Clinical features and prognostic factors of elderly patients with mantle cell lymphoma / 中华血液学杂志

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.

Clinical Features and Outcomes of the Patients with B-Cell Chronic Lymphoproliferative Disease in the New Drug Era / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of the patients with B-cell chronic lymphoproliferative disease（B-CLPD） in the new drug era and the effect of new drug treatment on efficacy and survival.@*METHODS@#The clinical and laboratory data of 200 cases B-CLPD patients diagnosed between April 2015 and August 2021 were analyzed retrospectively. The clinical efficacy and survival of the patients under different treatments including Bruton tyrosine kinase（BTK） inhibitors， rituximab， and chemotherapy alone were analyzed. The prognostic factors affecting the survival of patients were analyzed by univarite analysis and multivariate analysis.@*RESULTS@#There were 119 male（59.5％） and 81 female（40.5%） in 200 cases B-CLPD patients， the sex ratio(male/female) was 1.5∶1 with median age of 61（30- 91） years old. The distribution of subtypes were as fallows: 51 cases (25.5%) of chronic lymphocytic leukemia/small lymphocytic lymphoma（CLL/SLL）， 64（32.0%） cases of follicular lymphoma（FL）， 40（20.0%） cases mantle cell lymphoma（MCL）， 30（15.0%） cases of marginal zone lymphoma（MZL）， 10（5%） cases of lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia（LPL/WM）， 5（2.5%） cases of B cell chronic lymphoproliferative disorders unclassified（B-CLPD-U） . The main clinical manifestation of 102 patients was lymph node enlargement, 32 cases were complicated with B symptoms. Among CLL/SLL patients， there were 12（23.5%） cases in Binet A and 39（76.5%） cases in Binet B/C. There were 29 patients（20.9%） in Ann Arbor or Lugano stage I-II and 110 cases（79.1%） in stage III-IV of other subtypes. The complete remission（CR） rate was 43.1%（25/58）， 40.2%（39/97）， 7.1%（1/14）， and overaIl response rate（ORR） was 87.9%（51/58）， 62.9%（61/97）， 28.6%（4/14） in the groups of BTK inhibitors， rituximab-based therapy， and chemotherapy alone. The 3-year OS rate and PFS rate in all patients was 79.2% and 72.4% respectively. The 3-year OS rate of patient with MZL, CLL/SLL, FL,WM was 94.7%, 87.7%, 86.8% and 83.3% respectively, while the 3-year OS rate of MCL was only 40.6%, which was significantly lower than other subtypes. The median OS of patients treated with BTK inhibitors and rituximab-based therapy was 20.5 and 18.5 months respectively， and the 3-year OS rate was 97.4% and 90.7%. However， the median PFS of patients receiving chemotherapy alone was 4 months， and the 1-year OS rate was 52.7%， which was statistically significant compared with the other two groups（P<0.05）. Univarite analysis showed that anemia， elevated lactate dehydrogenase， elevated β2-microglobulin， and splenomegaly were the poor prognostic factors for OS（P<0.05）， elevated lactate dehydrogenase was also poor prognostic factors for PFS（P<0.05）. Multifactor analysis showed that anemia and elevated lactate dehydrogenase were the independent poor prognostic factors for survival（P<0.05）.@*CONCLUSION@#The clinical features of B-CLPD was various， anemia and elevated lactate dehydrogenase are the prognostic factors for poor survival. BTK inhibitors and new immunotherapy can improve the survival and prognosis of patients in the new drug era.

Lymphomatous Polyposis: Case Report and Literature Review / Poliposis linfomatosa: reporte de caso y revisión de la literatura

Abstract Lymphomatous polyposis (LP) is the endoscopic feature of primary gastrointestinal mantle cell lymphoma (MCL), a rare type of B-cell non-Hodgkin's lymphoma (NHL) and a typical but rare endoscopic pattern of gastrointestinal tract involvement (GIT) by nodal MCL. We present the case of a 62-year-old man with nodal MCL, with LP as a manifestation of GIT, and review the literature.

