scholarly journals Expression of the oncofetal ED-B–containing fibronectin isoform in hematologic tumors enables ED-B–targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients

Blood ◽  
2009 ◽  
Vol 113 (10) ◽  
pp. 2265-2274 ◽  
Author(s):  
Stefanie Sauer ◽  
Paola A. Erba ◽  
Mario Petrini ◽  
Andreas Menrad ◽  
Leonardo Giovannoni ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Hodgkin Lymphoma ◽  
Hematologic Malignancies ◽  
Current Treatment ◽  
Cancer Therapies ◽  
Bone Marrow Biopsies ◽  
Normal Tissues ◽  
Non Hodgkin Lymphoma ◽  
Promising Target

Abstract Current treatment of hematologic malignancies involves rather unspecific chemotherapy, frequently resulting in severe adverse events. Thus, modern clinical research focuses on compounds able to discriminate malignant from normal tissues. Being expressed in newly formed blood vessels of solid cancers but not in normal mature tissues, the extradomain B of fibronectin (ED-B FN) is a promising target for selective cancer therapies. Using immunohistology with a new epitope retrieval technique for paraffin-embedded tissues, ED-B FN expression was found in biopsies from more than 200 Hodgkin and non-Hodgkin lymphoma patients of nearly all entities, and in patients with myeloproliferative diseases. ED-B FN expression was nearly absent in normal lymph nodes (n = 10) and bone marrow biopsies (n = 9). The extent of vascular ED-B FN expression in lymphoma tissues was positively correlated with grade of malignancy. ED-B FN expression was enhanced in lymph nodes with severe lymphadenopathy and in some hyperplastic tonsils. The in vivo accessibility of ED-B FN was confirmed in 3 lymphoma patients, in whom the lymphoma lesions were visualized on scintigraphy with 131I-labeled L19 small immunoprotein (131I-L19SIP). In 2 relapsed Hodgkin lymphoma patients131I-L19SIP radioimmunotherapy induced a sustained partial response, qualifying ED-B FN as a promising target for antibody-based lymphoma therapies.

Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro and in vivo antitumor activities

Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 1185-1192 ◽  
Author(s):  
Julie A. McEarchern ◽  
Ezogelin Oflazoglu ◽  
Leigh Francisco ◽  
Charlotte F. McDonagh ◽  
Kristine A. Gordon ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hematologic Malignancies ◽  
Effector Cells ◽  
Effector Functions ◽  
Normal Tissues ◽  
Non Hodgkin Lymphoma ◽  
Human Igg1 ◽  
Constant Domains

Abstract Antigens expressed on malignant cells in the absence of significant expression on normal tissues are highly desirable targets for therapeutic antibodies. CD70 is a TNF superfamily member whose normal expression is highly restricted but is aberrantly expressed in hematologic malignancies including non-Hodgkin lymphoma (NHL), Hodgkin disease, and multiple myeloma. In addition, solid tumors such as renal cell carcinoma, nasopharyngeal carcinoma, thymic carcinoma, meduloblastoma, and glioblastoma express high levels of this antigen. To functionally target CD70-expressing cancers, a murine anti-CD70 monoclonal antibody was engineered to contain human IgG1 constant domains. The engineered antibody retained the binding specificity of the murine parent monoclonal antibody and was shown to induce Fc-mediated effector functions including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis in vitro. Further, administration of this antibody significantly prolonged survival of severe combined immunodeficient (SCID) mice bearing CD70+ disseminated human NHL xenografts. Survival of these mice was dependent upon the activity of resident effector cells including neutrophils, macrophages, and natural killer (NK) cells. These data suggest that an anti-CD70 antibody, when engineered to contain human IgG1 constant domains, possesses effector cell–mediated antitumor activity and has potential utility for anticancer therapy.

Thrombotic complications in adult patients with lymphoma: a meta-analysis of 29 independent cohorts including 18 018 patients and 1149 events

Blood ◽  
2010 ◽  
Vol 115 (26) ◽  
pp. 5322-5328 ◽  
Author(s):  
Vanesa Caruso ◽  
Augusto Di Castelnuovo ◽  
Susana Meschengieser ◽  
Maria A. Lazzari ◽  
Giovanni de Gaetano ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Meta Analysis ◽  
Hematologic Malignancies ◽  
Incidence Rates ◽  
Clinical Implications ◽  
Low Grade ◽  
Thrombotic Risk ◽  
Non Hodgkin Lymphoma ◽  
Thrombotic Complications ◽  
Exact Maximum Likelihood

