ABSTRACT
Objective:To observe and analyze the morphological characteristic of bone marrow and peripheral blood in patients diagnosed with de novo acute leukemia.Methods:From October 1, 2015 to December 31, 2021, 1151 patients aged 47 (26, 62) years, consisting of 602 males and 549 females with newly diagnosed acute leukemia in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, were collected to preform the morphological analysis in bone marrow and peripheral blood smears. Based on the comprehensive diagnosis results of morphology, immunology, cytogenetics, and molecular biology, comparison between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), AML with RUNX1-RUNXITI gene, AML with CBFβ/MYH11 gene, acute promyelocytic leukemia (APL) with PML/RARA gene, AML with NPM1 gene, the rest of the AML, Ph+ALL and Ph-ALL were performed by Chi-square test along with analysis of the differences in the ratio of wood bundle cells, pseudo-Chediak-Higashi (PCH) inclusions, cytoplasmic small particles, nuclear notches, leukemia cells with cup-like changes (cup cells); as well as the differences in the micromeganuclei, early immature granulocytes, plasma cells, high eosinophils and other accompanying cells and the distribution of "grape-like" aggregation. Finally, the morphological characteristics of acute leukemia cells, the appearance and arrangement of accompanying cells were summarized.Results:Between AML and ALL, there were statistically significant differences in cytoplasmic Auer bodies[(45.5%, 0%), χ 2=211.400, P<0.01], PCH inclusion bodies[(28.9%, 0%), χ 2=114.100, P<0.01], cytoplasmic fine particles[(20.7%, 2.9%), χ 2=53.798, P<0.01], nuclear notches[(0.7%, 6.1%), χ 2=30.906, P<0.01], and goblet cells[(4.9%, 0.3%), χ 2=13.495, P<0.01], micromegakaryus [(22.4%, 0.3%), χ 2=80.398, P<0.01], plasma cells[(87.6%, 10.6%), χ 2=604.241, P<0.01], hyperacidophils[(15.3%, 1.0%), χ 2=46.116, P<0.01] showed significant differences in the "grape-like" aggregation distribution. In AML with RUNX1-RUNXITI gene, the changes of vacuoles and PCH inclusion bodies are more obvious; in AML with CBFβ/MYH11 gene, the increase of hypereosinophils is more obvious; in APL with PML/RARA gene, the increase of woodbundle is more obvious. The morphology of nuclei chromatin, nucleolus, and vacuoles were also different among the groups. Comparison between Ph+ALL and Ph-ALL showed that Ph+ALL was more prone to develop early immature granulocytes and plasma cells (all P<0.05). Conclusion:There are significant differences between AML and ALL in the characteristics of leukemia cells, the regularity of accompanying cells, and the aggregation and distribution patterns. The subtypes of AML with specific genetic abnormalities have their own characteristics in the appearance of vacuoles, PCH inclusions, hypereosinophils, woodbundle cells, and goblet cells. Ph+ALL is more prone to present early immature granulocytes and plasma cells.
ABSTRACT
Objective:To investigate the clinical characteristics, efficacy and prognostic influencing factors of IgD multiple myeloma (MM) in the new immunotherapy era.Methods:The clinical data of 29 patients diagnosed with IgD MM in the Affiliated Hospital of Xuzhou Medical University from March 2014 to February 2021 were retrospectively collected. The clinical characteristics, treatment regimens and efficacy, especially the efficacy of new drugs and immunotherapy for the disease were analyzed. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS). Multivariate Cox proportional risk model was used for analysis of prognostic influencing factors.Results:The median age of patients was 58 years. There were 20 cases (69.0%) below 65 years, 12 cases (41.4%) of complicated with stomach function damage, 6 cases (20.7%) of extramedullary invasion. All patients were treated with combined therapy containing proteasome inhibitor bortezomib in the first-line therapy, and the overall response rate was 82.8% (24/29). Among 21 relapsed/refractory patients, 12 patients were treated with the second-line or above treatment regimen chimeric antigen receptor T cell (CAR-T) immunotherapy, including 9 cases achieving very good partial remission (VGPR) or above; 5 patients were treated with the new drug daratozumab, including 1 case achieving complete remission (CR). The median OS time of 29 patients was 48 months (95% CI 17-79 months), the median PFS time after the first-line treatment was 9 months (95% CI 3-15 months), and the median PFS time after the second-line treatment was 11 months (95% CI 1-21 months). Multivariate Cox regression results showed that CAR-T therapy is an independent influencing factor of the prognosis of relapsed/ refractory IgD MM patients ( HR = 0.094, 95% CI 0.019-0.473, P = 0.004). Conclusions:IgD MM patients are characterized with lower onset age, more renal function damage and a high incidence of extramedullary invasion. The first-line therapy containing proteasome inhibitor has a better short-term efficacy, and CAR-T therapy can improve the remission rate and survival rate of relapsed/refractory IgD MM to a certain extent.
