1.Construction and preliminary verification of a nomogram for survival of TKI-treated adult patients with newly diagnosed chronic myelogenous leukemia in the chronic phase
Guangling HU ; Haiping LIANG ; Xuehan MA ; Bei LIU
Journal of Leukemia & Lymphoma 2025;34(1):16-23
Objective:To investigate the related factors affecting the survival of adult patients with newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP) treated with tyrosine kinase inhibitor (TKI) and the prognostic predictive effect of the nomogram constructed according to them.Methods:A retrospective cohort study was conducted. Clinical general information and laboratory index data of 243 newly diagnosed adult CML-CP patients treated with TKI in the First Hospital of Lanzhou University from December 2008 to June 2023 were collected, and they were divided into a training set (194 patients) and a validation set (49 patients) by complete randomization in the ratio of 8∶2. In the training set, variables affecting poor overall survival (OS) of patients were analyzed using univariate and multivariate Cox proportional hazards models by R4.3.2 software to obtain the independent influences of poor OS, on the basis of which the Cox regression model was constructed and the nomogram predicting the OS rate at 8 and 10 years was plotted. Kaplan-Meier method was applied to analyze the OS in all 243 patients and patients stratified by the screened independent influencing factors for poor OS, and log-rank test was used for comparison between the groups. In the training and validation sets, receiver operating characteristic (ROC) curve was used to analyze the effect of the nomogram on predicting 8- and 10-year OS rates of patients with actual survival as the gold standard; calibration curve was used to assess the accuracy of predictions of the nomogram; decision curve analysis (DCA) was used to assess the clinical utility of the nomogram.Results:The median age of 243 CML-CP patients [ M ( Q1, Q3)] was 46 (35, 58) years old, 150 cases (61.7%) were male and 9 cases (38.3%) were female, 119 cases (49.0%) had comorbidities, and the efficacy of 82 cases (33.7%) reached molecular response (MR) 5.0. Differences in patient compositions for age and gender, levels of major indicators for peripheral blood and bone marrow, spleen size, comorbidities, short-term efficacy, Sokal score, and long-term survival score of European Treatment and Outcomes Study between the training and validation sets were not statistically significant (all P > 0.05). Multivariate Cox regression analysis showed that patients with elevated age ( HR = 1.04, 95% CI: 1.01-1.08, P = 0.041), comorbidities (with vs. without, HR = 3.48, 95% CI: 1.23-9.86, P = 0.019), and those who did not achieve MR5.0 (achieved vs. unachieved, HR = 0.13, 95% CI: 0.02-0.97, P = 0.046) were independent risk factors for poor OS in TKI-treated newly diagnosed adult CML-CP patients. By the last follow-up (December 2023), the median follow-up was 72 months, with the range of 6-180 months. Kaplan-Meier method analysis showed that the 8- and 10-year OS rates of 243 patients were 83.7% and 81.6%, respectively; patients with age ≥46 years compared to <46 years, with comorbidities compared to without comorbidities, and who did not achieve MR5.0 in terms of efficacy compared to who achieved MR5.0, the OS was poorer, and the differences were statistically significant (all P < 0.01). The nomogram of 8- and 10-year OS rates in TKI-treated newly diagnosed adult CML-CP patients was constructed based on the screened independent influencing factors of poor OS. The area under the ROC curve was 0.910 and 0.851 in the training set and 0.778 and 0.764 in the validation set for the predicted 8- and 10-year OS rates based on the nomogram, respectively, and the calibration curve showed that the predicted 8- and 10-year OS rates based on the nomogram were in high agreement with the actual ones in the training and validation sets; the DCA showed that the nomogram within a certain prediction threshold could benefit the clinical decision-making in both the training and validation sets. Conclusions:Having comorbidities, not reaching MR5.0 in efficacy and old age are independent risk factors for poor survival of TKI-treated adult patients with newly diagnosed CML-CP, and the nomogram constructed based on these 3 factors has a good predictive ability for the survival of such patients.