AbstractThrombotic complications in hematologic malignancies have important clinical implications. In this meta-analysis we sought to obtain accurate estimates of the thrombotic risk in lymphoma patients. Articles were searched in electronic databases and references. Eighteen articles were identified (29 cohorts, 18 018 patients and 1149 events). Pooled incidence rates (IRs) were calculated by the use of a method based on the exact maximum likelihood binomial distribution. The global IR of thrombosis was 6.4% (95% confidence interval [CI] 6.0%-6.8%). The global IRs of venous or arterial events were 5.3% (95% CI, 5.0%-5.7%) and 1.1% (95% CI, 0.9%-1.2%), respectively. The IR of thrombosis observed in subjects with non-Hodgkin lymphoma (NHL) was 6.5% (95% CI, 6.1%-6.9%), significantly greater than that observed for patients with Hodgkin lymphoma (4.7%; 95% CI, 3.9%-5.6%). Within NHL, patients with high-grade disease had a greater risk of events (IR 8.3%; 95% CI, 7.0%-9.9%) than low-grade disease (IR 6.3%; 95% CI, 4.5%-8.9%). This meta-analysis shows that the IR of thrombosis in lymphoma patients is quite high, especially in those with NHL at an advanced stage of the disease. These results may help better defining lymphoma populations at high thrombotic risk, to whom prophylactic approaches could be preferentially applied.

scholarly journals SMARCAL1 deficiency predisposes to non-Hodgkin lymphoma and hypersensitivity to genotoxic agents in vivo

2012 ◽  
Vol 158A (9) ◽  
pp. 2204-2213 ◽  
Author(s):  
Alireza Baradaran-Heravi ◽  
Anja Raams ◽  
Joanna Lubieniecka ◽  
Kyoung Sang Cho ◽  
Kristi A. DeHaai ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Genotoxic Agents

scholarly journals Daratumumab displays in vitro and in vivo anti-tumor activity in models of B-cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens

Haematologica ◽  
2019 ◽  
Vol 105 (4) ◽  
pp. 1032-1041 ◽  
Author(s):  
Anna Vidal-Crespo ◽  
Alba Matas-Céspedes ◽  
Vanina Rodriguez ◽  
Cédric Rossi ◽  
Juan G. Valero ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Anti Tumor Activity

The Comparison of Efficacy Between MVEP Chemotherapy and R- MVEP Chemotherapy in Patients of Refractory and Relapsed Non-Hodgkin Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4963-4963
Author(s):  
Meihua Qian ◽  
Wensong Wang
Keyword(s):  
Complete Remission ◽  
Lymph Nodes ◽  
Hodgkin Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Treatment Method ◽  
Old Patients ◽  
Overall Response ◽  
Non Hodgkin Lymphoma ◽  
Better Than

Abstract To observe the efficacy and toxicity of two groups of MVEP Chemotherapy and R-MVEP Chemotherapy in patients of Refractory and relapsed Non-Hodgkin Lymphoma. 19 cases patients of refractory and relapsed Non-Hodgkin Lymphoma, 9 females and 10 male, between 17–75 years of age (mean age 45.5 years), 2 cases IIa,, 11caseIII (9IIIa and 2IIIb), 6 cases IV(4 IVa and 2 IVb).Most of patients showed the enlargement of superficial and/or deep multiple lymph nodes, 4 cases had fever and the enlargement of spleen and/or liver, 2 cases with hydrothorax and ascites, 3 cases with bone marrow infiltration and 1 case with multiple lumps in liver, other 1 case with autoimmune hemolytic anemia (AIHA)and one with pericardial effusion. All patients were treated with chemotherapy included COP (or COPP), CHOP, BCAOP (or BECAOP), etc. and 2 patients of them Had been treated by radiotherapy before they were treated by MVEP Chemotherapy and R- MVEP Chemotherapy. In this experiment, A group of 13 patients were treated by MVEP Chemotherapy and G-CSF ( MVEP, Mitoxantrone 8mg/m2/d1, VP16 O.1/d1 ‘d5 (or,Wumon 0.1/d1 ‘d3),Vinorelbinum 20mg/m2/d1,Prednison 60mg/d1 ‘d7,or DXM 8mg/m2d1 ‘d7), other group of 6 patients were therapied by Rituximab plus MEVP Chemotherapy and G-CSF,( R-MVEP, Rituximab 375 mg/m2/d1,Mitoxantrone 8mg/m2/d3, Wumon 0.1/d3 ‘d5 (or VP16 O.1/d3 ‘d7),Vinorelbinum 20mg/m2/d3,Prednison 60mg/d3 ‘d9 (or DXM 8mg/m2d3 ‘d9 ), G-CSF 100 ‘300/d were injected when the number of WBC was <2.0×109/L after chemotherapy. Each cycle was 28–35 days and assessment was given after 2 cycles. The result is, The overall response rate and complete remission was 61.5 % and 38.4% respectively in treat group of MVEP, The overall response rate and complete remission was 83.3% and 50 % respectively in group of R- MVEP. One of patients of NHL with AIHA after a treating cycle achieved complete remission(all of enlarged lymph nodes disappeared and Hemoglobin return to normal).The main toxicity was mylosuppression, the minimum of WBC after chemotherapy reached 0.5 ‘1.4*109/L, few patients vomited during chemotherapy, All toxicity was no different in two groups of MVEP and R-MVEP BOur study result indicates: MEVP Chemotherapy and G-CSF is an Effective, safety and economy on patients of Refractory and relapsed Non-Hodgkin Lymphoma, but Rituximab in Combination with MEVP Chemotherapy and G-CSF is could improve the efficacy of MEVP Chemotherapy only in patients of Refractory and relapsed Non-Hodgkin Lymphoma. The efficacy of Rituximab in Combination with MEVP Chemotherapy is much better than that of MVEP Chemotherapy only on patients of Refractory and relapsed Non-Hodgkin Lymphoma, the treatment method of R-MVEP are suitable for old patients.

