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1.
Blood ; 143(23): 2344-2345, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842860
2.
Front Immunol ; 15: 1377546, 2024.
Article in English | MEDLINE | ID: mdl-38846938

ABSTRACT

Introduction: Multiple Myeloma (MM), a prevalent hematological malignancy, poses significant treatment challenges due to varied patient responses and toxicities to chemotherapy. This study investigates the predictive value of pretreatment serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) for chemotherapy-induced toxicities in newly diagnosed MM patients. We hypothesized that these cytokines, pivotal in the tumor microenvironment, might correlate with the incidence and severity of treatment-related adverse events. Methods: We conducted a prospective observational study with 81 newly diagnosed MM patients, analyzing serum cytokine levels using the multiplex cytometric bead assay (CBA) flow cytometry method. The study used non-parametric and multivariate analysis to compare cytokine levels with treatment-induced toxicities, including lymphopenia, infections, polyneuropathy, and neutropenia. Results: Our findings revealed significant associations between cytokine levels and specific toxicities. IL-8 levels were lower in patients with lymphopenia (p=0.0454) and higher in patients with infections (p=0.0009) or polyneuropathy (p=0.0333). VEGF concentrations were notably lower in patients with neutropenia (p=0.0343). IL-8 demonstrated an 81% sensitivity (AUC=0.69; p=0.0015) in identifying infection risk. IL-8 was an independent predictor of lymphopenia (Odds Ratio [OR]=0.26; 95% Confidence Interval [CI]=0.07-0.78; p=0.0167) and infection (OR=4.76; 95% CI=0.07-0.62; p=0.0049). High VEGF levels correlated with a 4-fold increased risk of anemia (OR=4.13; p=0.0414). Conclusions: Pre-treatment concentrations of IL-8 and VEGF in serum can predict hematological complications, infections, and polyneuropathy in patients with newly diagnosed MM undergoing chemotherapy. They may serve as simple yet effective biomarkers for detecting infections, lymphopenia, neutropenia, and treatment-related polyneuropathy, aiding in the personalization of chemotherapy regimens and the mitigation of treatment-related risks.


Subject(s)
Chemokine CCL2 , Interleukin-8 , Multiple Myeloma , Vascular Endothelial Growth Factor A , Humans , Multiple Myeloma/drug therapy , Multiple Myeloma/blood , Male , Female , Middle Aged , Aged , Vascular Endothelial Growth Factor A/blood , Interleukin-8/blood , Prognosis , Chemokine CCL2/blood , Interleukin-6/blood , Prospective Studies , Adult , Aged, 80 and over , Cytokines/blood , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
3.
Clin Transl Sci ; 17(5): e13828, 2024 May.
Article in English | MEDLINE | ID: mdl-38783568

ABSTRACT

As a treatment for relapsed or refractory multiple myeloma (MM), carfilzomib has been associated with a significant risk of cardiovascular adverse events (CVAE). The goals of our study were to evaluate the metabolomic profile of MM patients to identify those at high risk prior to carfilzomib treatment and to explore the mechanisms of carfilzomib-CVAE to inform potential strategies to protect patients from this cardiotoxicity. Global metabolomic profiling was performed on the baseline and post-baseline plasma samples of 60 MM patients treated with carfilzomib-based therapy, including 31 who experienced CVAE, in a prospective cohort study. Baseline metabolites and post-baseline/baseline metabolite ratios that differ between the CVAE and no-CVAE patients were identified using unadjusted and adjusted methods. A baseline metabolomic risk score was created to stratify patients. We observed a lower abundance of tauroursodeoxycholic acid (T-UDCA) in CVAE patients at baseline (odds ratio [OR] = 0.47, 95% confidence interval [CI] = 0.21-0.94, p = 0.044) compared with the no-CVAE patients. A metabolite risk score was able to stratify patients into three risk groups. The area under the receiver-operating curve of the model with clinical predictors and metabolite risk score was 0.93. Glycochenodeoxycholic acid (OR = 0.56, 95% CI = 0.31-0.87, p = 0.023) was significantly lower in post-baseline/baseline ratios of CVAE patients compared with no-CVAE patients. Following metabolomic analysis, we created a baseline metabolite risk score that can stratify MM patients into different risk groups. The result also provided intriguing clues about the mechanism of carfilzomib-CVAE and potential cardioprotective strategies.