2.Clinical characteristics and prognosis analysis of pediatric acute lymphoblastic leukemia with hyperleukocytosis
Wenqi LU ; Zhangyue WEI ; Lin WAN
Journal of Leukemia & Lymphoma 2025;34(1):24-29
Objective:To explore the clinical characteristics and prognosis of pediatric acute lymphoblastic leukemia with hyperleukocytosis (HL-ALL).Methods:A retrospective case series study was conducted. Clinical data of 153 children with initial diagnosis of HL-ALL from January 2016 to April 2023 in Children's Hospital of Soochow University were retrospectively analyzed. The clinical characteristics, cytogenetic and molecular biological features, immunophenotyping, treatment response and prognosis of the children were recorded. The children were divided into B-lineage and T-lineage groups according to immunophenotyping; the clinical characteristics of the two groups were compared; the overall survival (OS) of children in the two groups was analyzed by the Kaplan-Meier method, and the log-rank test was performed; the factors affecting OS were analyzed by using the Cox proportional hazards model.Results:Among the 153 children, 105 cases were detected with disease-related fusion genes, including 31 cases of Philadelphia chromosome-positive (Ph +)/Philadelphia chromosome-like (Ph-like). Tumor lysis syndrome (TLS) was present during induction therapy in 28 cases, pulmonary infection in 53 cases, intracranial hemorrhage in 6 cases, and sepsis in 12 cases. Immunophenotyping showed 86 cases were lineage B and 67 cases were lineage T. There were statistically significant differences in gender and age of the children between the B-lineage and T-lineage groups (both P < 0.05); the incidence of coagulation abnormalities and the levels of hemoglobin, lactate dehydrogenase and uric acid in the B-lineage group were lower than those in the T-lineage group (all P < 0.001). The positive rates of Ph +/Ph-like, MLL rearrangement, E2A-PBX1 and TEL-AML in the B-lineage group were higher than those in the T-lineage group (all P < 0.05), while the positive rates of SIL-TAL was lower than that in the T-lineage group ( P < 0.05). In terms of early complications, the incidence of TLS in the B-lineage group was lower than that in the T-lineage group ( P < 0.05). The median follow-up time [ M ( Q1, Q3)] was 1 150 (460-2 000) d until 30 April 2024, and the 3-year OS rates of children in the B-lineage and T-lineage groups were 80.6% and 67.1%, respectively; the difference in OS of children between the two groups was not statistically significant ( P = 0.168). The results of univariate Cox analysis showed that white blood cell count, Ph +/Ph-like positivity, occurrence of TLS, pulmonary infection, and intracranial hemorrhage were the influencing factors of OS in B-lineage HL-ALL children (all P < 0.05); white blood cell count and coagulation abnormalities were the influencing factors of OS in T-lineage HL-ALL children (both P < 0.05). Conclusions:There are differences in children's gender, age, laboratory parameters and genetics between the B-lineage and T-lineage groups in HL-ALL. White blood cell count, Ph +/Ph-like positivity, occurrence of TLS, pulmonary infection, and intracranial hemorrhage are the factors affecting OS of B-lineage HL-ALL children; white blood cell count and coagulation abnormalities are the factors affecting OS of T-lineage HL-ALL children.
3.Clinical characteristics and prognosis analysis of T-lymphoblastic lymphoma
Xiyu LI ; Min ZHANG ; Jingjing ZHANG ; Chunyan YANG ; Qian HUANG ; Haiyan WANG ; Lu JIA ; Lulu CHEN ; Hao ZHANG
Journal of Leukemia & Lymphoma 2025;34(1):30-33
Objective:To investigate the clinical characteristics and prognosis of T-lymphoblastic lymphoma (T-LBL).Methods:A retrospective case series study was conducted. Clinical data of patients diagnosed with T-LBL at the Affiliated Hospital of Jining Medical University from January 2013 to March 2023 were retrospectively analyzed, and their clinical characteristics and prognosis were statistically analyzed.Results:A total of 22 T-LBL patients were included. Among them, there were 19 males (86.4%) and 3 females (13.6%), and the median age at onset was 19.5 (15, 28) years old. Based on Ann Arbor staging, 3 cases (13.6%) were classified as stage Ⅰ-Ⅱ, while 19 cases (86.4%) were stage Ⅲ-Ⅳ; 10 cases (45.5%) presented with B symptoms, 12 cases (54.5%) without B symptoms; 16 cases (72.7%) showed elevated lactic dehydrogenase (LDH) level. At onset, 7 patients (31.8%) had mediastinal masses, 3 patients (13.6%) had central nervous system involvement, and 17 patients (77.3%) had bone marrow involvement. The overall response rate (ORR) and complete remission rate among the 22 patients were 81.82% (18/22) and 31.82% (7/22), respectively. The ORR was 84.21% (16/19) in 19 patients treated with ALL-like regimens. Among 3 patients treated with NHL-like regimens, 1 case achieved complete remission and 1 case achieved partial remission. Seven patients received allogeneic hematopoietic stem cell transplantation, with a median overall survival (OS) time of 22 months; the median OS time of patients without allogeneic hematopoietic stem cell transplantation was 14 months. The 3-year OS rates in the allogeneic hematopoietic stem cell transplantation group and group without allogeneic hematopoietic stem cell transplantation were 64.30% and 16.00%, and the difference in OS between the two groups was statistically significant ( P = 0.043). Two patients with disease progression prior to transplantation died of multidrug-resistant bacterial infections after transplantation. Conclusions:T-LBL is rare, and it is a highly aggressive tumor that predominantly occurs in adolescent males. Allogeneic hematopoietic stem cell transplantation can prolong OS, reduce relapse and improve the prognosis of patients.
