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1.
Rev. méd. Chile ; 151(8): 992-998, ago. 2023. ilus
Article in Spanish | LILACS | ID: biblio-1565695

ABSTRACT

INTRODUCCIÓN: El Linfoma de Hodgkin (LH) es una causa prevalente de morbilidad por Cáncer Hematológico en el mundo y también en nuestro entorno. OBJETIVOS: Mostrar la experiencia de diez años tratando el LH en un centro docente chileno. Adicionalmente, exponer el rendimiento de diagnóstico del PET CT y la Biopsia de Médula Ósea. MATERIAL Y MÉTODOS: Se realiza un estudio de Cohorte retrospectivo para recopilar datos y resultados de los pacientes tratados en nuestro centro. RESULTADOS: Se analizaron 82 pacientes (edad promedio 35 años. Razón entre hombres y mujeres de 1,9:1). La sobrevida libre de progresión de 88,6% y 66,4% para estadios localizados y avanzados respectivamente. El PET como estrategia de etapificación tuvo mejor sensibilidad al comparar con la Biopsia de Médula. CONCLUSIONES: El resultado clínico de los pacientes tratados en este centro docente chileno fueron comparables a la literatura internacional. Adicionalmente, el PET CT evidenció ser una herramienta superior en el diagnóstico y etapificación superior a la biopsia en nuestros pacientes.


INTRODUCTION: Hodgkin Lymphoma (HL) is a prevalent hematological cancer in the world and Chile. OBJECTIVES: Show the experience of 10 years treating HL in a Chilean academic center. Additionally, it exposes the diagnostic performance of PET CT and Bone Marrow Biopsy. MATERIAL AND METHODS: We conducted a retrospective cohort study to collect data and outcomes of patients treated in our center. RESULTS: 82 patients were analyzed (Average age, 35 years old; the ratio between men and women was 1.9:1). Progression-free survival was 88.6% and 66.4% for localized and advanced stages, respectively. PET as a staging strategy had better sensitivity than Marrow Biopsy. CONCLUSIONS: The clinical results of the patients treated in this Chilean teaching center were comparable to the international literature. Additionally, PET CT proved to be a superior tool in diagnosis and staging compared to biopsy in our patients.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Hodgkin Disease/pathology , Hodgkin Disease/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Neoplasm Staging , Biopsy , Bone Marrow/pathology , Bone Marrow/diagnostic imaging , Chile , Retrospective Studies , Sensitivity and Specificity
2.
Article in Chinese | WPRIM | ID: wpr-971133

ABSTRACT

OBJECTIVE@#To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively.@*RESULTS@#4 patients had bone marrow, spleen and lymph nodes involvement, 2 patients had skin lesions, and 3 patients had central nervous system infiltration. Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients, and CD304 in 3 patients. One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again. One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine.@*CONCLUSION@#The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.


Subject(s)
Humans , Dendritic Cells , Retrospective Studies , Skin Neoplasms/pathology , Antineoplastic Agents/therapeutic use , Bone Marrow/pathology , Myeloproliferative Disorders , Hematologic Neoplasms/drug therapy
3.
Article in English | WPRIM | ID: wpr-981081

ABSTRACT

OBJECTIVE@#Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL.@*METHODS@#A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.@*RESULTS@#The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively.@*CONCLUSION@#18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.


Subject(s)
Humans , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18 , Bone Marrow/pathology , Retrospective Studies , Positron-Emission Tomography/methods , Lymphoma, Large B-Cell, Diffuse/pathology
4.
Article in Chinese | WPRIM | ID: wpr-981299

ABSTRACT

Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.


Subject(s)
Humans , Animals , Mice , Multiple Myeloma/pathology , Bone Marrow/pathology , Disease Models, Animal , Drug Resistance , Tumor Microenvironment
5.
Article in Chinese | WPRIM | ID: wpr-981699

ABSTRACT

OBJECTIVE@#To explore relationship between bone marrow edema(BME) and osteoporosis in patients with severe knee osteoarthritis.@*METHODS@#Unmatched case-control study was conducted. Totally 160 patients with severe knee osteoarthritis who had undergone knee magnetic resonance imaging (MRI) and bone mineral density examination (BMD) from January 2020 to March 2021 were included. Eighty patients complicated with BME were included in BME group, and 80 patients without BME were selected as NBME group. In BME group, there were 12 males and 68 females, aged from 51 to 80 years old with an average of(66.58±8.10) years old;the courses of disease ranged from 5 to 40 months with an average of (15.61±9.25) months;body mass index(BMI) ranged from 21.81 to 34.70 with an average of (27.79±3.00) kg·m-2;25 patients classified to grade Ⅲ and 55 patients grade Ⅳ according to Kellgren- Lawrence(K-L). In NBME group, there were 15 males and 65 females, aged from 50 to 80 years old with an average of(67.82±8.05) years old;the course of disease ranged from 6 to 37 months with an average of(15.75±8.18) months;BMI ranged from 21.39 to 34.46 with an average of (28.26±3.13) kg·m-2;25 patients were K-L Ⅲ and 55 patients with K-L Ⅳ. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score(WORMS). Osteoporosis was diagnosed and BMD was evaluated by DXA T value. To explore the relationship between bone marrow edema and osteoporosis by comparing prevalence rate of osteoporosis between two groups, and to further explore relationship between BME and BMD by Spearman correlation analysis of BME WORMS score and DXA T value in BME group.@*RESULTS@#The complete case data were obtained on the first diagnosis, and there was no significant difference in sex, age, courses of disease and BMI between two groups (P>0.05). The proportion of K-L Ⅳ in BME group was significantly higher than that in NBME (P<0.05). The prevalence rate of osteoporosis in BME group was significantly higher than in NBME group with the same K-L grade (P<0.001), and there was a strong negative correlation between BME WORMS score and DXA BMD T value (r=-0.812, |r|=0.812 >0.8, P<0.001).@*CONCLUSION@#Osteoporosis is one of the risk factors of bone marrow edema in patients with severe knee osteoarthritis, and the lower the bone mineral density is, the easier it is to be complicated with bone marrow edema.


