cell mobilization in patients with single center lymphoma and multiple myeloma.

Methods: The clinical total of 30 patients with lymphoma or multiple myeloma who underwent autologous peripheral hematopoietic stem cell mobilization and transplantation in the Affiliated Hospital of Jiangsu University from March 2012 to December 2021 were retrospectively analyzed, including the patients' age, gender, disease type, chemotherapy course, mobilization scheme, collection times, CD34 cell count, adverse events, days of neutrophil and platelet implantation after transplantation. The related factors affecting to the mobilization efficiency of peripheral blood stem cells was analyzed.

[The Effect of Doxycycline on the Expression of MMP-2 and MMP-9 in Multiple Myeloma].

Objective: To investigate the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in multiple myeloma (MM) patients, and analyze the effect of doxycycline (DOX) on the expression of MMP-2 and MMP-9 in MM cells.

Methods: The peripheral blood and bone marrow samples of MM patients were collected, and the patients were divided into three groups: newly diagnosed group, remission group and relapsed/refractory group, while the peripheral blood samples of 34 health people and the bone marrow samples of 17 IDA patients were selected as normal control and control group. The levels of MMP-2 and MMP-9 were detected by ELISA.

[Effect of Doxycycline on Intrinsic Apoptosis of Myeloma Cell Line H929 and Its Mechanism].

Objective: To investigate the mechanism of the in vitro toxicity of doxycycline to myeloma cell line H929 and also the possible pathway involved its toxicity.

Methods: Myeloma cell line H929 was treated with DOX, MEK inhibitor U0126 or RAS agonist ML-098, either alone or in combination. Then, the expression of p-MEK, caspase-3, caspase-9 and c-Jun in H929 were used to detected by Western blot; the cells proliferation and apoptosis were detected by CCK-8 assay and flow cytometry, respectively.

Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma.

Purpose: A combination of anti-B-cell maturation antigen (BCMA) and anti-CD19 chimeric antigen receptor (CAR) T cells induced high response rates in patients with relapsed or refractory (R/R) multiple myeloma (MM), but long-term outcomes have not been assessed yet.

Patients And Methods: In this single-arm, phase II trial, patients with R/R MM received a combination of anti-BCMA CAR T cells and anti-CD19 CAR T cells at a dose of 1 × 10 cells/kg, after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics.

Safety and efficacy of a humanized CD19 chimeric antigen receptor T cells for relapsed/refractory acute lymphoblastic leukemia.

CD19-targeted chimeric antigen receptor T (CAR-T) cells using murine single-chain variable fragment (scFv) has shown substantial clinical efficacy in treating relapsed/refractory acute lymphoblastic leukemia (R/R ALL). However, potential immunogenicity of the murine scFv domain may limit the persistence of CAR-T cells. In this study, we treated 52 consecutive subjects with R/R ALL with humanized CD19-specific CAR-T cells (hCART19s).

Bilateral anterior cerebral artery occlusion following CD19- and BCMA-targeted chimeric antigen receptor T-cell therapy for a myeloma patient.

Chimeric antigen receptor T (CAR-T)-cell therapy is a promising treatment for relapsed/refractory multiple myeloma (RRMM). In our previous report, CD19- and BCMA-targeted CAR-T co-administration was associated with a high response rate. Although cytokine release syndrome (CRS) and neurotoxicity are frequent complications following CAR-T treatment, cerebral infarction is rarely reported as a CAR-T-related complication.

[Up-Regulation of PI3K/Akt Signaling Pathway in H929 Cell Line by Doxycycline Not Beneficial to Its Anti-Myeloma Effect].

Objective: To investigate the effect and possible mechanism of up-regulation of p-Akt by doxycycline (DOX) on myeloma cell line H929.

Methods: Multiple myeloma cell line H929 was treated with DOX at different concentrations for different times, and cell proliferation rate was measured by CCK-8 assay. The protein expression level of p-Akt, PTEN, p-PDK1, p-mTOR, p-GSK-3β, and p-BAD was analyzed by Western blot.

A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial.

Background: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy has been shown to have activity in patients with relapsed or refractory multiple myeloma. Reports have suggested that a small subgroup of less differentiated myeloma clones express CD19 and anti-CD19 CAR T-cell therapy has shown activity in some of these patients. We aimed to assess the activity and safety of a combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma.

[Increment of N-cadherin Expression in Bone Marrow Mesenchymal Stem Cells Accompanies by Imparment of Bone Marrow B Lymphocyte Production in MRL/lpr Lupus Mice].