4.Relationship between acute leukemia and blood lipid level: a Meta-analysis
Yan LIANG ; Mengying CUI ; Shaojuan DONG ; Danxia ZHU ; Ying BAO ; Jian CUI
Journal of Leukemia & Lymphoma 2025;34(1):34-39
Objective:To explore the relationship between acute leukemia and blood lipid level.Methods:The Chinese and English literature on the relationship between acute leukemia and blood lipid level published in PubMed, Web of Science, Cochrane library, CNKI, Wanfang, and VIP databases from the establishment of the database to December 2023 was searched, the literature that met the evaluation criteria was screened, and the quality of the literature was evaluated by using the Newcastle-Ottawa scale. Basic clinical characteristics and blood lipid-related data were obtained from the acute leukemia patients (acute leukemia group) and the healthy individuals who underwent physical examination or patients with non-hematological disorders that did not lead to abnormal blood lipid metabolism and who did not take medications that affected blood lipid during the same period (control group). Meta-analysis of the differences in peripheral blood levels of total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) between the two groups was carried out by using Stata 14.0 software to make forest plots and to calculate the combined weighted mean difference (WMD) or standardised mean difference (SMD) and 95% CI. Results:Six articles were finally included, published between 2005 and 2023, all of which were of moderate quality. Finally, 558 patients with acute leukemia and 323 controls were included in the analysis. By Meta-analysis, TG level in the acute leukemia group was higher than that in the control group (WMD = 0.30, 95% CI: 0.07-0.54, P = 0.012), HDL-c (SMD = -1.54, 95% CI: -2.11--0.97, P < 0.001) and LDL-c (WMD = -0.57, 95% CI: -0.72 - -0.41, P < 0.001) levels were lower than those in the control group, and the differences were all statistically significant; the difference in TC between the acute leukemia group and the control group was not statistically significant (WMD = -0.34, 95% CI: -0.82-0.13, P = 0.157). Conclusions:Compared with normal subjects, patients with acute leukemia have high TG level and low LDL-c and HDL-c levels.
5.Progress of propylene glycol-free melphalan hydrochloride for injection in hematologic malignancies
Journal of Leukemia & Lymphoma 2025;34(1):54-57
Mephalan is a classic nitrogen mustard alkylating agent, and its intravenous formulation is used in the treatment of various hematologic malignancies. In 2018, propylene glycol-free melphalan hydrochloride for injection (PGF-Mel) which uses a novel cyclodextrin encapsulation technology was approved for marketing in China, and it has better solubility and stability after reconstitution than propylene glycol-solubilized melphalan (e.g., Alkeran injection). This article reviews the basic pharmacological properties, systemic drug exposure and efficacy and safety of PGF-Mel in different hematologic malignancies.
6.Recommendations for infection prevention in multiple myeloma
Journal of Leukemia & Lymphoma 2025;34(1):57-61
Infection remains the leading cause of morbidity and mortality in patients with multiple myeloma (MM) because of the cumulative effect of disease, treatment and host-related factors. This article conducts a comprehensive review of the existing literature and current guidelines, addressing issues pertaining to infection risk and prevention of infectious complications in MM in the context of new therapeutics. Additionally, it provides suggestions for effectively preventing these complications in MM. Optimal prevention strategies encompass vaccination against common pathogens, antibiotic prophylaxis, implementation of infection control measures, as well as immunoglobulin substitution for a small subset of patients.