Subject(s)
Male , Female , Humans , Osteoarthritis, Knee/diagnostic imaging , Bone Marrow/pathology , Case-Control Studies , Bone Marrow Diseases/etiology , Osteoporosis/complications , Edema/etiology , Magnetic Resonance Imaging/methods
6.
Article in Chinese | WPRIM | ID: wpr-981727

ABSTRACT

OBJECTIVE@#To investigate the relationship between bone marrow edema and pathological changes, symptoms and signs of severe knee osteoarthritis.@*METHODS@#From January 2020 to March 2021, 160 patients with severe knee osteoarthritis who underwrent MRI of the knee at the Department of Bone and Joint, Wangjing Hospital, China Academy of Chinese Medical Sciences were included. Eighty patients with bone marrow edema were selected as the case group, including 12 males and 68 females, aged from 51 to 80 years old with an average of (66.58±8.10) years old, the duration of disease 5 to 40 months with an average of (15.61±9.25) months. Eighty patients without bone marrow edema were selected as the control group, including 15 males and 65 females, aged from 50 to 80 years old with an average of (67.82±8.05) years old, the duration of disease 6 to 37 months with an average of (15.75±8.18) months, BMI was (28.26±3.13) kg·m-2 ranged from 21.39 to 34.46 kg·m-2. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score (WORMS). The degree of knee osteoarthritis was evaluated by Kellgren- Lawrence(K-L) grade and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). The degree of joint pain was evaluated by visual analogue scale(VAS) and WOMAC pain score, the joint signs were evaluated by tenderness, percussion pain, joint swelling and joint range of motion. To explore the relationship between bone marrow edema and knee osteoarthritis, the prevalence of bone marrow edema and K-L grade were compared between the two groups. Furthermore the WORMS score and WOMAC index, pain-related score, and sign-related score correlation coefficient were analyzed to further explore the relationship between bone marrow edema and knee osteoarthritis index, joint pain symptoms and signs.@*RESULTS@#There was 68.75% (55/80) of the patients in the case group were in K-L grade Ⅳ, and 52.5% (42/80) in the control group, indicating a higher proportion of patients with grade Ⅳ in the case group than the control group (χ2=4.425, P<0.05). In the case group, there was a strong correlation between bone marrow edema WORMS score and knee osteoarthritis WOMAC index. (r=0.873>0.8, P<0.001), a moderate correlation between WORMS score and VAS score and WOMAC pain score(r=0.752, 0.650>0.5, P<0.001), a moderate correlation between WORMS score and percussion pain score (r=0.784>0.5, P<0.001), and a weak correlation between WORMS score and VAS and tenderness score, joint swelling score and joint range of motion score (r=0.194, 0.259, 0.296<0.3, P<0.001).@*CONCLUSION@#Our study suggests that severe knee osteoarthritis is associated with an increased risk of bone marrow edema. Bone marrow edema can also lead to knee osteoarthritis joint pain, with percussion pain being a positive sign, but tenderness, joint swelling and limitation of activity are not significantly related to bone marrow edema.


Subject(s)
Male , Female , Humans , Osteoarthritis, Knee/pathology , Bone Marrow/pathology , Knee Joint/diagnostic imaging , Bone Marrow Diseases/etiology , Pain/pathology , Arthralgia , Edema/pathology
7.
Chinese Journal of Hematology ; (12): 495-500, 2023.
Article in Chinese | WPRIM | ID: wpr-984650

ABSTRACT

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.


Subject(s)
Male , Adult , Humans , Aged , Lymphoma, Mantle-Cell/drug therapy , Prognosis , Retrospective Studies , Bone Marrow/pathology , Risk Factors
8.
Journal of Experimental Hematology ; (6): 1044-1049, 2023.
Article in Chinese | WPRIM | ID: wpr-1009962

