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Sinusoidal obstruction syndrome, previously known as veno-occlusive disease (VOD/SOS), is a complication in patients undergoing haemopoietic stem cell transplantation (HSCT). Severe VOD/SOS, including progression to multi-organ failure, has resulted in a mortality of greater than 80%. Defibrotide’s varying pharmacological actions, particularly on endothelial cells, make it is a useful agent to consider for prophylaxis and treatment of VOD/SOS. Barriers to its routine use include the high acquisition cost and the fact that neither the oral or parenteral formulations are licensed products in many countries at this time. This review summarises available literature on the use of defibrotide in the management of VOD/SOS. Publications consist predominantly of single centre cohort studies and case series. Available evidence indicates that defibrotide is effective in the management of VOD/SOS. Using defibrotide prophylaxis should also be considered, especially in the paediatric setting, where there are available results from a large, open label, randomized controlled trial. Patient outcome data from the larger studies and compassionate programs can inform consensus recommendations on dosing regimen and criteria for the treatment of VOD/SOS with defibrotide in the adult population. The reviewed literature indicates an effective and safe dose for treatment is 25 mg/kg/day, continued for at least 14 days or until complete response is achieved. Further studies are required to determine the optimal dose and duration of treatment in both paediatric patients and adults. Recent recommendations and a phase 3 trial using historical controls indicate that defibrotide should be included as a pharmacotherapy option in protocols guiding management of VOD/SOS. 相似文献
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M. Kashif Ishaqi A. Jamil M. Khanani M. Baroudi Omar Trad M. El-Hayek Eric Bouffet 《Journal of neuro-oncology》2010,98(1):137-141
Hepatic Sinusoidal Obstruction Syndrome (HSOS), the new name given to veno-occlusive disease (VOD) of the liver, is a well-known
complication of high-dose chemotherapy employed with hematopoietic stem cell transplantation, but it has rarely been observed
in children who receive conventional chemotherapy. HSOS following standard chemotherapy has been reported in patients receiving
vincristine, actinomycin D, and cyclophosphamide for the treatment of Wilms tumor and more rarely rhabdomyosarcoma. We report
a 14-year-old boy with high risk medulloblastoma treated with craniospinal radiation followed by chemotherapy, who experienced
severe HSOS after only one course of chemotherapy including carboplatin, vincristine, and cyclophosphamide. To our knowledge,
this is the second report of HSOS after standard dose chemotherapy for brain tumor in childhood. 相似文献
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目的:探讨梭形细胞变异型弥漫性大B细胞淋巴瘤的临床病理特征、病变性质及鉴别诊断要点。方法:对1例梭形细胞变异型弥漫性大B细胞淋巴瘤的组织形态特征、免疫组化表型,结合临床预后进行分析。结果:1例23岁女性患者在半年内先后发生结肠肿瘤和乳腺肿瘤。HE切片显示肿瘤细胞弥漫性浸润肠壁和乳腺组织,瘤细胞有异型性和核分裂,并伴有显著的梭形细胞特征。免疫表型显示瘤细胞CD45 ,CD20 ,CD45RO-,CD30-,Vim ,Des-,SMA-,S-100-,CK-,EMA-。患者1年内死于肿瘤。结论:本例梭形细胞变异型大B细胞淋巴瘤是一种罕见的高度恶性肿瘤,在缺乏免疫组化标记的情况下易误诊为肉瘤或低分化癌。 相似文献
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Huang JZ Weisenburger DD Vose JM Greiner TC Aoun P Chan WC Lynch JC Bierman PJ Armitage JO;Nebraska Lymphoma Study Group 《Leukemia & lymphoma》2003,44(11):1903-1910