7.Progress of chimeric antigen receptor T-cell therapy for malignant tumors
Journal of Leukemia & Lymphoma 2025;34(1):61-64
Chimeric antigen receptor T (CAR-T) cell immunotherapy is a new type of precision-targeted therapy, which can be used to modify the patient's own T cells to make them have stronger anti-tumor activity, and has achieved good results in treatment of hematologic neoplasms in recent years. Exploring the application of CAR-T cell immunotherapy in solid tumors has also been a hot research topic in recent years. The article reviews the research progress of CAR-T cell therapy for malignant tumors to provide reference for clinical application.
8.Expression of OLFML2A in acute leukemia patients and its diagnostic and prognostic evaluation value
Yao HE ; Jinlian LI ; Xuan LU ; Wanchuan ZHUANG ; Xingxing CHAI
Journal of Leukemia & Lymphoma 2025;34(2):73-79
Objective:To investigate the transcriptional level expression of olfactomedin-like protein 2A (OLFML2A) in peripheral blood of patients with acute leukemia (AL) and its diagnostic and prognostic evaluation value.Methods:A retrospective cohort study was conducted. A total of 34 patients with AL (AL group) admitted to the Second People's Hospital of Lianyungang from January 2019 to March 2023 were selected, including 26 cases of acute myeloid leukemia (AML) (non-acute promyelocytic leukemia) and 8 cases of acute lymphoblastic leukemia (ALL). Another 15 healthy subjects who underwent the physical examination during the same period were selected as the healthy control group. Among 26 patients with AML, 18 were males and 8 were females. The median age [ M (IQR)] was 59 (9) years; 5 cases relapsed. Among 8 patients with ALL, 4 were males and 4 were females. The median age was 48 (12) years; 1 case relapsed. Real-time fluorescence quantitative polymerase chain reaction (qPCR) medthod was used to detect the relative expression level of OLFML2A mRNA in peripheral blood of each group. The relative expression levels of OLFML2A mRNA among the different patients stratified by clinicopathological factors were compared. Taking bone marrow smear cytology or bone marrow biopsy as the gold standard, receiver operating characteristic (ROC) curve was used to analyze the diagnostic effect of the relative expression level of OLFML2A mRNA on AML and ALL. According to the median relative expression level of OLFML2A mRNA in AL patients, the patients were divided into the high expression of OLFML2A mRNA (≥ the median) and the low expression of OLFML2A mRNA (< the median) groups. Progression-free survival (PFS) and overall survival (OS) of both groups were analyzed by using Kaplan-Meier curve. The log-rank test was used for comparison between groups. Results:The median relative expression level of OLFML2A mRNA in AL group was higher than that in the healthy control group [3.53 (8.19) vs. 0.27 (0.23)], and the difference was statistically significant ( Z = 4.38, P < 0.001). The median relative expression level of OLFML2A mRNA in AML group was higher than that in ALL group [4.92, (9.80) vs. 1.60 (4.35)], which were higher than that in the healthy control group; and the differences were statistically significant (all P < 0.05). There were statistically significant differences in the relative expression level of OLFML2A mRNA among AML patients with different prognosis risk stratification, fusion gene positive or not, whether there was chromosome abnormality, and whether the average daily hospitalization cost was < 2 500 yuan (all P < 0.05). There were statistically significant differences in the relative expression level of OLFML2A mRNA among ALL patients with different prognostic risk stratification, whether there was fusion gene and whether there was chromosome abnormality (all P < 0.05). ROC curve analysis showed that the area under the curve for the diagnosis of AML based on the relative expression level of OLFML2A mRNA was 0.936 (95% CI: 0.862-1.000), and the optimal cut-off value was 0.780; the area under the curve for the diagnosis ALL was 0.767 (95% CI: 0.535-0.998), and the optimal cut-off value was 0.558. Kaplan-Meier survival curve analysis showed that the 3-year PSF rate in AL patients with high expression of OLFML2A mRNA (17 cases) and low expression of OLFML2A mRNA was 20.5% and 30.6%, respectively, and PFS in AL patients with low expression of OLFML2A mRNA was superior to those with high expression, and the difference was statistically significant ( χ2 = 4.64, P = 0.031). The 3-year OS rates in AL patients with high and low expression of OLFML2A mRNA was 40.4% and 33.3%, respectively, and there was no statistically significant difference in OS between the 2 groups ( χ2 = 1.55, P = 0.213). Conclusions:The relative expression level of OLFML2A mRNA is high in AL patients, and it is more significant in AML patients. The level of OLFML2A gene has a certain value in the diagnostic and prognostic evaluation of AL.