ABSTRACT

OBJECTIVE@#To explore the diagnostic value of 18F-FDG PET/CT in bone marrow infiltration (BMI) of newly diagnosed diffuse large B-cell lymphoma (DLBCL), compared with the results of bone marrow biopsy (BMB) and investigate whether the BMI diagnosed by 18F-FDG PET/CT and other factors have independent prognostic values.@*METHODS@#Ninety-four newly diagnosed DLBCL patients who underwent PET/CT in Clinical Medical College of Shanghai General Hospital of Nanjing Medical University were included. BMB was performed within 2 weeks before or after PET/CT, and standardized treatment was performed after PET/CT. The manifestations of bone marrow (BM) FDG uptake were recorded. The diagnostic criteria of BMI were BMB positive or focal BM FDG uptake confirmed by imaging follow-up. The relationship between clinical features and BM FDG uptake and the values of PET/CT and BMB in the diagnosis of BMI was analyzed. The progression-free survival (PFS) was analyzed by Kaplan-Meier survival curves, log-rank test was used to compare PFS rate, and Cox regression model was used to analyze the independent risk factors affecting PFS.@*RESULTS@#Among 94 DLBCL patients, 34 patients showed focal BM uptake (fPET), 7 patients showed super BM uptake (sBMU), 11 patients showed diffuse homogenous uptake higher than liver (dPET), and the other 42 patients had normal BM uptake (nPET) (lower than liver). BMB positive was found in all sBMU patients, in 20.6%(7/34) of fPET patients, and in 27.3% (3/11) of dPET patients. All nPET patients had negative BMB results. dPET patients were associated with lower hemoglobin level and leukocyte count compared with nPET group (P < 0.001, P =0.026). Compared with fPET patients, sBMU patients were more likely to have B symptoms and elevated lactate dehydrogenase (LDH). A total of 44 patients were diagnosed BMI, including 17 cases with BMB+. The sensitivity and specificity of BMB in the diagnosis of BMI was 38.6% (17/44) and 100% (50/50), respectively. Using fPET and sBMU as criteria of PET BMI, the diagnostic sensitivity and specificity of PET/CT was 93.2% (41/44) and 100% (50/50), respectively. Kaplan-Meier analysis showed that there was no significant difference in 2-year PFS rate between nPET and dPET patients (P >0.05), while sBMU patients had lower 2-year PFS rate compared with fPET patients (P < 0.001). Multivariate analysis showed that higher Ann Arbor stage (HR=9.010, P =0.04) and sBMU (HR=3.964, P =0.002) were independent risk factors affecting PFS.@*CONCLUSIONS@#Increased BM FDG uptake of DLBCL can be manifested as dPET, fPET and sBMU. fPET and sBMU can replace BMB to diagnose BMI. Although dPET cannot completely exclude the possibility of BMI, it does not affect the prognosis, so it can be diagnosed as PET BMI negative. sBMU is an independent prognostic risk factor.


Subject(s)
Humans , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18 , Prognosis , Bone Marrow/pathology , Retrospective Studies , China , Positron-Emission Tomography/methods , Lymphoma, Large B-Cell, Diffuse/pathology , Biopsy
9.
Journal of Experimental Hematology ; (6): 1113-1118, 2023.
Article in Chinese | WPRIM | ID: wpr-1009969

ABSTRACT

OBJECTIVE@#To construct a myeloproliferative neoplasms (MPN) transplanted mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation, and establish a systematic evaluation system to verify the success of model construction.@*METHODS@#The bone marrow c-kit+ cells of the mice were obtained by the following steps: The mice were killed by cervical dislocation, the femur, tibia and ilium were separated, and the bone marrow cells were collected. The c-kit+ cells were sorted after incubation with CD117 magnetic beads. The method of constructing mouse primary mutant cells is as follows: A gene mutation vector with a GFP tag was constructed by the retroviral system, and the retroviral vector was packaged into the Platinum-E cells to obtain the virus supernatant, and then used it to infect the c-kit+ cells of mice. The MPN mouse model was constructed as follows: the mouse primary c-kit+ cells containing the mutant genes were collected after infection, and then transplanted them via the tail vein into the female recipient mice of the same species which were irradiated with a lethal dose of gamma rays (8.0 Gy). The MPN mouse model was evaluated as follows: After transplantation, the peripheral blood of the mice was regularly collected from the tail vein to perform the complete blood count test, and the size of spleen and the degree of bone marrow fibrosis were estimated.@*RESULTS@#The mouse c-kit+ cells with the mutant genes were successfully obtained from the bone marrow. MPN mouse model was successfully constructed: The peripheral blood cells of the MPN-transplanted mice carried exogenous implanted GFP-positive cells, and the white blood cells (WBC), platelet (PLT) and hematocrit (HCT) were all increased; the body weight loss, and the water and food intake were reduced in the transplanted mice; further pathological analysis showed that the transplanted mice displayed splenomegaly and bone marrow fibrosis. These results suggested that the MPN mouse model was successfully constructed. According to the common and different characteristics of the three MPN mouse model, a preliminary evaluation system for judging the success of MPN mouse model construction was summarized, which mainly included the following indicators, for example, the proportion of GFP-positive cells in the peripheral blood of mice; WBC, PLT and HCT; the degree of spleen enlargement and the bone marrow fibrosis.@*CONCLUSION@#The MPN mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation is successfully established by retroviral system, which can provide an important experimental animal model for the research of MPN pathogenesis and drug-targeted therapy.