Underreporting of Myelotoxicity with Emerging Regimens for Selected Hematologic Malignancies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1501-1501
Author(s):  
Stephanie A. Gregory ◽  
Steve Abella ◽  
Timothy Moore
Keyword(s):  
Hodgkin Lymphoma ◽  
Research Funding ◽  
English Language ◽  
Antibiotic Use ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Phase 3 ◽  
Non Hodgkin Lymphoma ◽  
Prophylactic Use ◽  
Clinically Significant

Abstract Abstract 1501 Background: Clinical data guiding colony-stimulating factor (CSF) use with emerging regimens that incorporate targeted agents for treating hematologic malignancies are not readily available, even though many of these regimens can produce increased myelosuppressive side-effects. This review assessed the diligence of reporting around neutropenia, febrile neutropenia (FN), and neutropenic complications as well as the use of CSF and antibiotics in published clinical trials evaluating emerging regimens for the treatment of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, multiple myeloma (MM), or chronic lymphocytic leukemia (CLL). Methods: English-language reports of randomized controlled phase 3 studies of the selected hematologic malignancies published between January 2005 and June 2009 were identified by searching Medline, EMBASE, and Cochrane databases. Publications that met the inclusion criteria were retrieved and data on the incidence of neutropenia and its complications and CSF/antibiotic use were extracted. The percentage of publications that reported each outcome was then calculated. Results: Fifty seven trials that met the criteria were included in this analysis. Overall, 68% of trials reported on the incidence of grade 3/4 neutropenia (80%, MM; 71% CLL; 63% NHL, and 50%, Hodgkin lymphoma). However, fewer trials (18%) reported on the incidence of FN (57%, CLL; 20%, MM; 8%, NHL; and 0%, Hodgkin lymphoma). Similarly, only a few trials (4%) reported neutropenia-related hospitalizations (8%, NHL; 0% each for Hodgkin lymphoma, MM, and CLL). Primary prophylactic use of CSF was defined in the methods section of 19% of trials and CSF use was reported in the results section of 25% of trials. Use of antibiotics for FN treatment was defined in the methods section of 2% of trials and was reported in the results section of 9% of trials. Conclusion: In the published phase 3 studies evaluated in this analysis, clinically significant neutropenia and neutropenia-related events (including FN) were poorly or generally not described. Furthermore, the use of CSF and antibiotics was infrequently and inconsistently reported in the published literature of emerging regimens. A standardized approach to reporting neutropenic outcomes and the related use of supportive care measures can assist clinicians to prospectively manage the relevant toxicities associated with emerging regimens for hematologic malignancies. This is essential for the safe and effective transition of these regimens into broad clinical practice. Disclosures: Gregory: Amgen Inc.: Consultancy; Astellas: Research Funding; Celgene: Research Funding; Cephalon: Research Funding, Speakers Bureau; Genentech (Roche): Consultancy, Research Funding, Speakers Bureau; GlaxoSmithKline: Research Funding; Immunomedics: Research Funding; NCIC CTG: Research Funding; Novartis: Consultancy, Research Funding; Onyx: Research Funding; Spectrum Pharmaceuticals: Consultancy. Abella:Amgen Inc.: Employment, Equity Ownership. Moore:Amgen Inc.: Consultancy, Honoraria.