Subject(s)
Cardiotoxicity , Metabolomics , Multiple Myeloma , Oligopeptides , Humans , Multiple Myeloma/drug therapy , Multiple Myeloma/blood , Oligopeptides/adverse effects , Male , Female , Aged , Middle Aged , Cardiotoxicity/etiology , Cardiotoxicity/blood , Cardiotoxicity/diagnosis , Metabolomics/methods , Prospective Studies , Metabolome/drug effects , Aged, 80 and over , Risk Factors
4.
Asian Pac J Cancer Prev ; 25(5): 1599-1605, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38809631

ABSTRACT

BACKGROUND: Multiple myeloma (MM) is the second most prevalent blood cancer after non-Hodgkin lymphoma. It is identified by the excessive production of abnormal monoclonal immunoglobulins, which can result in various clinical symptoms such as destructive bone lesions, renal dysfunction, anemia, and immunodeficiency. The current study aims to evaluate the serum levels of carboxy-terminal collagen crosslinks 1 (CTX-1), Fibulin-1, vitamin D3, LDH, and albumin in MM patients and their significance for early diagnosis. MATERIALS AND METHODS: This study included 30 healthy controls (11 males, 19 females) and 60 patients with multiple myeloma (37 males and 23 females), aged between 40-60 years. Five-milliliter blood samples were collected and stored at -20°C. Afterward, enzyme-linked immunosorbent assay (ELISA) kits were used to estimate the concentrations of CTX-1, Fibulin-1, and vitamin D3. Additionally, LDH and albumin levels were determined using the automated biochemistry analyzer. RESULTS: This study revealed that the majority of patients with multiple myeloma are between the ages of 51 and 60 years. The serum concentrations of CTX-1, Fibulin-1, and LDH were significantly increased in the multiple myeloma patients compared to the healthy control group. In contrast, the serum level of vitamin D3 was significantly decreased in patients with MM. CONCLUSION: Our results indicate that the incidence of multiple myeloma is higher in males than in females. Additionally, the serum concentrations of CTX-1 and Fibulin-1 were significantly higher in the multiple myeloma patients compared to the healthy control group, indicating their potential for early detection and as therapeutic targets.


Subject(s)
Biomarkers, Tumor , Calcium-Binding Proteins , Multiple Myeloma , Humans , Multiple Myeloma/blood , Female , Male , Middle Aged , Adult , Case-Control Studies , Calcium-Binding Proteins/blood , Biomarkers, Tumor/blood , Prognosis , Follow-Up Studies , Collagen Type I/blood , Peptides/blood , Peptide Fragments/blood
5.
J Clin Apher ; 39(3): e22114, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38708583

ABSTRACT

BACKGROUND: Stem cell apheresis in the context of autologous stem cell transplantation requires an accurate cluster of differentiantion 34 (CD34+) count determined by flow cytometry as the current gold standard. Since flow cytometry is a personnel and time-intensive diagnostic tool, automated stem cell enumeration may provide a promising alternative. Hence, this study aimed to compare automated hematopoietic progenitor enumeration carried out on a Sysmex XN-20 module compared with conventional flow cytometric measurements. METHODS: One hundred forty-three blood samples from 41 patients were included in this study. Correlation between the two methods was calculated over all samples, depending on leukocyte count and diagnosis. RESULTS: Overall, we found a high degree of correlation (r = 0.884). Furthermore, correlation was not impaired by elevated leukocyte counts (>10 000/µL, r = 0.860 vs <10 000/µL, r = 0.849; >20 000/µL, r = 0.843 vs <20 000/µL, r = 0.875). However, correlation was significantly impaired in patients with multiple myeloma (multiple myeloma r = 0.840 vs nonmyeloma r = 0.934). SUMMARY: Stem cell measurement carried out on the Sysmex XN-20 module provides a significant correlation with flow cytometry and might be implemented in clinical practice. In clinical decision-making, there was discrepancy of under 15% of cases. In multiple myeloma patients, XN-20 should be used with caution.


Subject(s)
Antigens, CD34 , Flow Cytometry , Hematopoietic Stem Cells , Adult , Female , Humans , Male , Antigens, CD34/analysis , Antigens, CD34/blood , Blood Cell Count/methods , Blood Cell Count/instrumentation , Flow Cytometry/methods , Hematopoietic Stem Cells/cytology , Leukocyte Count/methods , Multiple Myeloma/blood , Multiple Myeloma/diagnosis
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 499-504, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38660858

ABSTRACT

OBJECTIVE: To analyze the prognostic nutritional index (PNI), controlling nutritional status (CONUT) and fibrinogen/albumin ratio (FAR) levels in elderly patients with multiple myeloma (MM) and their prognostic impact. METHODS: The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed. The optimal cut-off values for PNI, CONUT score and FAR were obtained by receiver operating characteristic (ROC) curve, which were used for grouping patients. The correlation of above three indexes with clinical parameters such as sex, serum calcium (Ca), ß2-microglobulin (ß2-MG), serum creatinine (Cr) in elderly MM patients were analyzed. The survival rates of patients with different levels of each index were compared. Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed. RESULTS: The optimal cut-off values for PNI, CONUT score and FAR were 39.775, 3.5 and 0.175, respectively, according to which the patients were divided into high and low group. Statistical analysis showed that there were significant differences in albumin level among different groups (all P < 0.05). In addition, there was a significant difference in hemoglobin between high-PNI group and low-PNI group (P < 0.05), while in sex distribution between high-FAR and low-FAR group (P < 0.05). The survival rate of elderly MM patients with increased PNI, decreased CONUT score and FAR was higher (all P < 0.05). Univariate and multivariate analysis showed that ß2-MG, Cr, PNI, CONUT score and FAR were independent prognostic factors for elderly MM patients. CONCLUSION: PNI, CONUT score and FAR are related to some clinical indicators of elderly MM patients, and have an impact on the prognosis.