Subject(s)
Female , Mice , Animals , Primary Myelofibrosis , Myeloproliferative Disorders/genetics , Bone Marrow/pathology , Mutation , Disease Models, Animal , Neoplasms , Janus Kinase 2/genetics
10.
Journal of Experimental Hematology ; (6): 1639-1646, 2023.
Article in Chinese | WPRIM | ID: wpr-1010017

ABSTRACT

OBJECTIVE@#To analyze the flow immunophenotype and clinical characteristics of leukemia patients with positive SET-CAN fusion gene.@*METHODS@#A total of 7 newly diagnosed acute leukemia patients with SET-CAN fusion gene admitted to Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from February 2016 to February 2020 were collected. Multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of SET-CAN fusion gene. The immunophenotype was detected by four-color flow cytometry. The case information of 17 literatures published at home and abroad was extracted for statistical analysis.@*RESULTS@#Among the 7 patients, 2 cases were diagnosed as mixed phenotype acute leukemia (MPAL), 2 cases as acute myeloid leukemia (AML), and 3 cases as T-acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). Leukemia cells in bone marrow specimens of all cases expressed or partially expressed CD34, CD33 and CD7. CD5 and cytoplasmic CD3 were expressed in 5 patients except 2 patients diagnosed with AML. Bone marrow and lymph node specimens were both detected in 2 patients, and the immunophenotypes of the two specimens were not completely consistent, with differences in lineage or maturity related markers. Two patients with MPAL showed differentiated response to treatment. One AML patient gave up treatment, and another AML patient with FLT3-ITD gene mutation had a poor prognosis. All three T-ALL/LBL patients maintained a long duration of remission after induced remission, and one case underwent allogeneic hematopoietic stem cell transplantation.@*CONCLUSIONS@#There are common characteristics of immunophenotype in patients with positive SET-CAN fusion gene. Differential expression of immunophenotype in samples from different parts is observed in some cases. The prognosis of these diseases varies.


Subject(s)
Humans , Leukemia, Myeloid, Acute/pathology , Bone Marrow/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Antigens, CD34 , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Immunophenotyping
11.
Journal of Experimental Hematology ; (6): 1720-1725, 2023.
Article in Chinese | WPRIM | ID: wpr-1010028

ABSTRACT

OBJECTIVE@#To explore the value of multiple detection methods based on histopathology and supplemented by bone marrow or peripheral blood sample detections in the comprehensive diagnosis of mantle cell lymphoma (MCL).@*METHODS@#The clinical, immunophenotypic, pathologic, cytogenetic and molecular features of 153 newly diagnosed MCL patients admitted to the hematology department of our hospital from May 2009 to September 2022 were analyzed.@*RESULTS@#144 (96.6%) of the 149 MCL patients who underwent marrow or peripheral blood IGH/CCND1 FISH detection at initial diagnosis were positive, of which 36 cases (24.2%) had a low proportion positive. The immunophenotypes in 115 patients were analyzed by flow cytometry (FCM), 89 cases (77.4%) conformed to MCL while 23 cases (20.0%) were initially diagnosed as B-cell lymphoproliferative disorders (B-LPD). Of the 75 cases who performed bone marrow biopsy, 50 cases (66.7%) had morphological and immunophenotypic characteristics consistent with MCL, 15 cases (20.0%) were classified as B-LPD, and 10 cases with no obvious abnormality. 77 patients underwent histopathology examination, of which 73 cases (94.8%) had typical clinicopathological features of MCL, including 2 CCND1 negative MCL, 2 pleomorphic variants, 5 pleomorphic variants and 4 cases diagnosed as other leukemia or lymphoma. Among 153 cases of MCL, 128 cases were classic MCL(cMCL), and another 25 cases (16.3%) were diagnosed as leukemic non-lymph node MCL (lnnMCL). The incidence of IGHV mutation, TP53 mutation and CD23 expression positive were significantly different between cMCL and lnnMCL.@*CONCLUSION@#Histopathology is still the main standard for the diagnosis of cMCL, and detection based on bone marrow or peripheral blood samples is an important means for the diagnosis of lnnMCL. Single marker or examination can cause a certain proportion of misdiagnosis. The accurate diagnosis of MCL depends on a combination of multiple detection methods.


Subject(s)
Adult , Humans , Lymphoma, Mantle-Cell/genetics , Bone Marrow/pathology , Leukemia/pathology , Mutation , Immunophenotyping
12.
Journal of Experimental Hematology ; (6): 1739-1744, 2023.
Article in Chinese | WPRIM | ID: wpr-1010031

ABSTRACT

OBJECTIVE@#To study the expression level of nicotinamide phosphoribosyltransferase (NAMPT) in multiple myeloma (MM), its relationship with clinical indicators, prognosis and potential role.@*METHODS@#Immunohistochemical staining was used to detect the expression of NAMPT in bone marrow biopsies of patients with newly diagnosed multiple myeloma (NDMM) and patients with iron deficiency anemia (IDA) hospitalized during the same period. According to the median expression level of NAMPT, NDMM patients were divided into high expression group and low expression group. The correlation between NAMPT expression level and clinical baseline data was analyzed, and survival analysis was performed to evaluate the relationship between NAMPT expression level and prognosis. The GSE24080 and GSE19784 datasets were used to analyze the effect of NAMPT on the prognosis. Gene set enrichment analysis (GSEA) explored the possible mechanism of NAMPT involved in MM cell function.@*RESULTS@#The mean staining intensity of NAMPT in bone marrow tissue of 31 NDMM patients was 0.007±0.002, and that of 10 IDA patients was 0.002±0.002 (P < 0.05). The median expression level of NAMPT was 0.0041 in NDMM patients, and the mean staining intensity of high expression group and low expression group was 0.007±0.005 and 0.002±0.001, respectively (P < 0.001). There were certain differences in lactate dehydrogenase (LDH), C-reactive protein (CRP) and ISS staging between high expression group and low expression group (P < 0.001), while no significant differences in other indicators. The overall response rate (ORR) of high expression group was significantly lower than that of low expression group (P < 0.001). The median survival time of patients in high expression group was significantly shorter than that in low expression group (P =0.024). The results of bioinformatics analysis showed that the event-free survival (EFS) rate and overall survival (OS) rate of low NAMPT group were both higher than high NAMPT group (P =0.037, P =0.009), and NAMPT was an independent prognostic factor for EFS and OS (P =0.006, P =0.020). GSEA suggested that NAMPT might affect MM cell function through mTORC1 signaling pathway.@*CONCLUSIONS@#The expression level of NAMPT in bone marrow of NDMM patients is significantly higher than that of IDA patients, and the high expression of NAMPT may be correlated with late ISS stage, and high level of LDH and CRP. Patients with high expression of NAMPT have worse response to bortezomib and survival time may be shorter. NAMPT may be involved in the occurrence and development of MM through mTORC1 signaling pathway.