Resumen La poliposis linfomatosa (PL) es la característica endoscópica del linfoma de células del manto (LCM) gastrointestinal primario, un tipo infrecuente de linfoma no Hodgkin (LNH) de células B, así como un patrón endoscópico típico, pero infrecuente, del compromiso del tracto gastrointestinal (TGI) por LCM nodal. Presentamos el caso de un hombre de 62 años con LCM nodal, con PL como manifestación del compromiso gastrointestinal, y realizamos una revisión de la literatura.

Application of modified Matutes score containing CD200 in diagnosis of chronic lymphocytic leukemia / 中南大学学报(医学版)

OBJECTIVES@#Immunophenotyping technique is a powerful tool for the diagnosis and differential diagnosis of chronic lymphocytic leukemia (CLL) and other B-cell chronic lymphoproliferative diseases (B-CLPD). CD200 is strongly expressed in CLL. This study aims to analyze the clinical value of modified Matutes score (MMS) containing CD200 in the diagnosis of CLL.@*METHODS@#We retrospectively analyzed 103 B-CLPD patients diagnosed from January 2020 to July 2021, including 64 CLL patients, 11 follicular lymphoma (FL) patients, 14 mantle cell lymphoma (MCL) patients, 6 marginal zone lymphoma (MZL) patients, 1 hairy cell leukemia (HCL) patient, and 7 lymphoplasmic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) patients. The expression of CD markers between the CLL group and the non-CLL group was compared, and the sensitivity, specificity, and clinical consistency of MMS and Royal Marsden Hospital (RMH) immunophenotyping score system were analyzed.@*RESULTS@#There were significant differences in the expressions of CD5, CD23, FMC7, CD22, CD79b, CD200, and sIg between the CLL group and the non-CLL group (χ2 values were 37.42, 54.98, 30.71, 11.67, 55.26, 68.48, and 17.88, respectively, all P<0.01). When the RMH immunophenotyping score≥4, the sensitivity was 79.7%, and the specificity was 100%. When the MMS≥3, the sensitivity was 95.3%, and the specificity was 100%. The Kappa coefficient of RMH immunophenotyping system was 0.677, and the Kappa coefficient of MMS system was 0.860.@*CONCLUSIONS@#The MMS system containing CD200 has better sensitivity and same specificity compared with RMH immunophenotyping system, and MMS system may be more useful in the diagnosis of CLL.

Clinicopathological and molecular genetic features of cyclin D1-negative mantle cell lymphoma / 中华病理学杂志

Objective: To investigate the clinicopathological features and molecular genetics of cyclin D1-negative mantle cell lymphoma (MCL). Methods: The clinicopathological features and molecular genetics of CyclinD1-negative MCL diagnosed between January 2016 and July 2021 at the First Affiliated Hospital of Zhengzhou University were analyzed using immunohistochemistry and fluorescence in situ hybridization. Clinical information was collected and analyzed. Results: A total of five Cyclin D1-negative MCL cases from all 212 MCL patients (5/212, 2.4%)were included. There were three male and two female patients,age ranged from 59 to 70 years (median 64 years). All patients presented with nodal lesions. None of the patients had B symptoms but four had bone marrow involvement. Histopathologically, four cases were classic MCL and one case was pleomorphic variant type. All five cases were negative for Cyclin D1 but SOX-11 were positive in all cases. CD5 was positive in four cases and one case was weakly positive for CD23. CD10 and bcl-6 were negative in all cases. CCND1 translocation was identified in three cases and CCND2 translocation in one case by FISH analysis. However,CCND3 translocations were not found in the five cases. Conclusions: Cyclin D1-negative MCL are uncommon, its accurate diagnosis needs combined analysis with morphologic and immunophenotypic characteristics and genetic changes. It may be particularly difficult to distinguish from other small cell type B cell lymphomas. FISH analyses for CCND1/CCND2/CCND3 translocations and immunohistochemistry for SOX-11 are helpful to resolve such a difficult distinction.