Subject(s)
Multiple Myeloma , Nutrition Assessment , Nutritional Status , Serum Albumin , Humans , Multiple Myeloma/blood , Prognosis , Aged , Retrospective Studies , Male , Serum Albumin/analysis , Female , Survival Rate , Fibrinogen/analysis , beta 2-Microglobulin/blood , Creatinine/blood
7.
Clin Biochem ; 127-128: 110761, 2024 May.
Article in English | MEDLINE | ID: mdl-38565341

ABSTRACT

OBJECTIVES: Some therapeutic monoclonal antibodies, like daratumumab and elotuzumab, produce interfering monoclonal bands on serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE). Whether other common therapeutic antibodies also produce interference has not been systematically evaluated. DESIGN AND METHODS: SPEP/IFE from patients receiving isatuximab (48 patients), belantamab mafodotin (BM; 41), and denosumab (41) were retrospectively reviewed for therapeutic antibody interference. Cases exhibiting isatuximab interference were quantified and the maximum duration of isatuximab effect was evaluated. To characterize band position, neat human serum was spiked with BM or denosumab at supratherapeutic concentrations. Band migration patterns were compared on SPEP and IFE, with band position expressed relative to other constant protein fractions. RESULTS: Isatuximab-induced IFE interference was common (81.3 % of evaluated patients) with a maximum observed duration of 8 weeks. 10.4 % of isatuximab patients had IgG kappa monoclonal gammopathies that co-migrated with the drug; this subset could benefit from HYDRASHIFT 2/4 isatuximab testing. 8.3 % of IFE cases were negative for an isatuximab band but showed large, endogenous M-spikes migrating elsewhere. All patients in this group expired within 1 year of this finding. We hypothesize that an inability to detect isatuximab in this setting corresponds to a large residual myeloma burden that reduces isatuximab serum concentration. This observation may serve as a negative prognostic factor. Spiking studies demonstrated that BM and denosumab produce interference in vitro, but sustained interference was not observed in >40 treated patients. CONCLUSIONS: Therapeutic antibody interference in patients receiving isatuximab is common, and can persist for at least 8 weeks after administration. >10 % of patients receiving isatuximab may benefit from HYDRASHIFT testing post-therapy. In contrast, BM and denosumab fail to produce sustained interference in treated patients.


Subject(s)
Antibodies, Monoclonal, Humanized , Denosumab , Multiple Myeloma , Humans , Denosumab/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Retrospective Studies , Multiple Myeloma/drug therapy , Multiple Myeloma/blood , Blood Protein Electrophoresis/methods , Female , Male , Aged , Middle Aged , Antibodies, Monoclonal , Immunoelectrophoresis/methods
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 493-498, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38660857

ABSTRACT

OBJECTIVE: To investigate the relationship between clinical indicators of CRAB symptoms and antioxidant enzyme activity in patients with multiple myeloma (MM). METHODS: The activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in the bone marrow supernatants of 44 patients with MM and 12 patients with non-malignant hematological diseases was detected by colorimetric assay, and then the differences in the activity of antioxidant enzymes between the two groups were compared. Furthermore, the relationship between the activity of antioxidant enzymes in the MM group and the levels of serum calcium, serum creatinine (Scr), hemoglobin (Hb), alkaline phosphatase (ALP) as well as bone lesions were analyzed. RESULTS: The antioxidant enzyme activity was lower in MM patients compared with the control group (P < 0.05). When the concentrations of serum calcium and ALP were higher than the normal levels, Hb was lower than 85 g/L, and there were multiple bone lesions, the activity of CAT, SOD and GPX was significantly declined (P < 0.05); When the concentration of Scr≥177 µmol/L, the activity of GPX was significantly declined (P < 0.05). Regression analyses showed that CAT, SOD and GPX were negatively correlated with serum calcium (r =-0.538, r =-0.456, r =-0.431), Scr (r =-0.342, r =-0.384, r =-0.463), and ALP (r =-0.551, r =-0.572, r =-0.482). CONCLUSION: The activity of antioxidant enzymes, including CAT, SOD and GPX, were decreased in patients with MM and they were negatively correlated with some clinical indicators of CRAB symptoms (such as serum calcium, Scr, and ALP), which suggests that promoting the activity of antioxidant enzymes may be beneficial to treat the CRAB symptoms of the patients with MM.