Subject(s)
Humans , Multiple Myeloma/genetics , Bone Marrow/pathology , Nicotinamide Phosphoribosyltransferase , Clinical Relevance , Prognosis , Mechanistic Target of Rapamycin Complex 1
13.
Journal of Experimental Hematology ; (6): 1780-1786, 2023.
Article in Chinese | WPRIM | ID: wpr-1010037

ABSTRACT

OBJECTIVE@#To understand the biological characteristics of polycythemia vera (PV) patients with myeloid fibroplasia, and further analyze the risk factors affecting myeloid fibroplasia in PV patients, so as to provide ideas for predicting the occurrence of myeloid fibroplasia in PV patients.@*METHODS@#Forty patients with PV in the Department of Hematology, Xiyuan Hospital of China Academy of Chinese Medical Sciences were collected and divided into two groups, with (hyperplasia group) and without (Non-proliferative group) hyperplasia of bone marrow fibers. The differences of basic clinical characteristics, blood routine, biochemistry, bone marrow cells, coagulation function and other indicators between the two groups were compared, and the independent risk factors affecting the proliferation of bone marrow fibrous tissue in PV patients were further analyzed by multivariate regression.@*RESULTS@#Compared with Non-proliferative group, the JAK2 mutation rate (95% vs 70%,P=0.037), eosinophilic cell count (0.19 vs 0.11, P=0.047) and eosinophilic percentage (1.84 vs 1.27, P=0.001) in PV patients with hyperplasia were significantly increased, triglycerides (1.55 vs 1.91, P=0.038) and low-density lipoprotein (1.50 vs 3.08, P=0.000) were significantly reduced, bone marrow hematopoietic volume (0.85 vs 0.6, P=0.001), granulocyte/erythrocyte ratio (3.40 vs 1.89, P=0.033), lymphocyte/erythrocyte ratio (0.60 vs 0.42, P=0.033), and granulocyte+lymphocyte/erythrocyte ratio (3.72 vs 2.37, P=0.026) were significantly increased, thrombin time (18.84 vs 18.12, P=0.043) was significantly prolonged. Multivariate regression analysis results showed that peripheral blood eosinophil ≥2% and low-density lipoprotein ≤2 mmol/L were independent risk factors for bone marrow fibrous tissue hyperplasia in PV patients (P<0.05).@*CONCLUSION@#Increased proportion of peripheral blood eosinophils and decreased low density lipoprotein are risk factors for bone marrow fibrous tissue hyperplasia in PV patients.


Subject(s)
Humans , Bone Marrow/pathology , Polycythemia Vera , Hyperplasia/pathology , Granulocytes/pathology , Janus Kinase 2/genetics , Risk Factors , Lipoproteins, LDL , Polycythemia/pathology
14.
Chinese Journal of Hematology ; (12): 107-114, 2022.
Article in Chinese | WPRIM | ID: wpr-929541

ABSTRACT

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.


Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Bone Marrow/pathology , Exons , Janus Kinase 2/genetics , Mutation , Mutation, Missense , Polycythemia Vera/genetics
15.
Rev. Bras. Cancerol. (Online) ; 67(3): e-091228, 2021.
Article in Portuguese | LILACS | ID: biblio-1292092

ABSTRACT

Introdução: O potencial de transformação maligna de células-tronco hematopoiéticas portadoras de mutações no gene glicosilfostatidilinositolclasse A (PIG-A) para leucemias agudas, embora raro, já é bem descrito na literatura. Objetivo: Neste estudo, porém, buscou-se evidenciar pela primeira vez na literatura o surgimento ou a manutenção de clones de hemoglobinúria paroxística noturna (HPN) em pacientes diagnosticados com leucemia aguda ou ainda após o início do tratamento quimioterápico. Método: A pesquisa de clones de HPN foi realizada por citometria de fluxo em blastos, hemácias, granulócitos ou monócitos de 47 amostras de sangue periférico e medula óssea de pacientes submetidos à investigação diagnóstica ou acompanhamento terapêutico, provenientes de dois hospitais oncológicos e públicos de Belém, no período de dezembro de 2017 a dezembro de 2018. Resultados: A presença de clones de HPN foi observada em 19/47 (40,4%) amostras de pacientes, em investigação diagnóstica ou acompanhamento terapêutico, que realizaram pelo menos um estudo de acompanhamento terapêutico e ainda tiveram o surgimento ou a manutenção do clone de HPN mesmo após iniciado o tratamento quimioterápico. Conclusão: Foi possível evidenciar, de forma primária, a presença de clones de HPN em pacientes diagnosticados com leucemia aguda tanto no período de investigação diagnóstica como durante o acompanhamento terapêutico, independentemente da ontogenia celular. Sem, porém, que se possa ainda avaliar a importância da presença desses clones de HPN para a evolução da doença primária, prognóstico ou necessidade de tratamento específico.


