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Eric Oksenhendler - One of the best experts on this subject based on the ideXlab platform.
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hiv associated multicentric Castleman disease
Current Opinion in Hiv and Aids, 2009Co-Authors: Eric OksenhendlerAbstract:Multicentric Castleman’s disease (MCD) is a rare but potentially fatal lymphoproliferative disorder that shows a close association with human herpesvirus-8 (HHV-8) infection. Interleukin-6 dysregulation is thought to be fundamental to its pathogenesis. MCD is characterized by recurrent flares with fever, lymphadenopathy, splenomegaly, and heterogeneous systemic manifestations, associated with cytopenia, raised inflammatory markers, and high HHV-8 viral load in the blood. During the recent years, the widespread use of combination antiretroviral therapy and the introduction of rituximab have dramatically improved the treatment of HIV-MCD.
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Extracavitary tumor after primary effusion lymphoma: relapse or second distinct lymphoma?
Haematologica, 2007Co-Authors: Emmanuelle Boulanger, Veronique Meignin, Philippe V Afonso, Renan Duprez, Eric Oksenhendler, Félix Agbalika, Antoine GessainAbstract:HHV-8-associated solid lymphomas which develop in extracavitary sites during the course of primary effusion lymphoma (PEL) could represent the relapse of original PEL tumors in different anatomical sites, or newly occurring distinct HHV-8-associated lymphomas, such as multicentric Castleman disease-related microlymphomas. HHV-8 episome clonality might help identify which event takes place.
Emmanuelle Boulanger - One of the best experts on this subject based on the ideXlab platform.
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Extracavitary tumor after primary effusion lymphoma: relapse or second distinct lymphoma?
Haematologica, 2007Co-Authors: Emmanuelle Boulanger, Veronique Meignin, Philippe V Afonso, Renan Duprez, Eric Oksenhendler, Félix Agbalika, Antoine GessainAbstract:HHV-8-associated solid lymphomas which develop in extracavitary sites during the course of primary effusion lymphoma (PEL) could represent the relapse of original PEL tumors in different anatomical sites, or newly occurring distinct HHV-8-associated lymphomas, such as multicentric Castleman disease-related microlymphomas. HHV-8 episome clonality might help identify which event takes place.
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prospective study of rituximab in chemotherapy dependent human immunodeficiency virus associated multicentric Castleman s disease anrs 117 castlemab trial
Journal of Clinical Oncology, 2007Co-Authors: Laurence Gerard, Alice Berezne, Lionel Galicier, Veronique Meignin, Martine Obadia, Nathalie De Castro, Christine Jacomet, R Verdon, Isabelle Madelainechambrin, Emmanuelle BoulangerAbstract:Purpose Single-agent chemotherapy is usually effective in HIV-associated multicentric Castleman's disease (MCD). However, in most patients, chemotherapy cannot be discontinued. Patients and Methods To evaluate the efficacy of four weekly rituximab infusions (375 mg/m2) after discontinuation of chemotherapy in HIV-associated MCD, 24 patients were enrolled onto a prospective open-label trial. Results At study entry, the median time from MCD diagnosis was 21 months. All patients had stable disease on chemotherapy and were dependent on chemotherapy for a median time of 13 months. The median CD4 cell count was 270 × 106/L, and the plasma HIV RNA was less than 50 copies/mL in 18 patients. One patient died with progressive disease at day 15, and 23 patients completed the four cycles of rituximab. Sustained remission (SR) off treatment at day 60 (primary end point) was achieved in 22 patients (92%). From day 60 to day 365, one patient died with acute respiratory failure of undetermined origin, and four patients e...
Corey Casper - One of the best experts on this subject based on the ideXlab platform.
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Castleman disease spectrum
Journal of Clinical Oncology, 2020Co-Authors: Johnson Khor, Sheila K Pierson, Victoria Powers, Markavery Tamakloe, Alexander Gorzewski, Katherine Floess, Jasira Ziglar, Eric Haljasmaa, Yue Ren, Corey CasperAbstract:8548Background: Castleman disease (CD) describes a group of lymphoproliferative disorders that share characteristic histopathology. Unicentric CD (UCD) and idiopathic multicentric CD (iMCD) are dif...
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a phase i open label study of siltuximab an anti il 6 monoclonal antibody in patients with b cell non hodgkin lymphoma multiple myeloma or Castleman disease
Clinical Cancer Research, 2013Co-Authors: Razelle Kurzrock, Peter M Voorhees, Corey Casper, Richard R Furman, Luis Fayad, Sagar Lonial, Hossein Borghaei, Sundar Jagannath, Lubomir Sokol, Saad Z UsmaniAbstract:Purpose: To evaluate the safety and pharmacokinetics of siltuximab, an anti–interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease. Experimental Design: In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks. Response was assessed in all disease types. Clinical benefit response (CBR; composite of hemoglobin, fatigue, anorexia, fever/night sweats, weight, largest lymph node size) was also evaluated in Castleman disease. Results: Sixty-seven patients received a median of 16 siltuximab doses for a median of 8.5 (maximum 60.5) months; 29 were treated 1 year or longer. There was no dose-limiting toxicity, antibodies to siltuximab, or apparent dose–toxicity relationship. The most frequently reported possible drug-related adverse events were thrombocytopenia (25%), hypertriglyceridemia (19%), neutropenia (19%), leukopenia (18%), hypercholesterolemia (15%), and anemia (10%). None of these events led to dose delay/discontinuation except for neutropenia and thrombocytopenia ( n = 1 each). No treatment-related deaths occurred. C-reactive protein (CRP) suppression was most pronounced at 12 mg/kg every 3 weeks. Mean terminal-phase half-life of siltuximab ranged 17.73 to 20.64 days. Thirty-two of 37 (86%) patients with Castleman disease improved in 1 or more CBR component; 12 of 36 evaluable Castleman disease patients had radiologic response [complete response (CR), n = 1; partial response (PR), n = 11], including 8 of 19 treated with 12 mg/kg; 2 of 14 (14%) evaluable NHL patients had PR; 2 of 13 (15%) patients with multiple myeloma had CR. Conclusion: No dose-related or cumulative toxicity was apparent across all disease indications. A dose of 12 mg/kg every 3 weeks was recommended on the basis of the high response rates in Castleman disease and the sustained CRP suppression. Randomized studies are ongoing in Castleman disease and multiple myeloma. Clin Cancer Res; 19(13); 3659–70. ©2013 AACR .
