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Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the role of serum adenosine deaminase (ADA) combined with globulin (GLB), creatinine (CREA), β-microglobulin (β-MG) and hemoglobin (HGB) in the initial...
OBJECTIVE
To investigate the role of serum adenosine deaminase (ADA) combined with globulin (GLB), creatinine (CREA), β-microglobulin (β-MG) and hemoglobin (HGB) in the initial screening of multiple myeloma (MM), in order to reduce missed diagnosis and misdiagnosis of MM.
METHODS
A retrospective analysis was performed on 62 newly diagnosed multiple myeloma (NDMM) patients who were admitted to the Department of Hematology of the First Affiliated Hospital of Chengdu Medical College from April 2018 to December 2021, and 33 patients with benign hematologic diseases and 30 healthy subjects were selected as the control group. The expression of ADA in pan-cancer was analyzed using TCGA and GTEx databases. The general data and laboratory indicators of the subjects were collected, and the differences of ADA activity and other laboratory indicators in each group were compared. The relationship between serum ADA activity and clinical data of NDMM patients was analyzed. The changes of ADA activity before and after chemotherapy in NDMM patients and the differences of ADA activity in NDMM patients with different DS and ISS stages were compared. Multivariate logistic regression was used to analyze the risk factors of NDMM. The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of ADA and other laboratory indicators in MM. Bioinformatics method was used to analyze the co-expression networks and enrichment pathways of ADA.
RESULTS
ADA level was significantly upregulated in tissues of 14 types of cancer in TCGA database, and ADA was highly expressed in 11 types of cancer in TCGA combined with GTEx databases. The serum levels of ADA, GLB, uric acid (UA), cystatin C (CysC) and β-MG in the NDMM group were significantly higher than those in benign hematologic disease group and healthy control group ( < 0.05), while the levels of ALB and the value of albumin to globulin ratio (A∶G) in the NDMM group were significantly lower than those in the other two groups ( < 0.001). There were significant differences in DS stage ( =0.036), ISS stage ( =0.019) and the levels of CREA ( =0.036), UA ( =0.034), β-MG ( =0.019) in NDMM patients with different ADA activity levels. After primary chemotherapy, ADA activity and β-MG concentration were decreased in NDMM patients ( < 0.01). The comparison results of patients in different stages showed that ADA activity of patients in DS stage I+II was significantly lower than that of patients in DS stage III ( <0.05), and ADA activity of patiens in ISS stage I+II was significantly lower than that of patients in ISS stage III ( < 0.01). Multivariate logistic regression analysis showed that increased GLB, increased ADA activity, increased CREA, increased β-MG and decreased HGB were independent risk factors for NDMM. The area under the curve (AUC) of ADA in the diagnosis of MM was 0.847, and the AUC of ADA combined with GLB, CREA, β-MG and HGB in the diagnosis of MM was 0.940. The results of co-expression network and enrichment pathway analysis showed that ADA bounded to 20 proteins and it was significantly associated with the metabolic pathways of purine, pyrimidine, nicotinate and nicotinamide.
CONCLUSION
The detection of ADA activity in serum is of positive significance for the auxiliary diagnosis, therapeutic evaluation and monitoring the progress of NDMM patients. ADA combined with GLB, CREA, β-MG and HGB can improve the detection rate of MM, and reduce missed diagnosis and misdiagnosis to a certain extent.
Topics: Humans; Adenosine Deaminase; Multiple Myeloma; beta 2-Microglobulin; Retrospective Studies; Creatinine; Hemoglobins; Male; Female; Clinical Relevance
PubMed: 38926967
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.019 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM) with mSMART 3.0...
OBJECTIVE
To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM) with mSMART 3.0 score.
METHODS
Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023, all of whom received daltezumab-based regimen (regimen drugs including dexamethasone, isazomib, bortezomib, lenalidomide). The efficacy and safety of the treatment were retrospectively analyzed.
RESULTS
The median age of 16 patients was 63.5 (47-70) years old, including 10 cases of IgG type, 2 cases of IgA type, and 4 cases of light chain type. The curative efficacy was judged in all 16 patients, with an overall response rate of 93.75% (15/16), including 4 cases of strict complete remission (sCR), 1 case of complete remission (CR), 2 case of very good partial remission (VGPR), partial remission (PR) in 5 cases, and minor remission (MR) in 3 cases. The median follow-up time was 11(2-30) months, and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period. The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia, and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections.
CONCLUSION
Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.
Topics: Humans; Multiple Myeloma; Middle Aged; Aged; Antineoplastic Combined Chemotherapy Protocols; Male; Retrospective Studies; Female; Antibodies, Monoclonal; Dexamethasone; Treatment Outcome; Antibodies, Monoclonal, Humanized; Lenalidomide; Bortezomib
PubMed: 38926966
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.018 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To analyze the prognostic value of del(1p32) in patients with newly diagnosed multiple myeloma (MM).