ABSTRACT
Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.
ABSTRACT
Objective:To explore an assay that can concisely, rapidly, and accurately quantify the amount of chimeric antigen receptor (CAR)-T cells in the bone marrow or peripheral blood of patients after CAR-T cell immunotherapy by morphological analysis and flow cytometry assay, providing timely and accurate feedback for clinical treatment.Methods:We analyzed the CAR-T cell detection results in peripheral blood and bone marrow of 256 patients who received CAR-T cell immunotherapy in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University from August 2016 to August 2021. All 256 patients survived more than one month after CAR-T cell infusion. Among them, there were 118 patients with multiple myeloma, 68 patients with acute lymphoblastic leukemia, and 70 patients with lymphoma. The morphological characteristics, positive rate and detection rate of CAR-T cell in peripheral blood and bone marrow were analyzed by morphological methods. The positive rate and detection rate of CAR-T in peripheral blood and bone marrow were analyzed by flow cytometry protein L detection. χ 2 test was used to comprehensively analyze the difference between the detection rate of the combined analysis of the two methods and the detection rate of the single method. Results:CAR-T cells have significant morphological characteristics, and there are obvious morphological differences from normal lymphocytes. The detection rates of CAR-T cells in peripheral blood or bone marrow by morphological methods and flow cytometry were 88.28%(226/256) and 79.29% (203/256), respectively. When the two methods were combined, the detection rate of CAR-T cells can reach 99.22%, with statistically significant difference comparing to that of single method( P<0.05). Through the analysis of the detection results of peripheral blood at different time points, it was found that the average detection rates of morphology and flow cytometry in 118 patients with multiple myeloma were 9.50% and 10.23% on the 7th day, and 13.50% and 15.19% respectively on the 15th day. On the 21st day, the average detection rates of morphology and flow cytometry were 8.00% and 10.07%, respectively. The average detection rates of morphology and flow cytometry in 68 patients with acute lymphoblastic leukemia were 12.00% and 11.22% on the 7th day, and 21.00% and 23.10% respectively on the 15th day. On the 21st day, the average detection rates of morphology and flow cytometry were 13.50% and 10.91%, respectively. The average detection rates of morphology and flow cytometry in 70 lymphoma patients were 7.50% and 10.35% on the 7th day, and 9.00% and 10.35% respectively on the 15th day. The average detection rates of morphology and flow cytometry at 21 days were 6.50% and 5.69%, respectively. The number of CAR-T cells in samples from patients with different diseases reached a peak around the 15th day. Conclusion:The detection rate of CAR-T cells from peripheral blood or bone marrow was significantly higher with the combination of the 2 methods compared to the single method.
ABSTRACT
Objective:To investigate the bacterial distribution of secondary infection and the status of drug resistance in hospitalized patients of hematology department.Methods:The clinical data of 1 125 inpatients in the Hematology Department of the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2019 were retrospectively analyzed, and the distribution of infectious pathogens and the status of drug resistance of these inpatients were analyzed.Results:A total of 9 335 microbial samples from 1 125 inpatients were submitted for examination, among which 1 349 were positive samples. Among 1 349 positive samples, the gram-negative bacteria-positive samples accounted for 66.4% (895/1 349) and the gram-positive bacteria-positive samples accounted for 33.7% (454/1 349); the blood samples accounted for 44.7%(603/1 349), the sputum samples accounted for 33.9% (457/1 349), and the urine samples accounted for 9.4%(127/1 349). The isolated bacteria whose proportion ranked as the top 3 were Escherichia coli (31.0%), Staphylococcus aureus (21.0%) and Klebsiella pneumoniae (18.0%). The drug resistance rate of Escherichia coli to ceftriaxone was as high as 77.2%, and that of Staphylococcus aureus and coagulase-negative Staphylococcus to benzoxicillin was 58.2% and 66.7%, but both had no resistance to vancomycin.Conclusions:There are a wide variety of infectious pathogens in hospitalized patients of hematology department, and the Escherichia coli and Klebsiella pneumonia are predominant. More attention should be paid to antibiotic prescribing training for clinicians to optimize and standardize the use of antibiotics.