Subject(s)
Antioxidants , Multiple Myeloma , Humans , Alkaline Phosphatase/blood , Alkaline Phosphatase/metabolism , Antioxidants/metabolism , Bone Marrow , Brachyura , Calcium/blood , Calcium/metabolism , Catalase/blood , Catalase/metabolism , Creatinine/blood , Glutathione Peroxidase/blood , Glutathione Peroxidase/metabolism , Multiple Myeloma/blood , Multiple Myeloma/complications , Multiple Myeloma/enzymology , Multiple Myeloma/metabolism , Superoxide Dismutase/blood , Superoxide Dismutase/metabolism
9.
Int J Mol Sci ; 25(8)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38673940

ABSTRACT

Hepatic complications are an acknowledged cause of mortality and morbidity among patients undergoing hematopoietic stem cell transplantation. In this study, we aimed to evaluate the potential role in the prediction of liver injury of five selected microRNAs (miRNAs)-miR-122-5p, miR-122-3p, miR-15b-5p, miR-99b-5p, and miR-125a-5p-in the setting of autologous hematopoietic stem cell transplantation (ASCT). A total of 66 patients were included in the study: 50 patients (75.8%) with multiple myeloma (MM) and 16 (24.2%) with lymphoma. Blood samples were collected after the administration of the conditioning regimen, on the day of transplant (day 0). The expression levels of selected miRNAs were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using the miRCURY LNA miRNA Custom PCR Panels (QIAGEN). In a multivariate logistic regression analysis adjusted for age, sex, and the administered conditioning regimen, two miRNAs, hsa-miR-122-5p (odds ratio, OR 2.10, 95% confidence interval, CI: 1.29-3.42, p = 0.0029) and hsa-miR-125a-5p (OR 0.27, 95% CI: 0.11-0.71, p = 0.0079), were independent for hepatic toxicity occurrence during the 14 days after transplant. Our model in 10-fold cross-validation preserved its diagnostic potential with a receiver operating characteristics area under the curve (ROC AUC) of 0.75, 95% CI: 0.63-0.88 and at optimal cut-off reached 72.0% sensitivity and 74.4% specificity. An elevated serum level of miR-122-5p and decreased level of miR-125a-5p on day 0 are independent risk factors for hepatotoxicity in ASCT recipients, showing promise in accurately predicting post-ASCT complications. Identifying patients susceptible to complications has the potential to reduce procedure costs and optimize the selection of inpatient or outpatient procedures.


Subject(s)
Hematopoietic Stem Cell Transplantation , MicroRNAs , Transplantation, Autologous , Humans , MicroRNAs/blood , MicroRNAs/genetics , Male , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Middle Aged , Transplantation, Autologous/adverse effects , Adult , Aged , Multiple Myeloma/genetics , Multiple Myeloma/therapy , Multiple Myeloma/blood , Biomarkers/blood , ROC Curve , Lymphoma/blood , Lymphoma/genetics , Lymphoma/therapy
10.
Turk J Haematol ; 41(2): 83-90, 2024 05 30.
Article in English | MEDLINE | ID: mdl-38426298

ABSTRACT

Objective: Calprotectin (CLP), S100A6, and high mobility group nucleosome-binding protein 1 (HMGN1), known as alarmins, are involved in the pathogenesis of many tumors. In this study, we aimed to investigate the relationships of serum CLP, S100A6, and HMGN1 levels with the clinical and laboratory findings of patients with multiple myeloma (MM) and their roles in the pathogenesis of MM. Materials and Methods: We measured the serum CLP, S100A6, and HMGN1 levels of 55 newly diagnosed patients and 32 healthy controls using the sandwich enzyme-linked immunosorbent assay method. The medical records of the patients were also reviewed. Results: Serum CLP, S100A6, and HMGN1 levels were significantly decreased in MM patients compared to the control group (p=0.012, p=0.001, and p=0.030, respectively). Receiver operating characteristic analysis was used to determine diagnostic cut-off values for serum CLP, S100A6, and HMGN1 of <98 ng/mL (area under the curve [AUC]: 0.663, 95% confidence interval [CI]: 0.554-0.761, p=0.009), <1174.5 pg/mL (AUC: 0.706, 95% CI: 0.598-0.799, p=0.001), and <440.18 pg/mL (AUC: 0.640, 95% CI: 0.530-0.740, p=0.03), respectively. CLP levels were found to be statistically significantly higher in patients with light chain MM (91.58±22.57 ng/mL) compared to heavy chain MM (79.42±15.83 ng/mL) (p=0.03). A negative correlation was observed between CLP and M protein, immunoglobulin G, globulin, and beta-2 microglobulin (correlation coefficients: -0.361, -0.370, -0.279, -0.300, respectively; p=0.024, p=0.06, p=0.04, p=0.0033). Conclusion: In this study, we found that serum CLP, S100A6, and HMGN1 levels were statistically lower in patients with newly diagnosed MM compared to the control group. These results suggest that CLP may bind to the paraprotein produced by heavy chain MM in the blood, causing its blood levels to be low. Additionally, low levels of HMGN1, which is involved in DNA repair, suggest that HMGN1 may contribute to the complex genetic abnormalities found in cases of MM.


