1.Omics Analysis of Ferroptosis and Establishment of Prognostic Model for multiple myeloma Patients.
Zi-Ning WANG ; Hao-Ran CHEN ; Jun-Dong ZHANG ; Xue-Chun LU
Journal of Experimental Hematology 2023;31(2):411-419
OBJECTIVE:
To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients.
METHODS:
Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM.
RESULTS:
36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients.
CONCLUSION
Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.
Humans
;
Multiple Myeloma
;
Ferroptosis
;
Prognosis
;
Hematopoietic System
;
Blood Coagulation
2.Correlation between Serum Interleukin-33, β2-Microglobulin Levels and DS Stage in Patients with Multiple Myeloma.
Si-Ying WANG ; Dong-Biao QIU ; Cui-Hua FAN
Journal of Experimental Hematology 2023;31(3):788-793
OBJECTIVE:
To investigate the correlation between serum interleukin-33 (IL-33), β2microglobulin (β2-MG) levels and Durie-Salmon (DS) stage in patients with multiple myeloma (MM).
METHODS:
100 MM patients admitted to the First Affiliated Hospital of Fujian Medical University from March 2019 to January 2021 were selected and divided into stage I, stage II and stage III groups according to the DS staging system. A baseline data questionnaire of patients was designed, then the relevant baseline data and laboratory test results of patients were recorded. The levels of serum IL-33 and β2-MG of all patients were detected, and the correlation between serum IL-33, β2-MG levels and DS stage of MM patients was analyzed.
RESULTS:
Among the 100 patients with MM, there were 32 cases in stage I, 39 cases in stage II and 29 cases in stage III. The levels of serum CRP and β2-MG of patients in stage III were significantly higher than those of patients in stage I and II, and the levels of serum CRP and β2-MG of patients in stage II were significantly higher than those of patients in stage I, the differences were statistically significant (P <0.05). The level of serum IL-33 of patients in stage III was significantly lower than that of patients in stage I and II, and the level of serum IL-33 of patients in stage II was significantly lower than that of patients in stage I, the differences were statistically significant (P <0.05). There was no statistical significant difference in other data between groups (P >0.05). Kendall's tau-b correlation analysis showed that the levels of serum CRP and β2-MG were positively correlated with DS stage in MM patients (r =0.534, 0.776), the level of serum IL-33 was negatively correlated with DS stage in MM patients (r =-0.759). Ordered logistic regression analysis and forest plot showed that the low level of serum IL-33 and the high level of β2-MG were the influencing factors of high DS stage in MM patients (P <0.05 ).
CONCLUSION
DS stage of MM patients is closely related to the levels of serum IL-33 and β2-MG, that is, the lower the serum IL-33 level and the higher the β2-MG level, and the higher the DS stage of MM patients.
Humans
;
Interleukin-33
;
Multiple Myeloma
;
Prognosis
;
HLA-G Antigens/blood*
3.Comparison of Plerixafor or Cyclophosphamide Combined with G-CSF in Mobilization of Peripheral Blood Stem Cells in Multiple Myeloma.
Wan-Ting LI ; Liang-Ming MA ; Yu LIAN ; Quan-Gang WANG ; Zhong-Jie GAO ; Shuang ZHAO
Journal of Experimental Hematology 2023;31(5):1403-1409
OBJECTIVE:
To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM).
METHODS:
The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34+ cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens.
RESULTS:
The 41 patients underwent 97 mobilization collections, and the median number of CD34+ cells collected was 6.09 (0-34.07)×106/kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34+ cells collected and acquisition success rate (P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34+ cell count (P <0.05). The PXF+G-CSF group had a larger number of CD34+ cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased (P <0.05).
CONCLUSION
PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34+ cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.