ABSTRACT
Histological transformation is a special histological variation in the progression of indolent lymphoma, and is often accompanied by an aggressive enhanced clinical process. Its poor conventional treatment effect, short survival time and poor prognosis have brought great challenges to the clinical treatment. Except for aggressive clinical manifestations and clear histopathological changes, this transformed type of lymphoma is often accompanied by specific imaging, biological metabolism and molecular genetics variations. This paper reviews the progress of histopathology, clinical characteristics, molecular characteristics and treatment strategy of the histological transformation of indolent lymphoma.
ABSTRACT
Objective:To investigate the effect of prognostic nutrition index (PNI) and clinical characteristics on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 236 patients with DLBCL treated in the Affiliated Hospital of Xuzhou Medical University from November 2014 to December 2018 were retrospectively analyzed. X-Tile software and restricted cubic spline (RCS) were used to determine the best cut-off values of PNI, age and hemoglobin; Cox proportional hazard regression model was used for univariate and multivariate analyses; Kaplan-Meier method was used to analyze the overall survival (OS) of patients, and log-rank test was also performed.Results:One-hundred and fifteen of the 236 patients (48.7%) died, with a median OS time of 32 months. The 3-year OS rate was 46%, and the 5-year OS rate was 36%. The best cut-off value of PNI was 49. There was a significant non-linear relationship between PNI and the risk of poor prognosis of DLBCL ( χ2=34.64, P < 0.01); the analysis of the dose-response relationship showed that with the change of PNI, the correlation strength of the risk of poor prognosis declined non-linearly. The best cut-off value of age was 63 years old, and the correlation strength between age and the risk of poor prognosis of DLBCL showed a non-linear upward trend ( χ2=14.86, P=0.022). The best cut-off values of hemoglobin calculated by X-Tile software were 93 g/L and 129 g/L. Multivariate analysis showed that PNI, central nervous system involvement, liver involvement, age, hemoglobin, international prognostic index (IPI) score, and bulky disease were independent influencing factors of OS in DLBCL patients (all P < 0.05). In patients with germinal center B-cell-like (GCB) subtype, bcl-2-positive and bcl-6-positive, there were statistical differences in the 3-year OS rate of patients with PNI < 49 and PNI ≥ 49 (all P < 0.05). Conclusion:PNI has a certain value in the prognosis assessment of DLBCL patients, and PNI ≥ 49 indicates that the patient has a good prognosis.
ABSTRACT
Objective:To explore the prognostic influencing factors of adult lymphoma-associated hemophagocytic syndrome (LAHS) based on multicenter data.Methods:The clinical data of 86 LAHS patients diagnosed in 9 medical centers of Huaihai Lymphoma Working Group from January 2015 to August 2020 were retrospectively analyzed. The optimal cut-off value of continuous variables was obtained based on MaxStat algorithm. Cox proportional hazard regression model was used for univariate and multivariate analyses. Kaplan-Meier method was used for survival analysis, and log-rank test was performed.Results:Among the 86 adult LAHS patients, 50 (58.1%) were males and 36 (41.9%) were females, the median age of the patients was 57 years old (19-76 years old), and the median overall survival (OS) time was 1.67 months (95% CI 0.09- 3.24 months). The most common pathologic type was diffuse large B-cell lymphoma (58 cases, 67.44%). Based on MaxStat algorithm, the optimal cut-off values of age, albumin, serum creatinine, lactate dehydrogenase, fibrinogen and platelet count were 64 years old, 30.1 g/L, 67 μmol/L, 1 045 U/L, 4.58 g/L and 72×10 9/L, respectively. Multivariate analysis showed that patient's age, lactate dehydrogenase, albumin and fibrinogen levels were independent influencing factors for OS (all P < 0.05). Conclusions:LAHS is dangerous and progresses quickly. Patients with age ≥ 64 years old, lactate dehydrogenase ≥ 1 045 U/L, fibrinogen ≥ 4.58 g/L and albumin < 30.1 g/L have poor survival.