Subject(s)
Alarmins , Multiple Myeloma , Humans , Multiple Myeloma/blood , Multiple Myeloma/diagnosis , Female , Male , Middle Aged , Alarmins/blood , Aged , Leukocyte L1 Antigen Complex/blood , ROC Curve , Biomarkers, Tumor/blood , Case-Control Studies , HMGN1 Protein/blood , Adult , S100 Calcium Binding Protein A6/blood , Cell Cycle Proteins
11.
Leuk Lymphoma ; 65(6): 789-799, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38433500

ABSTRACT

As a promising alternative to bone marrow aspiration (BMA), mutational profiling on blood-derived circulating cell-free tumor DNA (cfDNA) is a harmless and simple technique to monitor molecular response and treatment resistance of patients with refractory/relapsed multiple myeloma (R/R MM). We evaluated the sensitivity and specificity of cfDNA compared to BMA CD138 positive myeloma plasma cells (PCs) in a series of 45 R/R MM patients using the 29-gene targeted panel (AmpliSeq) NGS. KRAS, NRAS, FAM46C, DIS3, and TP53 were the most frequently mutated genes. The average sensitivity and specificity of cfDNA detection were 65% and 97%, respectively. The concordance per gene between the two samples was good to excellent according to Cohen's κ coefficients interpretation. An increased number of mutations detected in cfDNA were associated with a decreased overall survival. In conclusion, we demonstrated cfDNA NGS analysis feasibility and accuracy in R/R MM patients who may benefit from early phase clinical trial.


Subject(s)
Biomarkers, Tumor , Circulating Tumor DNA , High-Throughput Nucleotide Sequencing , Multiple Myeloma , Mutation , Humans , Multiple Myeloma/genetics , Multiple Myeloma/diagnosis , Multiple Myeloma/mortality , Multiple Myeloma/blood , Male , Female , Middle Aged , Aged , Biomarkers, Tumor/genetics , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , High-Throughput Nucleotide Sequencing/methods , Cell-Free Nucleic Acids/genetics , Cell-Free Nucleic Acids/blood , Sensitivity and Specificity , Aged, 80 and over , Adult , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Drug Resistance, Neoplasm/genetics , DNA Mutational Analysis/methods , Prognosis , Reproducibility of Results
12.
Int J Lab Hematol ; 46(3): 495-502, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38379463

ABSTRACT

BACKGROUND: Detection of del(17p) in myeloma is generally performed by fluorescence in situ hybridization (FISH) on a slide with analysis of up to 200 nuclei. The small cell sample analyzed makes this a low precision test. We report the utility of an automated FISH method, called "immuno-flowFISH", to detect plasma cells with adverse prognostic risk del(17p) in bone marrow and blood samples of patients with myeloma. METHODS: Bone marrow (n = 31) and blood (n = 19) samples from 35 patients with myeloma were analyzed using immuno-flowFISH. Plasma cells were identified by CD38/CD138-immunophenotypic gating and assessed for the 17p locus and centromere of chromosome 17. Cells were acquired on an AMNIS ImageStreamX MkII imaging flow cytometer using INSPIRE software. RESULTS: Chromosome 17 abnormalities were identified in CD38/CD138-positive cells in bone marrow (6/31) and blood (4/19) samples when the percent plasma cell burden ranged from 0.03% to 100% of cells. Abnormalities could be identified in 14.5%-100% of plasma cells. CONCLUSIONS: The "immuno-flowFISH" imaging flow cytometric method could detect del(17p) in plasma cells in both bone marrow and blood samples of myeloma patients. This method was also able to detect gains and losses of chromosome 17, which are also of prognostic significance. The lowest levels of 0.009% (bone marrow) and 0.001% (blood) for chromosome 17 abnormalities was below the detection limit of current FISH method. This method offers potential as a new means of identifying these prognostically important chromosomal defects, even when only rare cells are present and for serial disease monitoring.


Subject(s)
Chromosomes, Human, Pair 17 , Flow Cytometry , In Situ Hybridization, Fluorescence , Multiple Myeloma , Plasma Cells , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/genetics , Multiple Myeloma/blood , Multiple Myeloma/pathology , Plasma Cells/pathology , Flow Cytometry/methods , Chromosomes, Human, Pair 17/genetics , Male , Female , Aged , Middle Aged , Bone Marrow/pathology , Chromosome Deletion , Aged, 80 and over , Immunophenotyping , Adult
13.
Cytometry B Clin Cytom ; 106(3): 162-170, 2024 05.
Article in English | MEDLINE | ID: mdl-38418432

ABSTRACT

Chimeric antigen receptor (CAR) modified T cell therapies targeting BCMA have displayed impressive activity in the treatment of multiple myeloma. There are currently two FDA licensed products, ciltacabtagene autoleucel and idecabtagene vicleucel, for treating relapsed and refractory disease. Although correlative analyses performed by product manufacturers have been reported in clinical trials, there are limited options for reliable BCMA CAR T detection assays for physicians and researchers looking to explore it as a biomarker for clinical outcome. Given the known association of CAR T cell expansion kinetics with toxicity and response, being able to quantify BCMA CAR T cells routinely and accurately in the blood of patients can serve as a valuable asset. Here, we optimized an accurate and sensitive flow cytometry test using a PE-conjugated soluble BCMA protein, with a lower limit of quantitation of 0.19% of CD3+ T cells, suitable for use as a routine assay for monitoring the frequency of BCMA CAR T cells in the blood of patients receiving either ciltacabtagene autoleucel or idecabtagene vicleucel.