We sought to investigate the clinical characteristics and pathologic features and survival outcome of patients with diffuse large B-cell lymphoma (DLBCL) arising in nodular lymphocyte predominant Hodgkin's disease (NLPHL), since controversy regarding their prognosis exists in the literature. Twenty-one patients with DLBCL arising either concurrently with (n=7) or subsequent to (n=14) a diagnosis of NLPHL were identified in the Nebraska Lymphoma Study Group Registry. The clinical and pathologic features of the cases were evaluated, and survival analysis was performed from the time of diagnosis of DLBCL. The median time to the development of DLBCL in those with prior NLPHL was only one year (range, 0.5-24 years). The median age of the patients at the time of diagnosis of DLBCL was 46 years (range, 18-72 years) and the male to female ratio was 17:4. Ten patients presented with nodal DLBCL only, six patients presented with both nodal and extranodal involvement, and five patients presented with only extranodal DLBCL. Eleven patients had limited stage (I/II) disease and 10 had advanced stage (III/IV) disease. The median overall survival (OS) and failure-free survival (FFS) of the entire group was 35 months and 11 months, respectively, and the predicted five-year OS and FFS was 31 and 18%, respectively. There were no significant differences in the survival outcomes between patients with DLBCL arising in NLPHL and age- and sex- matched patients with de novo DLBCL. In conclusion, our findings suggest that patients with DLBCL arising in NLPHL have a prognosis similar to those with de novo DLBCL and should be treated aggressively. 相似文献
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Papadaki HA Xylouri I Katrinakis G Foudoulakis A Kritikos HD Stathopoulos EN Boumpas DT Eliopoulos GD 《Leukemia & lymphoma》2003,44(2):275-279
Two cases of non-Hodgkin's lymphoma (NHL) associated with systemic lupus erythematosus (SLE) are described. Patient-1 was a 65-year-old woman in whom SLE and diffuse large B-cell lymphoma were concurrently diagnosed. The patient presented with low-grade fever, butterfly rash, arthritis and generalized lymphadenopathy without splenomegaly or bone marrow involvement. Complete remission of NHL and SLE was achieved with cyclophosphamide, adriamycin, vincristine and prednisone. Patient-2 was a 56-year-old woman in whom SLE had been diagnosed 14 years earlier. The patient presented with low-grade fever, bulky splenomegaly without lymphadenopathy, IgM λparaproteinemia, and expansion of a monoclonal CD19 + /CD22 + λ-type B-cell population in both bone marrow and peripheral blood. Diagnosis of a lympho-plasmacytoid lymphoma was established histologically after splenectomy. A partial remission of the neoplasm was achieved with cyclophosphamide, vincristine and prednisone. We suggest that the development of NHLs in patients with SLE may not be coincidental and we recommend the search for NHL in cases of SLE with prominent lymphadenopathy, massive splenomegaly or expansion of a monoclonal CD19 + /CD22 + B-cell population. 相似文献
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Krol AD le Cessie S Snijder S Kluin-Nelemans JC Kluin PM Noordijk EM 《Leukemia & lymphoma》2003,44(3):451-458
The Comprehensive Cancer Centre West (CCCW) population based non-Hodgkin's lymphoma (NHL) registry contains information on all newly diagnosed NHL patients living in the region covered by the CCCW. Patients were entered from June 1st 1981 to December 31st 1989. Follow-up is still ongoing, median follow-up is 113 months (1-191 months) for patients alive. In this study, patient and tumor characteristics, data on patterns of care, response and (relative) survival are described. As follicular lymphomas and diffuse large B-cell lymphomas are the most frequently occurring NHL subtypes in the database, a separate analysis is performed to characterize the clinical picture of these disease entities in the CCCW population. Our data illustrate that NHL patients in the general population are substantially older than patients included in trials and hospital based series. Due to older age, treatment is withheld or adapted for a substantial number of patients. The resulting survival and relative survival rates are a reflection of these choices. 相似文献
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Hawk Kim Kyoo-Hyung Lee Sang Kyun Sohn Chul Won Jung Young Don Joo Sung Hyun Kim Byung Soo Kim Jung Hye Choi Jae-Yong Kwak Min Kyoung Kim Sung Hwa Bae Ho-Jin Shin Jong Ho Won Sukjoong Oh Won Sik Lee Jae-Hoo Park Sung-Soo Yoon 《Leukemia research》2013