Blastoid mantle cell lymphoma: cutaneous infiltration

Abstract Mantle cell lymphoma is an aggressive B-cell, non-Hodgkin's lymphoma, with lymph node or extranodal origin, and a mean survival of three to five years. Skin involvement is rare, secondary and indicates neoplasia dissemination. The authors report a case of a female patient, 69 years old, diagnosed previously, after lymph node and bone marrow biopsy. She was undergoing the second chemotherapy regimen when she showed infiltrated plaque-like lesions, nodules and tumors on the trunk and thigh root. Histopathology and immunohistochemistry demonstrated cutaneous infiltration of the blastoid lymphoma.

The Types and Laboratory Characteristics of Non-Hodgkin Lymphoma with Bone Marrow Invasion as the First Manifestation / 中国实验血液学杂志

OBJECTIVE@#To investigate the types and laboratory characteristics of non-Hodgkin lymphoma(NHL) with bone marrow invasion as the first manifestation.@*METHODS@#81 non-Hodgkin lymphoma patients with bone marrow invasion as the first manifestation treated in our hospital from January 2010 to July 2019 were selected. The clinical features, blood routine, lactate dehydrogenase (LDH), EB virus results, bone marrow features, immunophenotyping, gene and genetic characteristics of all patients were analyzed retrospectivel.@*RESULTS@#Among 81 patients, 73 cases(90%) were B-cell lymphoma, 5 cases(6%) were T-cell lymphoma and 3 cases(4%) were NK/T-cell lymphoma, while the mantle cell lymphoma and diffuse large B-cell lymphoma were the highest, which accounted for 21%(17 cases) and 19.7%(16 cases), and lymphoma accounted for 8.6%(7 cases). There were 44 cases(54.3%) showed B symptoms, 65 cases (80.2%) showed abnormal blood routine. The MYD88 gene was detected in 5 of 17 cases. 25 cases of patients underwent chromosome examination, the result showed that 5 cases were t(8; 14) (q24; q32), 3 cases were complex karyotype and 17 cases were normal karyotype. 23 cases(23.4%) were EB virus positive, 42 cases(51.9%) were LDH increased. The proportion of bone marrow lymphoma cells was 1%-92%. Among them, 32 cases were diagnosed as lymphoma leukemia, and 6 cases of bone marrow lymphoma cells showed mass distribution similar to extramedullary tumor cells with bone marrow metastasis.@*CONCLUSION@#B-cell lymphoma is the predominant NHL with bone marrow invasion as the first manifestation, while mantle cell lymphoma and diffuse large B-cell lymphoma are the most common pathological types with blood routine abnormalities. Bone marrow lymphoma cells can also present clusters of bone marrow metastasis, different types of lymphoma cells can make directional diagnosis.