Subject(s)
B-Cell Maturation Antigen , Flow Cytometry , Immunotherapy, Adoptive , Multiple Myeloma , Receptors, Chimeric Antigen , Humans , Flow Cytometry/methods , B-Cell Maturation Antigen/immunology , Receptors, Chimeric Antigen/immunology , Immunotherapy, Adoptive/methods , Multiple Myeloma/immunology , Multiple Myeloma/diagnosis , Multiple Myeloma/blood , T-Lymphocytes/immunology
14.
Ann Hematol ; 103(6): 1979-1987, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38206369

ABSTRACT

1q21+ is a common cytogenetic abnormality in multiple myeloma (MM) and is considered an independent predictor of poor prognosis; however, its impact on extramedullary disease (EMD) remains unknown. Our study reviewed the clinical relevance and prognostic value of 1q21+ status in 92 patients with NDMM and EMD. 1q21+ was detected in 23.9% (22/92) of patients. Patients with 1q21+ presented with advanced International Staging System stages (P = 0.006), lower level of hemoglobin (P = 0.004), higher percentage of plasma cells in the bone marrow (P < 0.001), higher level of serum ß2-microglobulin (7.24 g/L vs. 3.85 g/L, P = 0.003), and higher levels of lactic dehydrogenase (LDH) (206.5 U/L vs. 177 U/L, P = 0.019). The prevalence of soft tissue-related EMD (EMD-S) (54.5% vs. 18.6%, P < 0.001), renal dysfunction (50.5% vs. 17.7%, P = 0.002), and hypercalcemia (27.3% vs. 7.1%, P = 0.011) was also higher. 1q21+ was strongly associated with other high-risk cytogenetic abnormalities, including IgH/FGFR3 (22.7% vs. 4.3%, P = 0.007) and IgH/MAF translocations (22.7% vs. 1.4%, P < 0.001). 1q21+ patients had significantly shorter overall survival (OS) and progression-free survival (PFS) (OS: 24 months vs. 47 months, P = 0.002; PFS: 14 months vs. 38 months, P < 0.001); the poor survival outcomes could not be reversed by autologous hematopoietic stem cell transplantation. Multivariate analysis suggested that 1q21+ , EMD-S, elevated lactate dehydrogenase (LDH) levels, and P53 deletion were independent risk factors for poor prognosis in patients with EMD. In patients with 1q21+ EMD, hypercalcemia, elevated LDH levels, and P53 deletion were independent adverse risk prognostic factors.


Subject(s)
Chromosomes, Human, Pair 1 , Multiple Myeloma , Humans , Multiple Myeloma/mortality , Multiple Myeloma/diagnosis , Multiple Myeloma/blood , Male , Female , Middle Aged , Retrospective Studies , Aged , Chromosomes, Human, Pair 1/genetics , Adult , Prognosis , Chromosome Aberrations , Aged, 80 and over , Survival Rate
15.
Cancer ; 130(10): 1884-1893, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38236717

ABSTRACT

BACKGROUND: The presence of circulating plasma cells (CPCs) is an important laboratory indicator for the diagnosis, staging, risk stratification, and progression monitoring of multiple myeloma (MM). Early detection of CPCs in the peripheral blood (PB) followed by timely interventions can significantly improve MM prognosis and delay its progression. Although the conventional cell morphology examination remains the predominant method for CPC detection because of accessibility, its sensitivity and reproducibility are limited by technician expertise and cell quantity constraints. This study aims to develop an artificial intelligence (AI)-based automated system for a more sensitive and efficient CPC morphology detection. METHODS: A total of 137 bone marrow smears and 72 PB smears from patients with at Zhongshan Hospital, Fudan University, were retrospectively reviewed. Using an AI-powered digital pathology platform, Morphogo, 305,019 cell images were collected for training. Morphogo's efficacy in CPC detection was evaluated with additional 184 PB smears (94 from patients with MM and 90 from those with other hematological malignancies) and compared with manual microscopy. RESULTS: Morphogo achieved 99.64% accuracy, 89.03% sensitivity, and 99.68% specificity in classifying CPCs. At a 0.60 threshold, Morphogo achieved a sensitivity of 96.15%, which was approximately twice that of manual microscopy, with a specificity of 78.03%. Patients with CPCs detected by AI scanning had a significantly shorter median progression-free survival compared with those without CPC detection (18 months vs. 34 months, p< .01). CONCLUSIONS: Morphogo is a highly sensitive system for the automated detection of CPCs, with potential applications in initial screening, prognosis prediction, and posttreatment monitoring for MM patients. PLAIN LANGUAGE SUMMARY: Diagnosing and monitoring multiple myeloma (MM), a type of blood cancer, requires identifying and quantifying specific cells called circulating plasma cells (CPCs) in the blood. The conventional method for detecting CPCs is manual microscopic examination, which is time-consuming and lacks sensitivity. This study introduces a highly sensitive CPC detection method using an artificial intelligence-based system, Morphogo. It demonstrated remarkable sensitivity and accuracy, surpassing conventional microscopy. This advanced approach suggests that early and accurate CPC detection is achievable by morphology examination, making efficient CPC screening more accessible for patients with MM. This innovative system has the potential to be used in the diagnosis and risk assessment of MM.