We retrospectively investigated the incidence, risk factors, and outcomes of SOS (sinusoidal obstruction syndrome; previously veno-occlusive disease [VOD]) after allogeneic hematopoietic stem cell transplantation (alloHSCT) in aplastic anemia. Two hundred and sixty patients were included in the analysis. SOS developed in 7.3% (n = 19/260) of patients. Classical Cy (200 mg/m2)-ATG was the most common conditioning regimen (84.2%) in the SOS group. The SOS mortality rate was 4/19 (21.1%). Univariate analyses revealed that Cy 200 mg/m2 conditioning (p = 0.035), classical Cy-ATG conditioning (p = 0.007), and horse ATG conditioning (p < 0.001) were significant risk factors for developing SOS. Multivariate analysis revealed that only horse ATG conditioning was a poor prognostic factor (HR = 3.484; 95% CI 1.226–9.904; p = 0.002). Rabbit ATG (HR 12.719; 95% CI 2.332–69.373; p = 0.003) and weight gain > 10% (HR 35.655; 95% CI 2.208–575.805; p = 0.012) were risk factors in the overall SOS group. Both rabbit ATG conditioning and weight gain of more than 10% were associated with poor overall survival with a median of 1.2 months (5Y survival rate, any risk factor vs. none: 74.6% vs. 0.0%; p < 0.001; Fig. 2) in the SOS group. 相似文献
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目的 探讨诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)在弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)组织中的表达及临床意义。方法 用免疫组化法检测40例DLBCL及15例反应性增生淋巴结中iNOS的表达情况,分析iNOS的表达与DLBCL患者性别、年龄、临床分期、国际预后指数(IPI)之间的关系。结果 iNOS在DLBCL及反应性增生淋巴结组织中的阳性表达率分别为67.5%、26.7%,两者比较差异有统计学意义(P<0.05)。iNOS的表达水平与临床分期、IPI有关(P<0.05),与患者性别、年龄无关(P>0.05)。结论 iNOS在DLBCL组织中有较高的阳性表达,其表达水平与患者的临床分期及IPI相关,提示iNOS在DLBCL的发生、发展过程中起重要作用。 相似文献
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The Frequency of Double Expresser in Selected Cases of High Grade Diffuse Large B-Cell Lymphomas
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Maria NaseemMuhammad AsifMuhammad Tahir KhadimHafeez Ud-DinShahid JamalIman Shoaib 《Asian Pacific journal of cancer prevention》2020,21(4):1103-1107
Background: Diffuse large B-cell lymphomas (DLBCL) are fast-growing non-Hodgkin lymphomas that affect B-lymphocytes. Double expressor DLBCL is the concomitant expression of Myc and Bcl-2 proteins during lymphomas which results in poor prognosis of patients. This study aimed to determine the frequency of double expresser in high grade diffuse large B-cell lymphomas. Materials and Methods : The study was conducted on 74 cases (54 males (68.4%) and 20 females (25.3%)) of DLBCL between August 2018 to January 2019. The mean age of the 74 patients was 51.7 years + 18.5. Expression of proteins c-Myc, Bcl-2 and Bcl-6 were evaluated by immunohistochemistry. The involvement of primary lymph node was reported in 38 cases (51.3%) whereas, extra nodal site was observed in 22 cases (29.7%). Among the primary sites, the cervical lymph node enlargement was the most frequent site of presentation. Results: The rearrangement pattern was studied among 74 patients, 35 (47%) were found to have either one of the rearrangements i.e. Myc, Bcl-2, or Bcl-6. On the other hand, 14 (18.9%) had shown double rearrangements i.e. Bcl-2 and c-Myc (11 cases) and Bcl-6 and c-Myc (3 cases). The Bcl-2 and Bcl-6 rearrangements were demonstrated by 12 cases whereas 2 cases (2.7%) indicated all three types of rearrangements i.e. c-Myc, Bcl-2, and Bcl-6. In 11 cases the Bcl-2 and c-Myc rearrangements were found to be Bcl-2 > 50% and c-Myc > 40% and demonstrating the overall frequency of double expressers as 14.8%. The prognosis of the mentioned cases was extremely poor, median survival of 10 months. Conclusion: The concurrent expression of Bcl-2 and c-Myc was found to be 14% (level of expression for Bcl-2 > 50% and c-Myc > 40%) which is potentially a significant health burden and an emerging threat. 相似文献