Objective: To investigate the hematological changes in MRL/lpr lupus mice and detect N-cadherin expression in their bone marrow mesenchymal stem cell (BMMSC).

Methods: Peripheral blood cell count was analyzed. The ratio of each lineage in bone marrow was analyzed by flow cytometry.

[IL-1β-Treated Bone Marrow Mesenchymal Stem Cells Enhances Osteogenetic Potential via NF-κB Pathway].

Unlabelled: Obsjective:To investigate the effects of differentaction time of IL-1β on the osteogenic capacity of bone marrow mensenchymal cells(BMMSC) and the role of nuclear factor-κB (NF-kB) pathway.

Methods: BMMSC isolated from normal donors was treated with IL-1β for 1 or 7 days, respectively. Alkaline phosphatase (ALP) and alizarin red(AR) stainings were used to detect the osteogenic differentiation potential of BMMSC.

[Clinical Efficacy of Decitabine Combined with Modified CAG Regimen for Relapse/Refractory Acute Myeloid Leukemia with AML1-ETO].

Objective: To investigate the clinical characteristics of patients with relapse-refractory acute myeloid leukemia(AML) with AML1-ETO, and therapeutic effcacy and side effects of decitabine combined with modified CAG regimen.

Methods: Clinical data of 8 cases of AML with AML1-ETO from June 2015 to January 2016 were analyzed retrospectively, including age, sex, initial symptoms, peripheral blood and bone marrow characteristics and so on. at the same time, the therapeutic effcacy and side effects of decitabine combined with modified CAG regimen were evaluated.

Predicting early post-chemotherapy adverse events in patients with hematological malignancies: a retrospective study.

Purpose: The purpose of this study was to develop a mathematical model that predicts the definite adverse events following chemotherapy in patients with hematological malignancies (HMs).

Methods: This is a retrospective cohort study including 1157 cases with HMs. Firstly, we screened and verified the independent risk factors associated with post-chemotherapy adverse events by both univariate and multivariate logistic regression analysis using 70 % of randomly selected cases (training set).

In vitro migratory aberrancies of mesenchymal stem cells derived from multiple myeloma patients only partially modulated by bortezomib.

Recent studies indicated that bone marrow mesenchymal stem cells (BM-MSCs) derived from multiple myeloma (MM) patients were different from those of normal subjects in a variety of aspects. However, it is largely unknown whether BM-MSCs derived from MM patients display any aberrant chemotactic migration. To this aim, we compared the chemotactic migration of BM-MSCs derived from MM patients with those from normal subjects.

Clinicopathologic analysis of POEMS syndrome and related diseases.

Background: POEMS syndrome, a rare paraneoplastic disease, is related to multiple organs, multiple systems, and multiple disciplines and can be mistaken for other disorders. Consequently, the diagnoses are often delayed. In this work we studied the clinicopathologic characteristics of the POEMS syndrome to improve early diagnosis to prevent irreversible damage.

[Effect of proteasome inhibitor on migration ability and hepatocyte growth factor expression of bone marrow mesenchymal stem cells in multiple myeloma patients].

This study was aimed to investigate the effect of proteasome inhibitor bortezomib on the migration ability and hepatocyte growth factor (HGF) expression of bone marrow mesenchymal stem cells (MSC) in multiple myeloma patients. Transwell assay was employed to measure the migration ability of bone marrow MSC in vitro before and after treatment with bortezomib. The HGF mRNA expression level was determined by real-time quantitative PCR.

[Proteasome inhibitor bortezomib inducing apoptosis of K562 cells not affected by bone marrow mesenchymal stem cells in vitro].

The study was aimed to investigate the effects of proteasome inhibitor bortezomib on the apoptosis of K562 cells in the presence of bone marrow mesenchymal stem cells, and explore its effect on expression of adhesion molecule VCAM-1 of both MSC and K562 cells. The K562 cells were co-cultured in direct contact with MSC, while the control cells were just cultured alone. Bortezomib was administered at a final concentration of 50 nmol/L.

[Chemotaxis-related factors are expressed abnormally in bone marrow mesenchymal stem cells of multiple myeloma patients].

This study was aimed to investigate the mRNA expression levels of hepatocyte growth factor (HGF), stromal cell-derived factor-1 (SDF-1), monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) in bone marrow mesenchymal stem cells (MSC) from multiple myeloma (MM) patients. The mRNA expression levels of HGF, SDF-1, MCP-1 and IL-8 in bone marrow MSC from 20 newly diagnosed MM patients were detected by real time quantitative RT-PCR and were compared with that in 9 controls. The results indicated that the mean mRNA expression level of HGF was up-regulated in MM patients, as compared with controls (p < 0.