ABSTRACT
The complement system is a protein response system with a precise regulation mechanism, and an important part of the body's innate and adaptive immunity. Abnormal complement components, excessive activation and other functional disorders are closely related to the development and progression of lymphoma and immune escape. In addition, the complement system has a certain relevance to clinical treatment, especially immunotherapy. This paper reviews the role of complement system in the occurrence and treatment of lymphoma.
ABSTRACT
As a transmembrane protein, CD47 is widely distributed in a variety of cells. It can bind to signal regulatory protein alpha (SIRPα) on macrophages and release inhibitory signals, thus avoiding phagocytosis of macrophages. In lymphoma cells, the expression of up-regulation of CD47 expression in lymphoma cells is one of the important mechanisms for inducing immune escape, and it is also a potential therapeutic target. This article reviews the research progress of CD47-induced immune escape, monoclonal antibodies targeting CD47 and cellular immunotherapy in the treatment of lymphoma.
ABSTRACT
The microenvironment of lymphoma is an important factor affecting the development of lymphoma, which is involved in regulating the recognition and immune response of lymphoma cells by the immune system. In the era of immunotherapy of lymphoma, the state of microenvironment also affects the effect of monoclonal antibodies, small molecular compounds and other immune targeting drugs on lymphoma cells. Among them, microenvironment-related immune escape is one of the key factors leading to the failure of lymphoma treatment. This article reviews some microenvironment factors such as stromal immune cell subsets, vascular proliferation, hypoxia, immune checkpoint and the recent research progress of immune escape.
ABSTRACT
Diffuse large B-cell lymphoma (DLBCL) is characterized by heterogeneity with respect to morphology, immune phenotype, molecular pathogenesis, clinical presentation and prognosis. With the development of genome and transcriptome sequencing, DLBCL was classified as four subtypes (EZB, BN2, MCD, and N1) or five subtypes (C1-C5). The new molecular pathological typing has a deeper understanding of DLBCL from the levels of genes and molecules which makes the judgment of prognosis more accurate and specific, and it is conducive to the clinical screening of more accurate targeted therapy.
ABSTRACT
EB virus (EBV) is a potential oncogenic virus. About 95% of healthy people are infected with EBV and carry it for all life. EBV can induce host cells clonization and transformation. About 2% of tumors are related to EBV infection. In recent years, EBV-induced lymphocyte clonal transformation and the diagnosis and treatment of EBV-related lymphoproliferative diseases have got some progress.
ABSTRACT
OBJECTIVE@#To study the expression of multiple negative costimulatory molecules on peripheral blood T cells in patients with acute myeloid leukemia (AML) and its affection on prognosis.@*METHODS@#The peripheral blood samples from patients with newly diagnosed AML, complete remission (CR), and no-remission (NR) were collected, the expression levels PD-1、VISTA and TIM-3 in CD4 and CD8 T cells were detected by flow cytometry , and the clinical data of patients were analyzed.@*RESULTS@#The expression levels of PD-1、VISTA and TIM-3 of CD4 and CD8 T cells in the newly diagnosed AML patients were significantly higher than those in control group (P＜0.05). The expression levels of PD-1、TIM-3 and VISTA of CD4 and CD8 T cells in the CR group were significantly lower than those in newly diagnosed and the NR group (P＜0.05). The TIM-3 expression level positively correlated with VISTA expression level of CD4 and CD8 T cells in newly diagnosed AML patients (r=0.85 and 0.73). The VISTA and PD-1 expression level of CD4 T cells in newly diagnosed AML, NR after first induction chemotherapy and high risk patients significantly increased (P＜0.05), the TIM-3 expression level of CD8 T cells in high risk group significantly increased (P＜0.05), and the VISTA expression level of CD8 T cells in CBFβ-MYH11 mutation-positive group significantly decreased (P＜0.05).@*CONCLUSION@#The expression of PD-1、TIM-3 and VISTA in AML peripheral blood T cells may be involved in the immune escape of AML and can be the targets of treatment for acute myeloid leukemia patients.
Subject(s)
Humans , B7 Antigens , CD8-Positive T-Lymphocytes , Flow Cytometry , Hepatitis A Virus Cellular Receptor 2 , Leukemia, Myeloid, Acute , Programmed Cell Death 1 ReceptorABSTRACT
Lymphoma is often accompanied by local infiltration and extranodal involvement, and it is regulated by a variety of factors in the lymphoma microenvironment. Vascular endothelial growth factor (VEGF) plays an important role in regulating angiogenesis and promoting the migration of lymphoma and it is involved in the occurrence and development of lymphoma. This article reviews the progress of VEGF in the development of lymphoma, especially angiogenesis and lymphatic migration, as well as in the treatment and prognosis of lymphoma.