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Christian Marinaccio Giuseppe Ingravallo Francesco Gaudio Tommasina Perrone Beatrice Nico Eugenio Maoirano Giorgina Specchia Domenico Ribatti 《Leukemia research》2014
Diffuse Large B-cell Lymphoma (DLBCL) is the most common form of Non-Hodgkin lymphoma characterized by clinical and biological heterogeneity attributable both to the tumor cells and the complex tumor-microenvironment surrounding them. Tumor-associated macrophages (TAMs) and mast cells are two major components of the tumor inflammatory infiltrate with a definite role in enhancing tumor angiogenesis. In this study, we have investigated CD68 and tryptase expression and their relationship with microvascular density (MVD) in chemo-resistant and chemosensitive patients affected by DLBCL. CD68 and tryptase expression as well as MVD were increased in chemo-resistant patients when compared with chemosensitive patients. Tryptase expression showed a positive correlation with MVD, supporting a role for mast cell in DLBCL tumor angiogenesis, while CD68 correlation with MVD was not significant, indicating a different role for TAMs than angiogenesis in DLBCL. 相似文献
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Junya Yoneda Ikuo Saiki Hideo Kobayashi Hideki Fujii Yukuo Ishizaki Ikunoshin Kato Makoto Kiso Akira Hasegawa Ichiro Azuma 《Cancer science》1994,85(7):723-734
We have investigated the inhibitory mechanism of the initial arrest of L5178Y-ML25 lymphoma cells in a target organ (liver) by using recombinant fibronectin fragments with cell- and/or heparin-binding domains (C-274, H-271 or the fusion fragment CH-271). Pretreatment of hepatic sinusoidal endothelial (HSE) cell monolayers with lymphoma cells or their conditioned medium for 4 to 6 h resulted in the enhancement of lymphoma cell adhesion to HSE cell monolayer. The increased tumor adhesiveness was completely abolished by preincubation of the conditioned medium with anti interleukin-1β monoclonal antibody (mAb). Synthetic sialyl Lex (SLex ) as a ligand for endothelial cell leukocyte adhesion molecule-1 (ELAM-1) adhesion receptor and anti ELAM-1 mAb blocked the conditioned medium-induced enhancement of tumor-endothelial cell interaction, while pretreatment of the activated HSE cell monolayer with anti vascular cell adhesion molecule-1 (VCAM-1) mAb did not affect the enhanced tumor cell adhesion. These results indicate that tumor cell interaction with the stimulated HSE cells is mediated by ELAM-1 molecules on HSE cells. However, the expression of SLex and SLea on the tumor surface was not observed by flow cytometric analysis. ELAM-1-mediated enhancement of tumor cell adhesion to HSE monolayer was also inhibited in a concentration-dependent manner by CH-271 fusion polypeptide or the sulfated chitin derivative sulfated carboxyntethyl-chitin, which can bind to the heparin-binding domain of CH-271. In addition, CH-271 inhibited not only tumor-endothelium interaction hut also tumor cell invasion into reconstituted basement membrane Matrigel in vitro . 相似文献
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Enrico Derenzini Claudio Agostinelli Enrica Imbrogno Ilaria Iacobucci Beatrice Casadei Elisa Brighenti Simona Righi Fabio Fuligni Andrea Ghelli Luserna Di Rorà Anna Ferrari Giovanni Martinelli Stefano Pileri Pier Luigi Zinzani 《Oncotarget》2015,6(9):6553-6569
The recent finding that MYC-driven cancers are sensitive to inhibition of the DNA damage response (DDR) pathway, prompted us to investigate the role of DDR pathway as therapeutic target in diffuse large B-cell lymphoma (DLBCL), which frequently overexpresses the MYC oncogene. In a preliminary immunohistochemical study conducted on 99 consecutive DLBCL patients, we found that about half of DLBCLs showed constitutive expression of the phosphorylated forms of checkpoint kinases (CHK) and CDC25c, markers of DDR activation, and of phosphorylated histone H2AX (γH2AX), marker of DNA damage and genomic instability. Constitutive γH2AX expression correlated with c-MYC levels and DDR activation, and defined a subset