Humans
;
Antigens, CD34/metabolism*
;
Cyclophosphamide/therapeutic use*
;
Granulocyte Colony-Stimulating Factor/therapeutic use*
;
Hematopoietic Stem Cell Mobilization/methods*
;
Hematopoietic Stem Cell Transplantation
;
Heterocyclic Compounds/therapeutic use*
;
Multiple Myeloma/drug therapy*
;
Peripheral Blood Stem Cells/metabolism*
;
Retrospective Studies
4.Efficacy and Safety of Etoposide Combined with Cyclophosphamide for Autologous Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma.
Song-Tao TU ; Yu-Lan ZHOU ; Fei LI
Journal of Experimental Hematology 2023;31(5):1410-1414
OBJECTIVE:
To evaluate the efficacy and safety of etoposide combined with cyclophosphamide (EC) regimen for mobilization of autologous peripheral blood stem cells (APBSCs) in patients with multiple myeloma (MM).
METHODS:
The clinical data of 48 MM patients who received APBSC transplantation (APBSCT) in Department of Hematology of the First Affiliated Hospital of Nanchang University from January 2015 to October 2021 were retrospectively analyzed. The mobilization success rate and mobilization optimal rate of EC regimen were counted, and its effect on transplant efficacy, adverse reactions, hematopoietic reconstitution after transplantation, and survival time of MM patients were analyzed.
RESULTS:
APBSCs were collected on day 14 (10-19) after EC administration. The median of collected CD34+ cells was 6.82 (1.27-22.57)×106/kg, and the median number of apheresis session was 2 (1-4). The mobilization success rate (collecting CD34+ cells≥2×106 cells/kg after completion of apheresis) was 98% (47/48), and mobilization optimal rate (collecting CD34+ cells≥5×106 cells/kg after completion of apheresis) was 71% (34/48). The depth of remission were improved after APBSCT, and the complete remission (CR) rate increased from 45.8% before transplantation to 87.5% after transplantation (P <0.01). There was no transplant-related death, no blood transfusion during mobilization, and no mucositis occurred in the patients. The most common complication was neutropenia, with an incidence of 75.0% (36/48). After transplantation, all the patients successfully achieved hematopoietic reconstitution. The median time to neutrophil engraftment was 10 (9-26) days, and median time to platelet engraftment was 10 (8-33) days. By the end of follow-up, both the median progression-free survival (PFS) and overall survival (OS) time were not reached. The 5-year estimated PFS rate and OS rate was 53.8% and 82.4%, respectively.
CONCLUSION
The EC regimen for mobilization of APBSC has a high acquisition success rate and controllable adverse reactions, which can be an effective and safe mobilization regimen in MM patients.
Humans
;
Multiple Myeloma/therapy*
;
Etoposide/therapeutic use*
;
Peripheral Blood Stem Cells
;
Hematopoietic Stem Cell Mobilization/adverse effects*
;
Retrospective Studies
;
Granulocyte Colony-Stimulating Factor
;
Cyclophosphamide/therapeutic use*
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Transplantation, Autologous/adverse effects*
5.Correlation between Peripheral Blood PLR with Treg, Th17 in Newly Diagnosed Multiple Myeloma and Its Influence on Prognosis.
Na QIN ; Rui Ting FENG ; Xuan WANG ; Shu-Xia GUO
Journal of Experimental Hematology 2023;31(6):1757-1763
OBJECTIVE:
To investigate the correlation of peripheral blood platelet/lymphocyte ratio (PLR) with Treg and Th17 and its influence on prognosis in newly diagnosed multiple myeloma (MM).
METHODS:
One hundred thirty-five newly diagnosed multiple myeloma patients admitted to the Department of Hematology of Zhengzhou People's Hospital from June 2015 to October 2022 were selected as MM group. Clinical data included sex, age, immune typing, ISS stage, blood calcium (Ca), albumin (ALB), hemoglobin (Hb), PLR, LDH, β2 microglobulin (β2-MG), Treg and Th17 levels. Sixty healthy volunteers who underwent physical examination in our hospital during the same period were selected as the control group. PLR, Treg and Th17 levels in MM group and control group were compared. Pearson was used to analyze the correlation between PLR and Treg, Th17. The relationship between MM patients with different PLR and clinical features and prognosis was analyzed.