Introduction: The potential for malignant transformation of hematopoietic stem cells carrying mutations in theglycosylphosphatidylinositol class A (PIG-A) gene for acute leukemias, although rare, is already well described in the literature. Objective: In this study, however, it was attempted to show for the first time in the literature the emergence or maintenance of paroxysmal nocturnal hemoglobinuria (PNH) clones in patients diagnosed with acute leukemia or even after the beginning of the chemotherapy treatment. Method: The search of PNH clones was performed by flow cytometry in blasts, erythrocytes, granulocytes or monocytes of 47 samples of peripheral blood and bone marrow from patients undergoing diagnostic investigation or therapeutic follow-up in two oncological and public hospitals in Belém, from December 2017 to December 2018. Results: The presence of PNH clones was observed in 19/47 (40.4%) patient samples, in diagnostic investigation or therapeutic follow-up, who participated of at least one therapeutic follow-up study and still experience the appearance or maintenance of the PNH clone even after the beginning of the chemotherapy treatment. Conclusion: Primarily, it was possible to demonstrate the presence of PNH clones in patients diagnosed with acute leukemia both during the diagnostic investigation period and therapeutic follow-up, regardless of cell ontogeny. However, the importance of the presence of these PNH clones for the evolution of the primary disease, prognosis or need for specific treatment was not evaluated yet.


Introducción: El potencial de transformación maligna de las células madre hematopoyéticas que portan mutaciones en el gen glicosofosfatidilinositol (GPI) clase A (PIGA) para las leucemias agudas, aunque raro, ya está bien descrito en la literatura. Objetivo: En este estudio, sin embargo, buscamos mostrar por primera vez en la literatura la aparición o mantenimiento de clones de HPN en pacientes diagnosticados de leucemia aguda o incluso después del inicio de la quimioterapia. Método: La investigación de clones de hemoglobinuria paroxística nocturna (HPN) se realizó mediante citometría de flujo en blastos, eritrocitos, granulocitos o monocitos de 47 muestras de sangre periférica y médula ósea de pacientes sometidos a investigación diagnóstica o seguimiento terapéutico de dos hospitales oncológicos y públicos de Belém, durante el período. de diciembre de 2017 a diciembre de 2018. Resultados: La presencia de clones HPN se observó en 19/47 (40,4%) muestras de pacientes, en investigación diagnóstica o seguimiento terapéutico, que realizaron al menos un estudio de seguimiento terapéutico y aún tenían la aparición o mantenimiento del clon HPN incluso después de iniciado el tratamiento de quimioterapia. Conclusión: Se pudo evidenciar, de forma primaria, la presencia de clones de HPN en pacientes diagnosticados de leucemia aguda tanto durante el período de investigación diagnóstica como durante el seguimiento terapéutico, independientemente de la ontogenia celular. Sin embargo, no podemos todavía evaluar la importancia de la presencia de estos clones de HPN para la evolución de la enfermedad primaria, el pronóstico o la necesidad de un tratamiento específico.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Leukemia/diagnosis , Hemoglobinuria, Paroxysmal/blood , Bone Marrow/pathology , Leukemia/drug therapy , Clone Cells , Flow Cytometry , Hemoglobinuria, Paroxysmal/diagnosis
16.
Rev. Soc. Bras. Clín. Méd ; 18(4): 217-221, DEZ 2020.
Article in Portuguese | LILACS | ID: biblio-1361632

ABSTRACT

A sarcoidose caracteriza-se como doença granulomatosa que acomete diferentes órgãos humanos, especialmente os pulmões, sendo sua patogênese pouco conhecida. No caso em questão, a paciente iniciou com sintomas inespecíficos, como fraqueza, perda ponderal e tosse seca esporádica, sendo internada para extensão da propedêutica. Sugeriu-se como hipótese diagnóstica inicial possível quadro de mieloma múltiplo, tendo em vista a anemia, a disfunção renal, a hipercalcemia e, sobretudo, as lesões osteolíticas apresentadas pela paciente. Todavia, o diagnóstico de sarcoidose foi selado a partir das biópsias de medula óssea e de linfonodo inguinal, que evidenciaram mielite e linfadenite granulomatosas, respectivamente. A terapêutica instituída baseou-se na administração de corticosteroides e em medidas de redução da calcemia. A paciente recebeu alta, com melhora do quadro clínico, para acompanhamento ambulatorial da doença. Conclui-se que a sarcoidose não possui tratamento curativo, mas a terapêutica imunossupressora é eficaz no controle da progressão da enfermidade, fazendo com que o paciente tenha um prognóstico favorável.