of tumors characterised by poor outcome. Next, we used the CHK inhibitor PF-0477736 as a tool to investigate whether the inhibition of the DDR pathway might represent a novel therapeutic approach in DLBCL. Submicromolar concentrations of PF-0477736 hindered proliferation in DLBCL cell lines with activated DDR pathway. These results were fully recapitulated with a different CHK inhibitor (AZD-7762). Inhibition of checkpoint kinases induced rapid DNA damage accumulation and apoptosis in DLBCL cell lines and primary cells. These data suggest that pharmacologic inhibition of DDR through targeting of CHK kinases may represent a novel therapeutic strategy in DLBCL. 相似文献
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目的 探讨放疗在早期弥漫大B细胞淋巴瘤(DLBCL)化疗后达CR患者中的地位。方法 回顾分析2004—2012年本院治疗的376例Ⅰ、Ⅱ期DLBCL患者资料,均接受至少3个周期CHOP和利妥昔单抗+CHOP方案化疗(R-CHOP)后达CR者。R-CHOP组92例,R-CHOP+放疗组79例,CHOP+放疗组98例,CHOP组107例。放疗为累及野照射30~56 Gy。Kaplan-Meier法计算生存率并Logrank法检验,Cox回归模型多因素预后分析。结果 5年样本量为188例。全组5年DFS、OS分别为80.7%、87.6%,R-CHOP+放疗组和R-CHOP组的分别为94.9%和88.1%(P=0.030)、97.9%和86.0%(P=0.026),CHOP+放疗组和CHOP组的分别为74.2%和71.4%(P=0.623)、87.0%和82.1%(P=0.420)。多因素分析显示吸烟指数<500、IPI<2、加用利妥昔单抗是预后有利因素(P=0.034~0.000)。结论 放疗对早期DLBCL可以提高R-CHOP化疗后CR者的DFS和OS。建议DLBCL使用含利妥昔单抗的化疗,R-CHOP化疗后应接受放疗。希望开展随机对照研究进一步证明该结果。 相似文献
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Spontaneous regression of an anaplastic large cell lymphoma in the oral cavity: first reported case and review of the literature 总被引:2,自引:0,他引:2
Lymphomas account for 2–5% of all oral malignancies and are the third most common in this site. This case report appears to be the first in the world literature describing spontaneous regression in the oral cavity of a subset of non-Hodgkins lymphomas known as Ki-1 anaplastic large cell lymphomas (ALCL). Ki-1 ALCL account for 2–7% of all non-Hodgkins lymphomas and the clinical presentation is variable; they may arise de novo or in the setting of a separate primary lymphoma and commonly present in the extra-nodal location. Disease severity is also variable with waxing and waning lesions at one extreme which may spontaneously regress to bone marrow involvement in around 12% of cases. This case is especially interesting since the patient is a farmer, given the recent evidence that there may be a link between non-Hodgkins lymphoma and this occupation. 相似文献
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背景与目的:弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)根据基因表达可以分成有两种不同预后的亚型:生发中心B细胞样亚型(germinal centre B-cell lymphoma,GCB)和活化B细胞样亚型(non-germinal centre B-cell lymphoma,non-GCB).本文分析原发于淋巴结内DLBCL的临床特征、免疫亚型及预后,并探讨有效的治疗方法.方法:收集本院2003年-2009年诊治的70例结内DLBCL.分析其临床资料和IPI评分,用免疫组织化学染色分成GCB和non-GCB两类免疫亚型.治疗方法包括CHOP化疗及利妥昔单抗联合CHOP (R-CHOP)免疫化疗.用Kaplan-Meier法、log-rank检验和Cox回归模型对其临床资料、免疫亚型和治疗结果进行生存分析及单因素和多因素预后分析.结果:全组患者的5年生存期(overall survival,OS)为67.8%.其中CHOP化疗患者的5年OS为58.9%,R-CHOP免疫化疗患者为77.2%,免疫化疗明显优于单纯化疗(P=O.017).免疫亚型为GCB型患者5年OS为73%,non-GCB型患者为55.9%,两者差异无统计学意义(P=0.13).但进一步分析:用CHOP化疗的non-GCB型患者5年OS明显低于GCB型患者(43.5% vs 66.8%,P=0.042);而用R-CHOP免疫化疗的non-GCB型患者5年OS与GCB型患者差异无统计学意义(67.5% vs 80.4%,P=0.717).在nonGCB亚型中,R-CHOP免疫化疗5年OS明显优于CHOP化疗(73.3% vs 42.9%,P=0.02),提示R-CHOP免疫化疗能明显延长non-GCB亚型患者的长期生存.各临床因素与OS的关系:单因素分析表明年龄≥60岁、Ⅲ期、血清LDH升高、B症状和IPI≥3分均是预后不良的因素(P<0.05).Cox多因素回归模型分析结果显示,IPI评分对OS的影响有统计学意义(P<0.01),是独立的预后因素.结论:IPI可以预测结内DLBCL的预后和生存.采用免疫组化对DLBCL免疫分型对指导治疗有一定意义.R-CHOP免疫化疗能够显著提高结内DLBCL患者的长期生存率. 相似文献
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背景与目的:乙型肝炎病毒(hepatitis virus B,HBV)感染与弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)密切相关,前期研究发现在接受联合免疫化疗的DLBCL患者中,HBsAg阳性者生存较差,但具体机制有待进一步证实。本研究通过分析HBV感染对DLBCL患者细胞免疫的影响,为阐明这一机制寻找细胞免疫方面的证据。方法:2004年3月-2013年6月共294例住院初治的DLBCL患者纳入本研究。采用四色流式分析患者外周血CD3+、CD4+、CD8+细胞计数及CD4+/CD8+细胞比例,比较HBsAg阳性及阴性的DLBCL患者发病时、化疗后2~4个月、化疗后4~6个月及化疗后6~12个月上述参数的时序改变及2组间的差异。结果:与HBsAg阴性患者相比,HBsAg阳性DLBCL患者化疗前各淋巴细胞亚群差异无统计学意义(P>0.05);外周血CD4+细胞计数在化疗后2~4个月显著低于HBsAg阴性患者;HBsAg阳性患者CD4+/CD8+比例降低,在化疗后4~12个月显著低于HBsAg阴性患者。结论:合并HBV感染对DLBCL患者化疗前细胞免疫状态无明显影响;HBsAg阳性的DLBCL患者化疗后出现更为明显和持续的细胞免疫抑制。 相似文献