RESULTS:
The PLR and Th17 of MM patients were significantly higher than that of control group, and Treg was significantly lower than that of control group (P<0.05). In MM patients, PLR was negatively correlated with Treg (r=-0.616), and PLR was positively correlated with Th17 (r=0.555). Using mean PLR=132.72 as the boundary, 135 MM patients were divided into high PLR group (n=54) and low PLR group (n=81). In MM patients with high PLR, ISS stage, ALB and Treg were significantly higher than those in low PLR group, while Th17 was significantly lower than those in low PLR group (P<0.05). By univariate and COX regression analysis, PLR was an independent prognostic risk factor for newly diagnosed MM patients (P<0.05). MM patients with high PLR had better PFS and OS, and the difference was statistically significant compared with MM patients with low PLR (P<0.05). 65 patients admitted from June 2015 to December 2018 were used as the training set, and 70 patients admitted from January 2019 to October 2022 were used as the validation set. The OS of MM patients with different PLR were compared respectively. The results showed that the conclusions of the training set and the validation set were consistent. PLR with high expression had higher OS (P<0.01).
CONCLUSION
PLR is correlated with Treg and Th17 in newly diagnosed MM patients, and high PLR has better prognosis. PLR can be used to evaluate the prognosis of MM patients.
Humans
;
Multiple Myeloma/diagnosis*
;
Blood Platelets
;
T-Lymphocytes, Regulatory
;
Prognosis
;
Th17 Cells
;
Retrospective Studies
6.The Value of Serum HMGB1 and sRAGE in the Diagnosis, Efficacy Monitoring and Prognosis of Newly Diagnosed Multiple Myeloma.
Juan WANG ; Ai-Ming ZENG ; Shu-Fen LIANG
Journal of Experimental Hematology 2022;30(2):493-500
OBJECTIVE:
To evaluate the value of high mobility group protein B1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the diagnosis, efficacy monitoring and prognosis of newly diagnosed multiple myeloma (MM) patients.
METHODS:
Fifty newly diagnosed MM patients before and after chemotherapy and 50 hematological outpatients from October 2018 to May 2020 were selected. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 and sRAGE levels of the patients. ROC was used to further analyze the efficacy of serum HMGB1 and sRAGE levels on the diagnosis of MM. At the same time, the serum levels of HMGB1 and sRAGE before and after chemotherapy were compared, and their values in the evaluation of curative effect of MM patients were analyzed. According to the mean values of serum HMGB1 and sRAGE, all the patients were divided into different groups, the clinical characteristics and survival status of the patients were compared.
RESULTS:
Before treatment the serum HMGB1 level of the patients in MM group was higher than that in control group, while sRAGE level was lower (t=11.363,6.127, P<0.001). The AUC of serum HMGB1 and sRAGE in the MM patients was 0.955 and 0.811, respectively. After 3 courses of chemotherapy, HMGB1 level of the patients in CR group was lower than before chemotherapy, while in PD group was higher, as well as sRAGE level of the patients in PR group (P<0.05). There were significant differences in R-ISS stage, HGB, CRP, ESR, CD56, CD117, D13S319 deletion between HMGB1 high expression group and HMGB1 low expression group (χ2=3.920, 6.522, 6.65, 4.16, 3.945, 6.65, 4.16, P<0.05), while there were significant differences in ISS stage, CRP and CD56 between sRAGE low expression group (28 cases) and sRAGE high expression group (22 cases) (χ2=4.565, 4.711, 5.547, P<0.05). Kaplan-Meier survival analysis showed that the patients in HMGB1 low expression group had better survival condition, for PFS Tlow>Thigh (χ2=9.470, P<0.05), and for OS Tlow>Thigh (χ2=7.808, P<0.05); there was no difference in the survival of sRAGE high expression group and low expression group, for PFS Tlow
Enzyme-Linked Immunosorbent Assay
;
HMGB1 Protein/blood*
;
Humans
;
Multiple Myeloma/therapy*
;
Prognosis
;
Receptor for Advanced Glycation End Products/blood*
7.Correlation between Serum Free Light Chain and Blood Routine Parameters in Patients with Multiple Myeloma.