Sarcoidosis is characterized as a granulomatous disease that affects different human organs, especially the lungs, and its pathogenesis is little known. In this case, the patient started with nonspecific symptoms, such as weakness, weight loss, and sporadic dry cough, being hospitalized for extension of the propaedeutics. The initial diagnostic hypothesis suggested was a possible case of multiple myeloma, based on the anemia, renal dysfunction, hypercalcemia and, above all, the osteolytic lesions presented by the patient. However, the diagnosis of sarcoidosis was made after bone marrow and inguinal lymph node biopsies that showed granulomatous myelitis and lymphadenitis, respectively. The therapy instituted was based on the administration of corticosteroids and on measures to reduce the level of calcium. The patient was discharged, with clinical improvement, for outpatient follow-up of the disease. It is concluded that sarcoidosis has no curative treatment, but immunosuppressive therapy is effective in controlling the progression of the disease, giving the patient a favorable prognosis.


Subject(s)
Humans , Female , Aged , Sarcoidosis/diagnostic imaging , Rare Diseases/diagnostic imaging , Multiple Myeloma/diagnostic imaging , Sarcoidosis/drug therapy , X-Rays , Biopsy , Blood Protein Electrophoresis , Bone Marrow/pathology , Prednisone/therapeutic use , Tomography, X-Ray Computed , Adrenal Cortex Hormones/therapeutic use , Creatinine/blood , Diagnosis, Differential , Acute Kidney Injury/diagnosis , Hypercalcemia , Anemia , Lymph Nodes/pathology , Lymphadenitis/diagnosis , Myelitis/diagnosis
17.
J. health med. sci. (Print) ; 6(3): 191-198, jul.-sept. 2020. tab, ilus, graf
Article in Spanish | LILACS | ID: biblio-1379934

ABSTRACT

La biopsia de médula ósea (BMO) es un procedimiento invasivo que ha ganado campo en la práctica médica ya que se realiza para el diagnóstico, estadificación y seguimiento de enfermedades hematológicas y no hematológicas, benignas o neoplásicas, entre otros. El objetivo fue establecer el rol de la BMO en las hemopatías en Pediatría en el ION SOLCA Guayaquil- Ecuador. Se utilizó un estudio descriptivo retrospectivo donde se incluyeron a todos los pacientes pediátricos menores de 18 años de edad que se sometieron a BMO, desde Julio de 2014 a Julio de 2017 en el hospital. De las 1511 BMO realizadas en el periodo de estudio, 869 correspondieron a biopsias pediátricas, de las cuales el 57,08% fueron varones. La edad mediana fue 5 (RIC: 3-10) años. El tamaño promedio de la BMO fue de 0,74 (0,1-2,5) cm, con una celularidad media de 20% (4-100%). El motivo de consulta más frecuente fue la fiebre (22,67%). En el hemograma se detectó más frecuentemente bicitopenia (44,65%) y pancitopenia (24,63%). La Leucemia Linfoblástica Aguda (LLA) fue la enfermedad hematológica maligna más comúnmente encontrada (19,59%). Solo un 0,12% correspondió al grupo de Síndromes Mielodisplásicos (SMD), mientras que un 0,23% fueron Neoplasias Mieloproliferativas (NMP). El 26,93% de las biopsias no fueron aptas para el diagnóstico, el 48,45% se encontraron libres de enfermedad de base. La enfermedad oncohematológica pediátrica más frecuente es la LLA, mientras que los SMD y las NMP son infrecuentes. El rol del patólogo y de la BMO es fundamental en el diagnóstico de las enfermedades hematológicas, siempre en integración con la clínica y los exámenes complementarios.


Bone marrow biopsy (BMB) is an invasive procedure that has gained ground in medical practice since it is performed for the diagnosis, staging and monitoring of hematological and non-hematological, benign or neoplastic diseases, among others. This work aims to establish the role of the BMB in hematological diseases in Pediatrics in the ION SOLCA Guayaquil ­ Ecuador. A non-experimental design study, descriptive type was used, that included all pediatric patients under 18 years of age who submitted a BMB, from July 2014 to July 2017 in the hospital. Of the 1511 BMB performed in the study period, 869 corresponded to pediatric biopsies, of which 57.08% belong to male patients. The median age was 5 (interquartile range: 3 - 10) years. The average size of the BMB was 0.74 (0.1 - 2.5) cm, with an average cellularity of 20% (4 - 100%). The most frequent reason for consultation was fever (22.67%). In the complete blood count, bicytopenia (44.65%) and pancytopenia (24.63%) were detected most commonly. Acute Lymphoblastic Leukemia (ALL) was the most frequent malignant hematologic disease (19.59%). Only 0.12% corresponded to the group of Myelodysplastic Syndromes (MDS), while 0.23% were Myeloproliferative Neoplasms (MPN). 26.93% of the biopsies were not apt for diagnosis, 48.45% were free of base disease. The most cfrequent pediatric onco-hematologic disease is ALL, while MDS and MPN are infrequent. The role of the pathologist and the BMP is fundamental in the diagnosis of hematological diseases, always in integration with the clinic and complementary examinations.