Effect of RITA on TP53 Mutant Human Mantle Cell Lymphoma Cell Line and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of RITA on TP53 mutant human mantle cell lymphoma (MCL) cell line Mino and its possible mechanism.@*METHODS@#Mino cells were cultured in RPMI-1640 and treated with RITA at a concentration of 0-16 μmol/L for 24,48,72 hours. Cell viability was assessed by CCK-8 assay. The cells were treated by RITA (0-8 μmol/L) for 48 h, the cell apoptosis induced by RITA was detected by annexin V/PI flow cytometry. Western blot was performed to evaluate the expression of protein BCL-2, Caspase-3, Cleaved Caspase-3, PARP, MDM2, and P53 in Mino cells.@*RESULTS@#After treatment with 0.5, 1, 2, 4, 8, and 16 μmol/L RITA for 48 h, the proliferation inhibition rate of Mino cells was (1.2±5.6)%, (14.9±4.9)%, (41.7±5.0)%, (61.8±2.4)%, (70.2±2.8)%, and (70.8±2.4)%, respectively. RITA could inhibit the proliferation of Mino cells significantly, and statistical analysis showed that the inhibition rate was increased with the increasing of RITA concentration (r=0.767). After the cells were treated by 4 μmol/L RITA for 24, 48, and 72 h, the proliferation inhibition rate was (25.2±3.8)%, (61.8±2.4)%, and (87.0±0.7)%, respectively. Satistical analysis showed that the inhibition rate was also increased with the increasing of treatment time (r=0.978). The apoptosis rate of Mino cells treated by 0, 2, 4, and 8 μmol/L RITA for 48 h was (5.4±0.4)%, (15.3±0.6)%, (38.7±1.7)%, and (50.8±1.1)%, respectively, and it showed dose-dependent manner (r=0.961). Western blot showed that with the increasing of RITA concentration, the BCL-2 protein expression was decreased in a dose-dependent manner (r=0.932), moreover, PARP cleavage and Caspase-3 activation were found, while the protein expression of MDM2 and P53 showed no change.@*CONCLUSION@#RITA can inhibit the proliferation and induce the apoptosis of Mino cells significantly. The mechanism may be dependent on the Caspase pathway, but independent on the P53 pathway.

Mantle cell lymphoma presenting with lethal atraumatic splenic rupture

Mantle cell lymphoma is characterized by t(11;14) with CCND1-IGH fusion and manifests with a spectrum of disease ranging from relatively indolent to aggressive. Here, we present a case of pleomorphic mantle cell lymphoma with three fusion signals that presented with lethal atraumatic splenic rupture. We discuss on the implications of variant CCND1 signal patterns as well as the epidemiology and pathophysiology of atraumatic splenic rupture.

How to manage lymphoid malignancies during novel 2019 coronavirus (CoVid-19) outbreak: a Brazilian task force recommendation

ABSTRACT: The novel Coronavirus (CoVid-19) outbreak is now consider a world pandemic, affecting more than 1,300,000 people worldwide. Cancer patients are in risk for severe disease, including a higher risk of intensive care unit (ICU) admission, need for invasive ventilation or death. Management of patients with lymphoid malignancies can be challenging during the outbreak, due to need of multiple hospital visits and admissions, immunosuppression and need for chemotherapy, radiotherapy and stem cell transplantation. In this article, we will focus on the practical management of patients with lymphoid malignancies during the COVID-19 pandemic, focusing on minimizing the risk for patients.

Relationship of Expression of Circ_cgga162 with the Prognosis of Patients with Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of Circ_cgga162 in serum of mantle cell lymphoma (MCL) patients and analyze its potential as a prognostic biomarker.@*METHODS@#The expression of Circ_cgga162 in 86 cases of mantle cell lymphoma and 50 cases of lymph node reactive hyperplasia (RH) were detected by real-time quantitative polymerase chain reaction (qRT-PCR). The relationship between the expression of Circ_cgga162 and clinicopathological features was analyzed by univariate analysis. The relationship of Circ_cgga162 expression with progression-free survival time and overall survival time was analyzed by Kaplan-Meier. The relationship between expression of Circ_cgga162 and prognosis of patients was analyzed by univariate and multivariate analysis.@*RESULTS@#The expression level of Circ_cgga162 in MCL patients was significantly higher than that in control (RH) group (P＜0.01). The expression of Circ_cgga162 not correlated with age, gender, B symptoms and LDH (all P＞0.05), but correlated with the expression of MCL International Prognostic Index (IPI), Ann Arbor stage, bone marrow infiltration and Ki67 (all P＜0.05). In addition, Kaplan-Meier analysis showed that the progression-free survival time and overall survival time of the MCL patients with high expression of Circ_cgga162 were significantly shorter than those of the MCL patients with low expression (P＜0.01). Univariate analysis showed that Ann Arbor stage, Circ_cgga162 expression, MIPI, bone marrow infiltration and Ki67 were the prognostic factors for MCL patients (all P＜0.05). Multivariate Cox regression analysis showed that Ann Arbor stage, Circ_cgga162 expression and MIPI were independent factors affecting the prognosis of MCL patients (all P＜0.05).@*CONCLUSION@#Circ_cgga162 is highly expressed in serum of patients MCL, which relates with the prognosis of MCL patients. Circ_cgga162 can be used as a potential prognostic marker and therapeutic target for MCL patients.