Subject(s)
Deep Learning , Multiple Myeloma , Plasma Cells , Humans , Multiple Myeloma/pathology , Multiple Myeloma/blood , Multiple Myeloma/diagnosis , Plasma Cells/pathology , Retrospective Studies , Female , Male , Middle Aged , Aged , Neoplastic Cells, Circulating/pathology , Prognosis , Adult
16.
Nephron ; 148(6): 399-407, 2024.
Article in English | MEDLINE | ID: mdl-38113858

ABSTRACT

INTRODUCTION: Multiple myeloma (MM) frequently involves the kidneys, resulting in acute, subacute, or chronic kidney disease (CKD). Patient- and treatment-related factors are associated with the long-term development of CKD. The aim of our study was to examine the association of serum free light chain (FLC) levels, measured at the time of diagnosis of MM, and CKD at subsequent follow-up. METHODS: Patients with newly diagnosed MM were identified using cancer registries at five hospitals. The primary outcome was low eGFR (<60 mL/min/1.73 m2) or dialysis dependence and a secondary composite outcome of low eGFR, dialysis dependence, or death at the last follow-up, up to 12 months from diagnosis. Logistic regression analyses were performed. RESULTS: A total of 149 patients met the inclusion criteria. Patients with an FLC level above the median had a higher frequency of hypertension (54% vs. 81%; p < 0.001), hyperlipidemia (37% vs. 56%; p = 0.018), low eGFR at the time of diagnosis (43% vs. 66%; p = 0.006), and a higher MM stage (p = 0.018). On multivariable analyses, after adjustment for several covariates, serum FLC level (per each 100 mg/L) was independently associated with low eGFR or dialysis dependence at follow-up (adjusted odds ratio [aOR] 1.021; 95% CI: 1.002, 1.041; p = 0.033). This association persisted for the composite outcome of low eGFR, dialysis dependence, or death (aOR 1.034; 95% CI: 1.006, 1.063; p = 0.018). DISCUSSION/CONCLUSION: Higher serum FLC level measured at the time of MM diagnosis is independently associated with CKD at up to 12 months of follow-up.


Subject(s)
Glomerular Filtration Rate , Immunoglobulin Light Chains , Multiple Myeloma , Renal Insufficiency, Chronic , Humans , Multiple Myeloma/blood , Multiple Myeloma/diagnosis , Male , Female , Aged , Middle Aged , Immunoglobulin Light Chains/blood , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/diagnosis , Aged, 80 and over , Kidney/physiopathology , Renal Dialysis
17.
Curr Med Sci ; 43(4): 679-688, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37326888

ABSTRACT

OBJECTIVE: Metabolic disorders are regarded as hallmarks of multiple myeloma (MM) and are responsible for rapid cancer cell proliferation and tumor growth. However, the exact biological roles of metabolites in MM cells have not been fully explored. This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid (Lac) in the proliferation of myeloma cells and cell sensitivity to bortezomib (BTZ). METHODS: Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients. The CCK8 assay and flow cytometry were used to detect cell proliferation, apoptosis, and cell cycle changes. Western blotting was used to detect the potential mechanism and apoptosis- and cycle-related protein changes. RESULTS: Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients. It was significantly correlated with Durie-Salmon Staging (DS Staging) and the International Staging System (ISS Staging) and the serum and urinary involved/uninvolved free light chain ratios. Patients with relatively high lactate levels had a poor treatment response. Moreover, in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells, which was accompanied by an increased proportion of S-phase cells. In addition, Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2 (NFkB2) and RelB. CONCLUSION: Metabolic changes are important in MM cell proliferation and treatment response; lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.