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Bone Marrow/pathology , Bone Marrow Neoplasms/secondary , Bone Marrow Neoplasms/epidemiology , Signs and Symptoms , Biopsy , Blood Cell Count , Bone Neoplasms/diagnosis , Bone Neoplasms/pathology , Megakaryocytes/metabolism , Age and Sex Distribution , Myeloproliferative Disorders/diagnosis
18.
Rev. Soc. Bras. Clín. Méd ; 17(2): 101-105, abr.-jun. 2019. ilus., graf.
Article in Portuguese | LILACS | ID: biblio-1026523

ABSTRACT

O hemangioma esplênico, tumor benigno mais frequente do baço, porém, por vezes de difícil diagnóstico, pode integrar a síndrome de Kasabach-Merritt, afecção rara e potencialmente fatal, descrita como associação entre hemangioma, trombocitopenia e coagulopatia de consumo. Apresentamos um caso de paciente de 73 anos em acompanhamento com a hematologia por trombocitopenia crônica a princípio idiopática, que evoluiu com dor abdominal, anemia e derrame pleural. Foi realizada tomografia computadorizada de abdome, que evidenciou massa esplênica sólida heterogênea. A paciente foi submetida a esplenectomia total videolaparoscópica e evoluiu com melhora da dor abdominal e normalização da série plaquetária, sem recorrência do derrame pleural após o procedimento. A raridade e a complexidade do caso, somadas à dificuldade diagnóstica e à abordagem terapêutica, foram fatores que corroboraram para a apresentação desse caso. (AU)


Splenic hemangioma, the most common, but sometimes hard to diagnose, benign tumor of the spleen may integrate Kasabach- Merritt syndrome, a rare and potentially fatal condition described as an association ofhemangioma, thrombocytopenia and consumption coagulopathy. We present a case of a 73-year-old female patient being monitoring, with Hematology due to chronic idiopathic thrombocytopenia who progressed with abdominal pain, anemia and pleural effusion; a computed tomography scan of the abdomen was performed, showing a heterogeneous solid splenic mass. The patient underwent total videolaparoscopic splenectomy and progressed with improvement of abdominal pain and normalization of the platelet series, with no recurrence of pleural effusion after the procedure. The rarity and complexity of the case added to the diagnostic difficulty and therapeutic approach were factors that corroborated for the presentation of this case. (AU)


Subject(s)
Humans , Female , Aged , Splenic Neoplasms/diagnosis , Kasabach-Merritt Syndrome/diagnosis , Hemangioma/diagnosis , Oxygen Inhalation Therapy , Pleural Effusion/drug therapy , Pleural Effusion/diagnostic imaging , Spinal Puncture , Splenectomy , Splenomegaly/diagnostic imaging , Thrombocytopenia/diagnosis , Bone Diseases, Metabolic , Bone Marrow/pathology , Radiography , Tomography, X-Ray Computed , Abdominal Pain , Video-Assisted Surgery , Dyspepsia , Dyspnea , Thoracentesis , Piperacillin, Tazobactam Drug Combination/therapeutic use , Anemia , Anti-Bacterial Agents/therapeutic use
19.
Autops. Case Rep ; 9(1): e2018059, Jan.-Mar. 2019. ilus
Article in English | LILACS | ID: biblio-987013

ABSTRACT

An 84-year-old Japanese woman with myelodysplastic syndrome was admitted with pyrexia and dyspnea, but died suddenly during diagnostic evaluation. The autopsy revealed miliary tuberculosis in addition to myelodysplastic syndrome in the bone marrow. The immediate cause of the patient's sudden death was pulmonary fat embolism derived from bone marrow necrosis. This case shows that the infiltration of the myelodysplastic bone marrow by tuberculosis and consequent bone marrow necrosis and fat embolism can be the cause of sudden death. In this article, we report the autopsy results of this unusual cause of sudden death, and discuss tuberculosis-related sudden death with a review of the literature.


Subject(s)
Humans , Female , Aged, 80 and over , Tuberculosis/pathology , Death, Sudden/etiology , Embolism, Fat/complications , Autopsy , Bone Marrow/pathology , Fatal Outcome , Necrosis
20.
Rev. méd. Chile ; 147(3): 275-280, mar. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1004347

ABSTRACT

Background: Waldenström macroglobulinemia (WM) is an uncommon indolent B-cell lymphoma, due to the proliferation of lymphoplasmacytic cells, and secretion of a monoclonal IgM protein. Aim: To evaluate the clinical characteristics, management and results of treatment of patients with WM at a public hospital in Chile. Patients and Methods: Review of medical records of 31 patients aged 43 to 85 years (16 males) with WM diagnosed between 2002 and 2017. Clinical features and survival were recorded. Results: All patients had bone marrow compromise, and 31%, extranodal involvement. According to the International Prognostic Score System for WM (IPSSWM) 16, 58 and 26% were at low, intermediate and high risk, respectively. Twenty-five patients (81%) were treated, 32% with plasmapheresis and 36% with rituximab. Four cases (16%) achieved complete remission. Median follow up was 35 months (range 6-159). Estimated overall survival (OS) at 5 and 10 years was 74% and 53%, respectively. According to IPSSWM, the estimated five-year OS was 80, 92 and 39%, for low, intermediate and high-risk patients, respectively. Conclusions: OS was similar to that reported abroad, except for low risk patients, probably due to the low number of cases and short follow up. An improved survival should be expected with the routine use of immunochemotherapy.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Waldenstrom Macroglobulinemia/diagnosis , Vincristine , Biopsy , Bone Marrow/pathology , Prednisone/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chile/epidemiology , Survival Rate , Retrospective Studies , Treatment Outcome , Waldenstrom Macroglobulinemia/mortality , Waldenstrom Macroglobulinemia/drug therapy , Cyclophosphamide/therapeutic use , Rituximab/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use
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