Effects of Decitabine Combined with Bortezomib on the Proliferation of Mantle Cell Lymphoma Cell Lines and Its Underling Mechanisms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of decitabine combined with bortezomib on the proliferation of mantle cell lymphoma cell lines (Jeko-1 and Grante519) in vitro and explore the underlying mechanisms.@*METHODS@#Jeko-1 and Grante519 cells were treated with different concentrations of decitabine and/or bortezomib alone and their combination.The cell proliferation was determined by CCK-8 assay. the cell apoptosis were detected by flow cytometry, the mRNA and protein expression levels of genes related with the cell cycle and apoptosis were analyzed by RT-PCR and Western blot respactively.@*RESULTS@#Low dose DAC could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner. After DAC treatment, caspase 3, BAX and PCDH8 expression levels increased, while BCL-2 and CCND1 expression levels decreased in Jeko-1 and Grante519 cells, but there was no significant difference in NF-κB expression. High dose BTZ could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner; single drug BTZ could increase the expression level of Caspase 3 and BAX, and decrease the expression level of NF-κB, BCL-2 and CCDN1 in Jeko-1 and Grante519 cells, but there was significant difference in PCDH8 expression level. Compared with single-drug treatment group, DAC combined with BTZ significantly increased the inhibitory rate and apoptotic rate of Jeko-1 and Grante519 cells; PCDH8, Caspase 3 and BAX expression levels significantly increased, and the expression levels of NF-κB, BCL-2 and CCND1 significantly decreased in Jeko-1 and Grante519 cells.@*CONCLUSION@#The combination of DAC and BTZ has obviously synergistic effects on the growth inhibition of Jeko-1 and Grante519 cells which maybe relates with enhancing inbibitory effect on NF-κB signal pathway, down-regulating BAX expression, up-regulating BAX expression as well as increasing cospase 3 expression. This study provides a novel therapeutic approach for mantle cell lymphoma.

Mantle cell lymphoma relapsed after autologous stem cell transplantation: a single-center experience

BACKGROUND: Autologous stem cell transplantation (autoSCT) can extend remission of mantle cell lymphoma (MCL), but the management of subsequent relapse is challenging.METHODS: We examined consecutive patients with MCL who underwent autoSCT at Veterans Affairs Puget Sound Health Care System between 2009 and 2017 (N=37).RESULTS: Ten patients experienced disease progression after autoSCT and were included in this analysis. Median progression free survival after autoSCT was 1.8 years (range, 0.3–7.1) and median overall survival after progression was only 0.7 years (range, 0.1 to not reached). The 3 patients who survived more than 1 year after progression were treated with ibrutinib.CONCLUSION: Our findings suggest that ibrutinib can achieve relatively prolonged control of MCL progressing after autoSCT.

Chimeric antigen receptor T-cell therapy: a promising treatment modality for relapsed/refractory mantle cell lymphoma / 医学前沿

Mantle cell lymphoma (MCL) is a distinct histological type of B-cell lymphoma with a poor prognosis. Several agents, such as proteasome inhibitors, immunomodulatory drugs, and inhibitors of B cell lymphoma-2 and Bruton's tyrosine kinase have shown efficacy for relapsed or refractory (r/r) MCL but often have short-term responses. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel treatment modality for r/r non-Hodgkin's lymphoma. However, long-term safety and tolerability associated with CAR T-cell therapy are not defined well, especially in MCL. In this report, we described a 70-year-old patient with r/r MCL with 48-month duration of follow-up who achieved long-term remission after CAR T-cell therapy. CAR T-cell-related toxicities were also mild and tolerated well even in this elderly patient. This report suggested that CAR T-cell therapy is a promising treatment modality for patients with MCL, who are generally elderly and have comorbid conditions.