9.Diagnostic value of plasma IL-2, IL-6 and IFN-γ in non-Hodgkin lymphoma
Qiong WU ; Liping KONG ; Yuan DONG ; Li LI ; Siyu ZONG ; Jinge XU ; Qingyun WU
Journal of Leukemia & Lymphoma 2025;34(2):80-84
Objective:To investigate the diagnostic value of plasma cytokines such as interleukin (IL)-2, IL-6 and interferon (IFN)-γ in non-Hodgkin lymphoma (NHL).Methods:A retrospective case-control study was conducted. A total of 48 NHL patients admitted to the Second Affiliated Hospital of Xuzhou Medical University between January 2020 and December 2022 were selected as NHL group, and another 34 healthy people who underwent physical examimation during the same period were selected as the healthy control group. The levels of IL-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF) - α and IFN-γ in the plasma of patients at first admission and healthy subjects during physical examination were detected by using flow cytometry. The differences in general data and all cytokines levels of both groups were compared. The collinearity stepwise screening was made in 7 cytokines levels, and the screened variables were included in multivariate binary logistic regression model. Plasma cytokines with independent effects on the pathogenesis of NHL were screened. Taking local biopsy, histopathological examination or immunohistochemical examination as the gold standard, the receiver operating characteristic (ROC) curves of individual and combined diagnosis of NHL based on the selected cytokines were drawn to judge the diagnostic effect of all indicators on NHL.Results:There were 32 males (66.7%) and 16 females (33.3%) in NHL group, with the median age [ M ( Q1, Q3)] of 56.50 (45.75, 67.50) years; there were 28 males (82.4%) and 6 females (17.6%) in the healthy control group, with the median age of 52.00 (47.50, 55.50) years. There were no statistically significant differences in age and gender composition between the 2 groups (all P > 0.05). The levels of IL-2 [1.44 (1.36, 1.85) pg/ml vs. 1.19 (0.86, 1.68) pg/ml] and TNF-α [3.46 (2.68, 4.06) pg/ml vs. 2.23 (1.52, 3.46) pg/ml] in NHL group were higher than those in the healthy control group, and the differences were statistically significant (all P < 0.05). There were no statistically significant differences in IL-4, IL-6, IL-10, IL-17, IFN-γ levels (all P > 0.05). According to collinear stepwise screening of independent variables, IL-4 and TNF-α were excluded from 7 cytokines, and the other 5 cytokines were included in multivariate logistic regression model, and the result showed that the decreased level of IL-2 ( OR = 0.20, 95% CI: 0.08-0.53, P = 0.001) and the increased levels of IL-6 ( OR = 1.18, 95% CI: 1.04-1.33, P = 0.009) and IFN-γ ( OR = 1.26, 95% CI: 1.08-1.46, P = 0.003) were independent risk factors for the onset of NHL. The results showed that the area under the curve of IL-2, IL-6, IFN-γ and the combination of 3 indexes for the diagnosis of NHL was 0.760 (95% CI: 0.651-0.870), 0.595 (95% CI: 0.468-0.722), 0.508 (95% CI: 0.373-0.642), 0.847 (95% CI: 0.763-0.930), and the optimal cut-off value of the combination of 3 indexes was 0.730 which was calculated by logistic regression model formula; the corresponding sensitivity and specificity were 70.2% and 94.1%, respectively. Conclusions:The decreased level of IL-2 and increased levels of IL-6 and IFN-γ at initial diagnosis are risk factors for the onset of NHL. The combined detection of the 3 indexes shows a good value in the diagnosis of NHL.
10.Causal relationship between non-Hodgkin lymphoma and chronic hepatitis B virus infection: a two-sample bidirectional Mendelian randomization analysis
Liangliang DONG ; Yongjian HUANG ; Jianqiang YE ; Zilin NIAN ; Lin YANG ; Ting CHEN ; Wenbin LIU ; Qiuling ZHAO ; Juming CHEN ; Lijun LAI ; Qin CHEN
Journal of Leukemia & Lymphoma 2025;34(2):85-91
Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

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