ABSTRACT
CD5-positive diffuse large B-cell lymphoma (CD5+DLBCL) is a special type of DLBCL, which is characterized with later clinical staging, high-risk of relapse in extranodular tissues like bone marrow and central nervous system (CNS).Combined chemotherapy including rituximab and salvage autotransplantation/ allotransplantation can not significantly improve the prognosis. This article reviews the clinicopathological features, the possible pathogenesis, treatment status and dilemma in order to get the better understanding of CD5+DLBCL and avail the early diagnosis and individualized treatment.
ABSTRACT
Epstein-Barr virus (EBV) is one of the most common human herpesviruses, presenting a latent infection in more than 95% of healthy adults. EBV can regulate the differentiation, proliferation and colony formation of infected lymphocytes by coding viral proteins, and it is associated with Burkitt lymphoma, NK/T cell lymphoma, Hodgkin lymphoma, and vascular immunoblastic lymphoma. This article reviews the research progress of EBV in lymphoma transformation.
ABSTRACT
OX40 is a member of the tumor necrosis factor receptor (TNFR) superfamily. In the immune response of the body, OX40 and the OX40 ligand (OX40/OX40L) on the antigen-presenting cell membrane are important co-stimulatory molecules, which can promote the proliferation of T cells. And OX40 also has the dual role of activating and enhancing the T cell immune response. OX40/OX40L is an important target for tumor immunotherapy, and clinical studies of several OX40 agonists are currently underway. This article reviews the immunoregulatory mechanisms of OX40/OX40L and its research progress in lymphoma immunotherapy.
ABSTRACT
Interferon regulatory factor 4 (IRF4) is a member of IRF family, which is mainly expressed in lymphocytes and plays an important role in the development of lymphoma. In addition, it is related with a tentative classification in the name of large B-cell lymphoma with IRF4 gene rearrangement proposed in 2016 updated version of World Health Organization (WHO). This article reviews the structural features, biological functions of IRF4 gene, its role in lymphocyte development, and large B-cell lymphoma with IRF4 gene rearrangement.
ABSTRACT
OBJECTIVE@#To analyze the incidence of hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation and the factors affecting HC, so as to provide clinical evidence for further treatment of HC.@*METHODS@#The HC of 113 patients after allogeneic hematopoietic stem cell transplantation in Affiliated Hospital of Xuzhou Medical University between the years 2014-2016 was analyzed respectively. All cases of HC were divided into HC group and non-HC(control) group. The follow-up time: from preeonditionig day to 180 d after transplantation. The 10 clinical parameters were selected for univariate analysis with COX regression analysis: sex, age (＜25 years and 25 years), primary disease, conditioning regimen with anti-thymoglobulin(ATG), sex-mismatch in recipients, haploidential HSCT, cytomegalovirus (CMV) viremia, EB viremia, graft-versus-host disease (GVHD), and primary disease relapse, the factors significant at the 0.1 level in univariate analysis should be further evaluated by multivariate analysis using a COX regression analysis. The difference was significant at P＜0.05 in multivariate analysis.@*RESULTS@#The HC occured in 31 of 113 patients (27.4%), with 5 cases of grade I (5.5%), 19 of grade II (16.8%), 5 of grade III (4.4%), and 2 of grade IV (1.8%). The median time of HC onset was 37 days (26-70 d) after transplantation. The median duration of HC was 14 days (5-55d). Univariate analysis showed that conditioning with anti-thymoglobulin (ATG) (RR=6.170, 95%CI: 1.875-20.306, P＜0.01), CMV viremia (RR=7.633, 95%CI：2.318-25.133) (P＜0.01), haploidentical HSCT (RR=0.307, 95%CI：0.137-0.686, P＜0.01), GVHD (RR=1.891, 95%CI：0.918-3.898, P＞0.05) were the risk factors for recovery from HC. The multivatiate analysis of above-mentioned risk factors with statistical significance showed that only CMV viremia (RR=4.770, 95%CI: 1.394-16.326, P＜0.05) was the indentified risk factor affecting the recovery from HC.@*CONCLUSION@#Monitoring CMV viremia and antivirotic treatment are effective measurs to prevent the occurrence of HC and promote the recovery from HC.