OBJECTIVE
To analyze the prognostic value of del(1p32) in patients with newly diagnosed multiple myeloma (MM).
METHODS
The clinical data of 341 newly diagnosed MM attended in Jiangsu Province Hospital were retrospective analyzed. Clinical characteristic combined with genetic features, especially del(1p32), were analyzed for survival and prognostic of patients.
RESULTS
Among the 341 patients with newly diagnosed MM, 24(7.0%) patients were del(1p32) positive. The progression-free survival (PFS) and overall survival (OS) were significantly shorter in MM patients with del(1p32) than those without del(1p32) (PFS: < 0.001;OS: < 0.001). The COX proportional-hazards model showed that del (1p32) was an independent risk factor for PFS and OS of patients with MM. The patients with both 1q21 gain/amplification and del(1p32), as "double-hit chromosome 1", have worse prognosis than those with only 1q21 gain/amplification or only del(1p32) (PFS: < 0.001; OS: < 0.001).
CONCLUSION
Del(1p32) is an independent risk factor for PFS and OS of patients with MM. Del(1p32) detection should be widely used in the prognostic analysis for newly diagnosed MM patients.
Topics: Humans; Multiple Myeloma; Prognosis; Retrospective Studies; Chromosomes, Human, Pair 1; Risk Factors; Chromosome Deletion; Proportional Hazards Models; Male; Female; Middle Aged
PubMed: 38926965
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.017 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Jun 2024To investigate the efficacy and safety of daratumumab based regimens in relapse and/or refractory multiple myeloma (RRMM) in the real world, as well as the impact of...
OBJECTIVE
To investigate the efficacy and safety of daratumumab based regimens in relapse and/or refractory multiple myeloma (RRMM) in the real world, as well as the impact of daratumumab on stem cell collection and engraftment.
METHODS
The clinical data of patients with RRMM who received daratumumab in hematology department of the First Affiliated Hospital of Xiamen University from February 2019 to March 2023 and had evaluable efficacy were retrospective analysis.
RESULTS
All 43 RRMM patients were treated with daratumumab-based combination regimens, including Dd, DVd, DRd, Dkd, DId, and Dara-DECP. With median follow-up time 10.1 (2.1-36.6) months, the best overall response rate (ORR) was 74.4% and a best complete response rate (CR) was 25.6%. 1-year overall survival rate (OS) was 84.5%. The most common severe hematologic adverse events (Grade>3) are 3/4 grade leukopenia(18.6%), and the most common severe non-hematologic adverse events were infusion-related reactions (IRRs, 20.9%) and infections(7.0%). Multivariate prognostic analysis showed that extramedullary infiltration was an independent adverse prognostic factor affecting OS ( =0.004). The use of daratumumab has no effect on stem cell collection, or engraftment.
CONCLUSION
Daratumumab is safe and effective in RRMM.
Topics: Humans; Multiple Myeloma; Antibodies, Monoclonal; Retrospective Studies; Survival Rate; Antineoplastic Combined Chemotherapy Protocols; Recurrence; Male; Female; Middle Aged; Treatment Outcome
PubMed: 38926964
DOI: 10.19746/j.cnki.issn.1009-2137.2024.03.016 -
BMJ Case Reports Jun 2024Multiple myeloma is a rare haematological malignancy characterised by the clonal proliferation of plasma cells within the bone marrow. Typical manifestations include...
Multiple myeloma is a rare haematological malignancy characterised by the clonal proliferation of plasma cells within the bone marrow. Typical manifestations include bone pain, fatigue and monoclonal protein elevation in serum and urine. Less than 1% of cases develop myelomatous pleural effusion, a severe complication indicative of advanced disease and a very poor prognosis.Here, we present a case of a woman with a new diagnosis of multiple myeloma complicated by bilateral myelomatous pleural effusions as the initial presentation. This case underscores the diverse clinical spectrum of multiple myeloma, the significance of timely diagnosis and the threatening implications associated with myelomatous pleural effusions.
Topics: Humans; Multiple Myeloma; Female; Pleural Effusion, Malignant; Middle Aged; Aged; Pleural Effusion
PubMed: 38925672
DOI: 10.1136/bcr-2023-258935 -
Tierarztliche Praxis. Ausgabe K,... Jun 2024An acute, unilateral othematoma was diagnosed in a 9-year-old mixed-breed dog. There was no clinical or anamnestic evidence for the cause of the othematoma. During...
An acute, unilateral othematoma was diagnosed in a 9-year-old mixed-breed dog. There was no clinical or anamnestic evidence for the cause of the othematoma. During diagnostic work-up, marked hyperglobulinemia and marked thrombocytopenia were detected. This was a consequence of a multiple myeloma. This is the first case report of a dog with othematoma secondary to coagulopathy associated with multiple myeloma.