Aberrant Expression of Golgin-84 in Non-Hodgkin Lymphomas and Plasma Cell Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4633-4633
Author(s):  
Ling Chen ◽  
Yaling Yang ◽  
C. Cameron Yin ◽  
Gary Lu ◽  
Su Chen ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Plasma Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoid Cells ◽  
Plasma Cell Myeloma ◽  
Expression Levels ◽  
Non Hodgkin Lymphoma

Abstract Abstract 4633 Background: Golgins are proteins of the Golgi complex. Several Golgins have been implicated in apoptosis. Expression of Golgin-84, a Golgin protein, is altered in apoptotic WEHI-231, a B-cell lymphoma line, suggesting that Golgin-84 may play a role in lymphoid tumorigenesis. Here, we aimed to determine the expression levels of Golgin-84 in human primary non-Hodgkin lymphomas and plasma cell myeloma. Design: Golgin-84 expression was investigated in non-Hodgkin lymphoma cell lines by using Western blot analysis and polyclonal antibodies. Using immunohistochemical stains, Western blotting analysis and Q-PCR, Golgin-84 expression was assessed in 5 reactive lymph nodes, 149 cases of primary non-Hodgkin lymphoma and 28 cases of primary plasma cell myeloma. Results: Immunohistochemical stains, Western blotting analysis and Q-PCR on 5 reactive lymph nodes demonstrated that Golgin-84 was expressed at low levels in lymphoid cells of germinal centers, mantle cells, marginal zones, and interfollicular areas. Golgin-84 was variably expressed in non-Hodgkin lymphoma cell lines tested, with the highest levels in cells from high-grade tumors (e.g. anaplastic large cell lymphoma; ALCL, Diffuse large B-cell lymphoma (DLBCL), ALCL and peripheral T-cell lymphoma unspecified (PTCL)) and the lowest levels in mantle cell lymphoma (MCL) cells. DLBCL, ALCL and PTCL frequently showed high expression of Golgin-84. Most lymphoplasmacytic lymphomas (LPL) and plasma cell myeloma (PCM) expressed high levels of Golgin-84. Expression levels of Golgin-84 were lower in MCL and low-grade B-cell non-Hodgkin lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). Conclusions: Golgin-84 expression levels are low in lymphoid cells of normal lymph nodes. Most (>90%) cases of LPL and PCM, and at least half of cases of DLBCL, ALCL and PTCL express high levels of Golgin-84. These findings suggest that Golgin-84 may be involved in tumorigenesis or lymphoma progression, particularly in neoplasms with plasmacytic differentiation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals In Vitro and In Vivo Interactions between the HDAC6 Inhibitor Ricolinostat (ACY1215) and the Irreversible Proteasome Inhibitor Carfilzomib in Non-Hodgkin Lymphoma Cells

2014 ◽  
Vol 13 (12) ◽  
pp. 2886-2897 ◽  
Author(s):  
Girija Dasmahapatra ◽  
Hiral Patel ◽  
Johnathan Friedberg ◽  
Steven N. Quayle ◽  
Simon S. Jones ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Proteasome Inhibitor ◽  
Lymphoma Cells ◽  
Non Hodgkin Lymphoma ◽  
Hdac6 Inhibitor

scholarly journals Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma

Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1311-1314 ◽  
Author(s):  
Ioanna Papandreou ◽  
Nicholas C. Denko ◽  
Michael Olson ◽  
Heleen Van Melckebeke ◽  
Sofie Lust ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Kinase Activity ◽  
Specific Inhibitor ◽  
Hematologic Malignancies ◽  
Promising Target ◽  
Molecule Inhibitor ◽  
Human Multiple Myeloma ◽  
Isolated Cell

Abstract Activation of the adaptive Ire1-XBP1 pathway has been identified in many solid tumors and hematologic malignancies, including multiple myeloma (MM). Here, we report the identification of STF-083010, a novel small-molecule inhibitor of Ire1. STF-083010 inhibited Ire1 endonuclease activity, without affecting its kinase activity, after endoplasmic reticulum stress both in vitro and in vivo. Treatment with STF-083010 showed significant antimyeloma activity in model human MM xenografts. Similarly, STF-083010 was preferentially toxic to freshly isolated human CD138+ MM cells compared with other similarly isolated cell populations. The identification of this novel Ire1 inhibitor supports the hypothesis that the Ire1-XBP1 axis is a promising target for anticancer therapy, especially in the context of MM.

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