Dan LI ; Nan JIANG ; Jia-Qiang WANG ; Zhi-Bin WANG ; Yuan HE ; Juan ZHANG
Journal of Experimental Hematology 2022;30(5):1446-1452
OBJECTIVE:
To investigate the correlation between serum free light chain (sFLC) and blood routine parameters in patients with multiple myeloma (MM).
METHODS:
347 patients with multiple myeloma diagnosed in Sichuan people's Hospital from April 2019 to July 2021 were selected. sFLC, serum total light chain (sTLC), peripheral blood routine, coagulation and biochemical parameters were analyzed retrospectively. The correlation analysis between sFLC and blood routine parameters were calculated by Pearson or Spearman correlation coefficients. Multiple stepwise linear regression was used to screen the combined blood routine parameters related to sFLC. The efficacy of the selected blood routine parameters eflecting sFLC level was evaluated, the Kruskal Wallis test of independent samples was used for inter group comparison, and the receiver operating characteristic (ROC) curve was drawn at the same time.
RESULTS:
In MM patients, sFLC was positively related with sTLCκ, sTLCλ, sTLCκ/λ, Cr, Urea, Cr and Cys_C significantly, while negatively correlated with eGFR markedly (|r|≥0.3). Multivariate stepwise linear regression showed that the influence factors of sFLCκ were Cr and sTLCκ (P=0.000, P=0.003), the influence factors of sFLCλ were eGFR and sTLCλ(P=0.000, P=0.000), the sFLCκ/λ influence factor was sTLCκ/λ (P=0.032). Kruskal Wallis test of independent samples showed that Cr and sTLCκ, eGFR and sTLCλ, TLCκ/λ were good or better parameters to reflect the level of sFLCκ, sFLCλ and sFLCκ/λ in MM patients(P<0.05), respectively. ROC curve analysis shows that Cr, sTLCκ, eGFR, sTLCλ and sTLCκ/λ had the ability to judge the abnormality of sFLC in MM patients (AUC=0.684-0.875, P<0.05).
CONCLUSION
In MM patients, sTLCκ and sTLCλ with renal function parameters could evaluate sFLCκ or sFLCλ level respectively, while sFLC κ/λ was estimated by sTLCκ/λ.
Blood Coagulation Tests
;
Humans
;
Immunoglobulin Light Chains
;
Multiple Myeloma
;
Retrospective Studies
;
Urea
8.Value of Neutrophil/Lymphocyte Ratio and Monocyte/Lymphocyte Ratio in the Prognosis of Patients with Multiple Myeloma.
Wen-Hui YANG ; Yan-Qing SUN ; Qi-Ke ZHANG ; Xiao-Fang WEI ; Gao LI
Journal of Experimental Hematology 2021;29(1):122-130
OBJECTIVE:
To investigate the effect of neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR) in the valuation prognosis of patients with multiple myeloma (MM).
METHODS:
The clinical data of 82 patients with initially diagnosed MM admitted to Gansu Provincial People's Hospital was analyzed retrospectively. NLR and MLR were calculated based on blood routine results respectively. The optimal cut-off point of NLR and MLR was determined according to the ROC curve, and the patients were divided into the high NLR/MLR group and the low NLR/MLR group. The general data, biochemical indicators and prognosis of the patients in each groups were compared respectively. The prognostic significance of the high NLR/MLR group and the low NLR/MLR group in patients between different treatment regimens and different clinical characteristics were analyzed. Risk stratification was designed based on NLR and high MLR as two risk factors, and the effect of risk factors, on the prognosis of MM patients were compared.