Angiogênese e prognóstico em linfoma de células do manto / Angiogenesis and prognosis in mantle cell lymphoma

INTRODUÇÃO: Fatores prognósticos em Linfoma de Células do Manto (LCM) foram definidos em época sem padronização de tratamento e menos conhecimento de patogenia. Entre estes conhecimentos a participação da angiogênese ainda tem sido pouco estudada. Assim, a identificação de novos fatores prognósticos e melhor definição do impacto da angiogênese no LCM podem auxiliar na terapêutica e caracterizar grupos com maior risco de óbito. OBJETIVO: Avaliar a microdensidade vascular (MDV) em pacientes com LCM tratados no A.C.Camargo Cancer Center e relacioná-la a fatores que impactem na sobrevida global(SG). MATERIAL E MÉTODOS: Estudo retrospectivo, unicêntrico, transversal em portadores de LCM não indolente em cujas amostras histológicas foi quantificada MDV através de CD34 e avaliada angiogênese através de HIF-∝ e VEGF. Também foram consideradas variáveis demográficas, clínicas, laboratoriais, índices prognósticos e dados de tratamento e resposta ao tratamento. Modelo de riscos proporcionais de Cox simples foi ajustado para descrever a relação entre variáveis independentes e tempo até o óbito. Seleção das variáveis para modelo de regressão de Cox múltiplo foi considerada a partir dos resultados do modelo de Cox simples. RESULTADOS: No período de 2006 a 2014 analisamos 63 pacientes. A maioria foi do sexo masculino (68.3%) com estádio IV (81%). A mediana de idade foi de 64 anos e mediana de MIPI e MIPI-b de 5,7 e 6,2 respectivamente. Citarabina em alta dose foi utilizada em 44,4% dos pacientes e 36,5 % dos pacientes realizaram TACTH. O tempo mediano de seguimento foi 72,34 meses e a mediana de sobrevida global (SG) foi de 93,91 meses. Dos 63 pacientes iniciais, 34 dispunham de amostras para análise de MDV. A média e mediana de MDV foi de 14,88 e 3,5 vasos/mm2 respectivamente e 64,71% dos pacientes apresentaram VEGF e HIF-∝ ≥10%. Em análise univariada nenhum parâmetro de angiogenese apresentou significância estatística. Idade, hemoglobina , albumina, número de leucócitos, linfócitos, plaquetas, valores de MIPI e Ki-67 apresentaram significância estatística para SG. Em análise multivariada idade, concentração de albumina e plaquetas apresentaram significância permitindo estabelecer que pacientes com idade superior a 70 anos possuíram risco 8 vezes maior (HR=8,025; valor p=0,0101) de ir à óbito em relação aqueles com idade menor ou igual a 70 anos. Para cada incremento de unidade de albumina houve redução de 79,9% (HR=0,201; valor p=0,005) no risco de óbito mantido a idade constante enquanto pacientes com contagem de plaquetas acima de 146x109/l tiveram redução de risco de óbito em 78% (HR=0,231; valor p=0,003). CONCLUSÃO: Os resultados do presente estudo permitem concluir que a angiogênese não demonstrou ser um valor preditivo de óbito e que parâmetros diferentes dos habitualmente utilizados associam-se a maior risco de óbito. Tais achados devem ser validados em uma coorte mais ampla de pacientes.