Subject(s)
Antineoplastic Agents , Bortezomib , Drug Resistance, Neoplasm , Lactic Acid , Multiple Myeloma , Adult , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Bortezomib/pharmacology , Bortezomib/therapeutic use , Cell Cycle Proteins/metabolism , Cell Line, Tumor/drug effects , Cell Line, Tumor/metabolism , Cell Proliferation/drug effects , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/physiology , Lactic Acid/blood , Lactic Acid/metabolism , Lactic Acid/pharmacology , Metabolome , Multiple Myeloma/blood , Multiple Myeloma/drug therapy , Multiple Myeloma/metabolism , Prognosis
18.
Blood Cancer Discov ; 3(6): 478-480, 2022 11 02.
Article in English | MEDLINE | ID: mdl-36026510

ABSTRACT

In this issue of Blood Cancer Discovery, Dhodapkar and colleagues find that myeloid, dendritic, and endogenous T-cell populations in the bone marrow microenvironment are associated with progression-free survival (PFS) in multiple myeloma patients responding to B-cell maturation antigen-targeted CAR T cells. Immunosuppressive myeloid cells are associated with short PFS, but a diverse T-cell receptor repertoire and more dendritic cells are associated with a longer PFS, suggesting a potential role for epitope spreading. See related article by Dhodapkar et al., p. 490 (6).


Subject(s)
Bone Marrow Neoplasms , Multiple Myeloma , Receptors, Chimeric Antigen , Humans , B-Cell Maturation Antigen/immunology , Multiple Myeloma/blood , Bone Marrow/immunology , T-Lymphocytes/immunology , Tumor Microenvironment
19.
Hematology ; 27(1): 778-784, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35793786

ABSTRACT

BACKGROUND/OBJECTIVE: Bone marrow biopsy, the gold standard for the diagnosis of multiple myeloma (MM), has main limitation of the invasiveness. Here, we explored the diagnostic and prognostic values of circulating miR-1246 in patients with MM. MATERIAL AND METHODS: Ninety MM patients and 30 healthy donors (control group) were recruited in this study. The expression of miR-1246 in the peripheral blood samples was detected using qPCR. The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of miR-1246 in MM. The Kaplan-Meier survival analyze was performed to evaluate the prognostic value of miR-1246. RESULTS: The expression level of serum miR-1246 from newly diagnosed MM patients was significantly higher than that of the control group. Circulating miR-1246 level was decreased after treatment in remission patients, but remained high levels in relapsed patients (P < 0.05). ROC analysis demonstrated that miR-1246 showed a high diagnostic value in MM with an area under the curve (AUC) of 0.952, the sensitivity of 87%, and the specificity of 95% [95% confidence interval (CI) 0.902-1.007; P < 0.001]. Kaplan-Meier analysis showed that the progression-free survival (PFS) (14.0 months vs. 26.5 months, P = 0.045) and overall survival (OS) (20.5 months vs. 55.5 months, P = 0.014) were significantly shorter in patients with high miR-1246 expression as compared with those in patients with miR-1246 low expression. Multiple Cox regression model analysis showed that circulating miR-1246 was an independent prognostic factor for PFS (HR 2.786, 95% CI: 1.420-5.467, P = 0.003) and OS (HR 2.995, 95% CI: 1.166-7.689, P = 0.023) in MM patients. CONCLUSION: This study demonstrates that circulating miR-1246 level is elevated in MM patients, which shows high values in the diagnosis and prognosis prediction in patients with MM.


Subject(s)
MicroRNAs , Multiple Myeloma , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Humans , Kaplan-Meier Estimate , MicroRNAs/blood , MicroRNAs/genetics , Multiple Myeloma/blood , Multiple Myeloma/diagnosis , Multiple Myeloma/genetics , Prognosis
20.
BMC Endocr Disord ; 22(1): 29, 2022 Jan 25.
Article in English | MEDLINE | ID: mdl-35073877

ABSTRACT

BACKGROUND: Adipocytes and their products, adipocytokines, play important roles in the generation and development of multiple myeloma (MM). Studies have demonstrated some adipocytokines to be associated with MM, although those results are controversial. Therefore, we conducted a meta-analysis to verify the association of adipocytokines with MM. METHODS: We performed a systematic retrieval of literature published prior to 26 October 2021. Standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated to evaluate pooled effects. Subgroup analysis and meta-regression analysis were conducted to detect sources of heterogeneity. Sensitivity analysis was performed to evaluate the stability of the study. Publication bias was assessed by funnel plots and Egger's linear regression test. RESULTS: Ten eligible studies with 1269 MM patients and 2158 controls were included. The pooled analyses indicated that circulating leptin levels of MM patients were significantly higher than control levels (SMD= 0.87, 95%CI: 0.33 to 1.41), while the circulating adiponectin levels in MM patients were significantly lower than controls with a pooled SMD of -0.49 (95%CI: -0.78 to -0.20). The difference of circulating resistin levels were not significant between MM patients and controls (SMD= -0.08, 95%CI: -0.55 to 0.39). Subgroup analysis and meta-regression analysis found that sample size, age, and sex were possible sources of heterogeneity. Sensitivity analysis demonstrated our pooled results to be stable. CONCLUSION: Decreased circulating adiponectin and increased leptin levels were associated with the occurrence and development of MM. Adiponectin and leptin may be potential biomarkers and therapeutic targets for MM.


Subject(s)
Adipokines/blood , Multiple Myeloma/blood , Biomarkers, Tumor/blood , Case-Control Studies , Humans
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