Topics: Dogs; Animals; Multiple Myeloma; Dog Diseases; Hematoma; Male; Thrombocytopenia
PubMed: 38925136
DOI: 10.1055/a-2324-0508 -
The New England Journal of Medicine Jun 2024
Review
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Immunoglobulin Light Chains; Amyloidosis; Male
PubMed: 38924733
DOI: 10.1056/NEJMra2304088 -
Journal of Cellular and Molecular... Jun 2024Despite remarkable advancements in the treatment of multiple myeloma (MM), relapse remains a challenge. However, the mechanisms underlying this disease remain unclear....
Despite remarkable advancements in the treatment of multiple myeloma (MM), relapse remains a challenge. However, the mechanisms underlying this disease remain unclear. This study aimed to identify potential biomarkers that could open new avenues for MM treatment. Microarray data and clinical characteristics of patients with MM were obtained from the Gene Expression Omnibus database. Differential expression analysis and protein-protein interaction (PPI) network construction were used to identify hub genes associated with MM. Predictive performance was further assessed using receiver operating characteristic curves and nomogram construction. Functional enrichment analysis was conducted to investigate possible mechanisms. Mendelian randomization (MR) was used to evaluate the causal relationship between the crucial gene and MM risk. Topological analysis of the PPI network revealed five hub genes associated with MM, with myeloperoxidase (MPO) being the key gene owing to its highest degree and area under the curve values. MPO showed significant differences between patients with MM and controls across all datasets. Functional enrichment analysis revealed a strong association between MPO and immune-related pathways in MM. MR analysis confirmed a causal relationship between MPO and the risk of MM. By integrating microarray analysis and MR, we successfully identified and validated MPO as a promising biomarker for MM that is potentially implicated in MM pathogenesis and progression through immune-related pathways.
Topics: Multiple Myeloma; Humans; Mendelian Randomization Analysis; Protein Interaction Maps; Biomarkers, Tumor; Peroxidase; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Gene Regulatory Networks; ROC Curve; Microarray Analysis; Nomograms
PubMed: 38923838
DOI: 10.1111/jcmm.18504 -
Cancer Medicine Jun 2024Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a potent treatment for relapsed or refractory multiple myeloma, demonstrating significant clinical... (Review)
Review
BACKGROUND
Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a potent treatment for relapsed or refractory multiple myeloma, demonstrating significant clinical efficacy. Despite these advances, treatment-related toxicities, particularly infections, pose a significant challenge to patient safety.
METHODS
This review synthesizes current knowledge on the mechanisms underlying post-CAR-T therapy infections, focusing on the interplay between immune dysfunction, host factors, and treatment-induced toxicity. It provides a comprehensive analysis of the temporal and individual variability in infection characteristics and the confounding clinical presentation of cytokine release syndrome.
RESULTS
The review identifies that patients receiving CAR-T cells are at increased risk of concurrent infections due to the heterogeneity in infection characteristics across different time periods, individuals, and patient groups. It highlights the diagnostic and therapeutic complexities introduced by the overlapping symptoms of infection and cytokine release syndrome.
CONCLUSION
To enhance the infection control post-CAR-T therapy, this review proposes preventive strategies tailored to the early and long-term management of patients. It underscores the need for a nuanced understanding of infection mechanisms and the importance of personalized prevention plans to improve clinical outcomes in multiple myeloma treatment.
Topics: Humans; Multiple Myeloma; Immunotherapy, Adoptive; Cytokine Release Syndrome; Receptors, Chimeric Antigen; Infections; Risk Factors
PubMed: 38923216
DOI: 10.1002/cam4.7372 -
Annals of the Academy of Medicine,... Nov 2023AL amyloidosis is the most common form of systemic amyloidosis. However, the non-specific nature of presenting symptoms requires the need for a heightened clinical... (Review)
Review
AL amyloidosis is the most common form of systemic amyloidosis. However, the non-specific nature of presenting symptoms requires the need for a heightened clinical suspicion to detect unexplained manifestations in the appropriate clinical setting. Early detection and treatment are crucial as the degree of cardiac involvement emerges as a primary prognostic predictor of survival in a patient with AL amyloidosis. Following the diagnosis of AL amyloidosis with appropriate tissue biopsies, prompt treatment with a bortezomib, cyclophosphamide and dexamethasone-based first-line induction with or without daratumumab should be initiated. The goal of treatment is to achieve the best haematologic response possible, ideally with involved free light chain <20 mg/L, as it offers the best chance of organ function improvement. Treatment should be changed if patients do not achieve a partial response within 2 cycles of treatment or very good partial response after 4 cycles or after autologous stem cell transplant, as achievement of profound and prolonged clonal responses translates to better organ response and long-term outcomes. Early involvement of multidisciplinary subspecialists such as renal physicians, cardiologists, neurologists, and gastroenterologists for optimal maintenance and support of involved organs is recommended for optimal management of patients with AL amyloidosis.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Dexamethasone; Singapore; Bortezomib; Cyclophosphamide; Antineoplastic Combined Chemotherapy Protocols; Consensus; Antibodies, Monoclonal; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation
PubMed: 38920149
DOI: 10.47102/annals-acadmedsg.2023101