INTRODUCTION: Mantle Cell Lymphoma (MCL) prognostic factors were defined in a no standardized treatment and less well-known pathogenesis time. Among them, angiogenesis has been little studied. Therefore, angiogenesis impact better definition and new prognostic factors can define higher death-risk groups and help MCL patients' management. PURPOSE: To evaluate microvascular density (MDV) in MCL patients treated at the AC Camargo Cancer Center as well as identify demographic, clinical and laboratory factors that impact on overall survival (OS). MATERIAL AND METHODS: We conducted a retrospective, single-center and cross-sectional study. We included all non-indolent MCL patients who underwent immuno-chemotherapy. MDV was quantified by CD34 analysis and angiogenesis was determined by HIF-∝ and VEGF markers. We took into account demographic, clinical, laboratory, prognostic indexes, treatment and response to treatment variables. Cox's proportional hazards model was adjusted to data to describe variables and time until death relationship. Variables selection for multiple Cox regression analysis model was considered from simple Cox model results. RESULTS: From 2006 to 2014, we analyzed 63 patients. The majority were male (68.3%) and Ann Arbor stage IV (81%) and they were 64 years old median age with median MIPI= 5.7 and MIPI-b= 6.2. High dose cytarabine was used in 44.4% of patients and 36.5% underwent TACTH. Median follow-up was 72.34 months and median overall OS was 93.91 months. Of 63 patients, 34 had samples for MDV analysis. The mean and median MDV was 14.88 and 3.5 vessels / mm2, respectively and 64.71% of patients had VEGF and HIF-∝ ≥10%. In univariate analysis, no angiogenesis parameter showed statistical significance. Age, hemoglobin, albumin, leukocytes, lymphocytes, platelets, MIPI and Ki-67 values were statistically significant for overall survival. In multivariate analysis, age, albumin concentration and platelet count were statistically significant, allowing the establishment of a predictive model. Patients over 70 years old had more than 8 times increased death-risk (HR = 8.025; p = 0.0101) in relation to those with less than or equal to 70 years old. For each albumin unit increment a reduction of 79.9% (HR = 0.201; p-value = 0.005) is expected in death-risk while patients with platelet count above 146 x 109/l had a 78% reduction in death-risk in relation to those with platelet count equal to or less than this value (HR = 0.231; p-value = 0.003). CONCLUSION: Angiogenesis has not been shown to have death predictive value. Diferent parameters from those commonly used are associated with higher death-risk. Such findings should be validated in a broader cohort of patients.

Expression of MiR101 and EZH2 in Patients with Mantle Cell Lymphoma and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of miR-101 and EZH2 in patients with mantle cell lymphoma(MCL) and to analyze its correlation with clinical prognosis of MCL patients.@*METHODS@#RQ-PCR and S-P immunohistochemistry were used to detect the expressions of miR-101 and EZH2 in tissue of MCL patients. CCK-8 was used to assay the effect of miR-100 minics on the proliferation of Jeko-1 and Mino cells; the flow cytometry with Annexin V/PI double staining was used to assay the apoptosis; Western blot was used to assay the effect of miR-101 minics on the expression of EZH2 protein in Jeko-1 and Mino cells.@*RESULTS@#Compared with control group, miR-101 lowly expressed, and EZH2 protein highly expressed in MCL group, with very statistically significant difference(P<0.01).There was negative correlation between miR-101 and EZH2 expression(r=-0.638，P<0.05). The expression of miR-101 and EZH2 significantly correlated with B symptoms, International Prognostic Index(IPI) and Ann Arbor stage, respectively. Survival analysis showed that the overall survival(OS) rate of patients with low expression of miR-101 were significantly lower than that of patients with high miR-101 expression (P=0.0014), the OS rate of patients with EZH2 high expression were significantly lower than that of patients with EZH2 low expression (P=0.0093). The miR-100 minics could inhibit the proliferation of Jeko-1 and Mino cells, and increase the apoptotic rate. The expression of EZH2 protein was markedly suppressed by the miR-100 minics.@*CONCLUSION@#The expression of miR-101 and EZH2 is different in MCL patients with different clinical stage and prognosis. The miR-101 can inhibit the cell proliferation and induce cell apoptosis of mantle cell lymphoma by targeting EZH2.