RESULTS:
ROC curve analysis determined that the optimal cut-off point of NLR was 3.1 (sensitivity 75%, specificity 70.7%) and the optimal cut-off point of MLR was 0.34 (sensitivity 83.3%, specificity 53.4%). The lactate dehydrogenase (LDH) and mean platelet volume (MPV) were correlated to NLR and MLR (P<0.05). There were no significant difference in age, sex, serum calcium (Ca), β
CONCLUSION
Elevated NLR and MLR are associated with poor prognosis in MM patients and may serve as the cost-effective and readily available prognostic biomarkers.
Blood Platelets
;
Humans
;
Lymphocytes
;
Monocytes
;
Multiple Myeloma
;
Neutrophils
;
Prognosis
;
Retrospective Studies
9.Coagulation Indexes and Their Prognostic Significance in Patients with Multiple Myeloma.
Qing-Fen LI ; Qi-Ke ZHANG ; Xiao-Fang WEI ; You-Fan FENG
Journal of Experimental Hematology 2021;29(3):791-796
OBJECTIVE:
To analyze the relationship between coagulation indexes and prognosis of patients with multiple myeloma (MM).
METHODS:
A total of 99 newly diagnosed MM patients treated in Gansu Provincial Hospital from October 2017 to October 2019 were enrolled. Plasma thromboplastin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (D-D), platelet (PLT), and other laboratory indexes were detected. The relationship between coagulation indexes and clinical characteristics of MM patients was analyzed. The differences in survival rates among MM patients with different levels of coagulation indexes were compared, and the effect of each clinical index on the prognosis of MM patients was analyzed by univariate and multivariate.
RESULTS:
Each coagulation index was correlated to sex, disease classification and stage, and β
CONCLUSION
Coagulation function is correlated with multiple clinical indicators of patients with MM and plays an important role in their prognosis.
Blood Coagulation Tests
;
Fibrin Fibrinogen Degradation Products
;
Humans
;
Multiple Myeloma
;
Partial Thromboplastin Time
;
Platelet Count
;
Prognosis
;
Prothrombin Time
10.Analysis of Factors Influencing Autologous Peripheral Blood Stem Cells Mobilization in Patients with Lymphoma and Multiple Myeloma.
Yong-Feng SU ; Yi-Zhi WANG ; Hong-Mei NING ; Liang-Ding HU
Journal of Experimental Hematology 2021;29(6):1945-1949
OBJECTIVE:
To analyze the factors influencing the mobilization of autologous peripheral blood stem cells (auto-PBSCs) in patients with lymphoma and multiple myeloma, and provide reference for optimizing the autologous stem cell mobilization regimen.
METHODS:
Clinical data of 33 multiple myeloma and lymphoma patients received auto-PBSCs mobilization in our center from January 2015 to December 2018 were collected, the correlation of mobilization failure rate with gender, age, courses of chemotherapy before mobilization, does of recombinant human granulocyte colony stimulating factor (rhG-CSF), type of disease, and chemotherapy regimen were retrospectively analyzed.
RESULTS:
Type of disease and course of pre-mobilization chemotherapy could affect the mobilization failure rate (P<0.05). The mobilization failure rate of lymphoma patients was 42.1%, which was significantly higher than 7.1% of multiple myeloma patients (P=0.026). The mobilization failure rate was higher in the group with chemotherapy courses≥5 before mobilization (P=0.016). Age, gender, dose of rhG-CSF, and chemotherapy regimen had no significant correlation with mobilization failure rate (P>0.05).
CONCLUSION
Multi-course chemotherapy before collection and lymphoma patients are poor factors negatively impacting on auto-PBSCs mobilization.
Hematopoietic Stem Cell Mobilization
;
Humans
;
Lymphoma/therapy*
;
Multiple Myeloma/therapy*
;
Peripheral Blood Stem Cells
;
Retrospective Studies

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