Effect of Carfilzomib on Proliferation and Apoptosis of Mantle Cell Lymphoma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of Carfilzomib on mantle cell lymphoma (MCL), and to compare with effect of Bortezomib.@*METHODS@#The Jeko-1 cells and primary MCL cells were treated with Carfilzomib for 24, 48 and 72 h, then the inhibitory rate was detected using CCK-8. Lymphocytes derived from healthy volunteer were served as cell controls. Bortezomib and Cyclophosphamide (CTX) were served as medicinal controls. At the same time, the apoptosis of cells treated with different drugs was detected using flow cytometry.@*RESULTS@#The inhibitory effect of Carfilzomib on Jeko-1 cells and primary MCL cells was exhibited with time-dependent and concentration-dependent manners (P＜0.01, r=0.393, r=0.650, rJ=0.473, r=0.417), but the effect on lymphocytes derived from healthy volunteer only showed time-dependence (P＜0.01, r=0.928). Under the same concentration, Carfilzomib exhibited the proliferation Jeko-1 cells stronger than Bortezomib (P＜0.01), but the same inhibition on primary MCL cells was not significantly different from that on lymphocytes derived from healthy volunteer (P＞0.05). Under clinical recommended concentration, Carfilzomib had a stronger inhibitory effect on primary MCL cells than that of Bortezomib (P＜0.01). Cell apoptosis assay showed that under the same concentration the ability of Carfilzomib to induce cell apoptosis was significantly stronger than that of Bortezomib (P＜0.05).@*CONCLUSION@#Carfilzomib can inhibit the growth of MCL cells, its inhibitory rate on the MCL cells is higher than that of Bortezomib.

PLK1 Expression in Mantle Cell Lymphoma and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To explore the expression level of PLK1 in mantle cell lymphoma(MCL), and the effect of silencing PLK1 gene by RNA interference on the cell proliferation, apoptosis, and cell cycle.@*METHODS@#S-P immunohistochemistry technique was used to detect the expression of PLK1 in tissues of 42 patients with MCL and 30 patients with reactive proliferative lymphodenitis(RPL), their expression levels were compared and analyzed. The Jeko-1 cells were transfected with lentivirus contaiming PLK-1 shRNA, then the mRNA and protein expression of PLK-1 was detected by real-time guantitative PCR and Western blot nespectively, and the silencing efficacy of PLK-1 shRNA was identificd. The cell proliferation was detected by CCK method, the cell apoptosis was detected by Annexin V/PI double staining, the cell cycle was detected by PI single staining, the changes of apoptosis-related proteins BAX, BCL-2 and Caspase 3 were detected by Western blot.@*RESULTS@#The positive expression rate of PLK-1 in tissue of MCL patients was 66.67%(28/42), which was significanfly higher than 20%(6/30) in tissue of RPL patients (P＜0.05). The PLK-1 positive expression correlated with B symptom, IPI score, Ann-Arbor stage(P＜0.05). After infection of Jeko-1 cells with lentivirus containing PLK-1 shRNA for 72 hours, the mRNA and protein expressions of PLK-1 were significantly down-regulated(P＜0.05), the proliferation rate of cells in group of PLK-1 shRNA was significanly lower than that in control and Neg shRNA groups(P＜0.05); the apoptosis rate of cells in PLK-1 shRNA group was (27.42±3.44)%, which was significantly higher than that in control group (1.23±0.42)% and Neg shRNA group (2.07±0.58) % (P＜0.05). The cell cycle analysis showed that the cell ratio in G/M phase of PLK-1 shRNA group was (27.21±3.59) %, which was higher than that in control group (13.28±2.63)% and Neg shRNA group (14.34±2.37) %. The detection of apoptosis-related proteins showed that the expression of BAX was up-regulated, the expression of BCL-2 was down-regnlated and the expression of caspase 3 was up-regulated.@*CONCLUSION@#The PLK-l overexpression appears in tissue of MCL patients. The silencing PLK-1 gene can inhibit the proliferation of Jeko-1 cells, induce the apopotosis of Jeko-1 cells and arrestes cell cycle in G/M phase.