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a phase i open label study of siltuximab an anti il 6 monoclonal antibody in patients with b cell non hodgkin lymphoma multiple myeloma or Castleman disease
Clinical Cancer Research, 2013Co-Authors: Razelle Kurzrock, Peter M Voorhees, Corey Casper, Richard R Furman, Luis Fayad, Sagar Lonial, Hossein Borghaei, Sundar Jagannath, Lubomir Sokol, Saad Z UsmaniAbstract:Purpose: To evaluate the safety and pharmacokinetics of siltuximab, an anti–interleukin-6 chimeric monoclonal antibody (mAb) in patients with B-cell non-Hodgkin lymphoma (NHL), multiple myeloma, or Castleman disease. Experimental Design: In an open-label, dose-finding, 7 cohort, phase I study, patients with NHL, multiple myeloma, or symptomatic Castleman disease received siltuximab 3, 6, 9, or 12 mg/kg weekly, every 2 weeks, or every 3 weeks. Response was assessed in all disease types. Clinical benefit response (CBR; composite of hemoglobin, fatigue, anorexia, fever/night sweats, weight, largest lymph node size) was also evaluated in Castleman disease. Results: Sixty-seven patients received a median of 16 siltuximab doses for a median of 8.5 (maximum 60.5) months; 29 were treated 1 year or longer. There was no dose-limiting toxicity, antibodies to siltuximab, or apparent dose–toxicity relationship. The most frequently reported possible drug-related adverse events were thrombocytopenia (25%), hypertriglyceridemia (19%), neutropenia (19%), leukopenia (18%), hypercholesterolemia (15%), and anemia (10%). None of these events led to dose delay/discontinuation except for neutropenia and thrombocytopenia ( n = 1 each). No treatment-related deaths occurred. C-reactive protein (CRP) suppression was most pronounced at 12 mg/kg every 3 weeks. Mean terminal-phase half-life of siltuximab ranged 17.73 to 20.64 days. Thirty-two of 37 (86%) patients with Castleman disease improved in 1 or more CBR component; 12 of 36 evaluable Castleman disease patients had radiologic response [complete response (CR), n = 1; partial response (PR), n = 11], including 8 of 19 treated with 12 mg/kg; 2 of 14 (14%) evaluable NHL patients had PR; 2 of 13 (15%) patients with multiple myeloma had CR. Conclusion: No dose-related or cumulative toxicity was apparent across all disease indications. A dose of 12 mg/kg every 3 weeks was recommended on the basis of the high response rates in Castleman disease and the sustained CRP suppression. Randomized studies are ongoing in Castleman disease and multiple myeloma. Clin Cancer Res; 19(13); 3659–70. ©2013 AACR .
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the aetiology and management of Castleman disease at 50 years translating pathophysiology to patient care
British Journal of Haematology, 2005Co-Authors: Corey CasperAbstract:Summary Fifty years ago, Dr Benjamin Castleman first described the unusual lymphoproliferative disorder that now bears his name. Over the subsequent decades, astute clinical and pathologic observations coupled with clever molecular biologic research have increased our understanding of the aetiology of Castleman disease (CD). This article proposes three broad CD variants based on both distinctive histopathology and clinical behaviour. The pivotal roles of infection with human herpesvirus 8 and interleukin-6 production in the development of CD are emphasized. Finally, the natural history of CD and the myriad of therapeutic options are reviewed in the context of a unified model of CD pathophysiology, and continued areas of uncertainty are discussed.
Hiroaki Mitsuya - One of the best experts on this subject based on the ideXlab platform.
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Successful treatment of TAFRO syndrome, a variant type of multicentric Castleman disease with thrombotic microangiopathy, with anti-IL-6 receptor antibody and steroids
International Journal of Hematology, 2016Co-Authors: Shiho Fujiwara, Hiromi Mochinaga, Hirotomo Nakata, Koichi Ohshima, Masanori Matsumoto, Mitsuhiro Uchiba, Yoshiki Mikami, Hiroyuki Hata, Yutaka Okuno, Hiroaki MitsuyaAbstract:TAFRO syndrome is a rare variant type of multicentric Castleman disease, which is characterized by thrombocytopenia, anasarca, reticulin fibrosis of bone marrow, renal dysfunction and organomegaly. Here, we report a case of TAFRO syndrome that was successfully treated with tocilizumab. A 50-year-old man, who presented with fever, epigastric pain, abdominal fullness, and massive edema of the extremities, was admitted to our hospital. Computed tomography revealed bilateral pleural effusions, ascites, and lymphadenopathy. Laboratory data showed renal dysfunction, anemia, and thrombocytopenia. Examination of bone marrow and cervical lymph nodes led to a diagnosis of hyaline vascular-type Castleman disease. The level of serum interleukin (IL)-6 was extremely high. TAFRO syndrome was finally diagnosed. The patient was treated weekly with tocilizumab, an anti-IL-6 receptor antibody and steroids. In 4 weeks, all symptoms disappeared and serum IL-6 level returned to normal. Activity of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), which was significantly decreased (9.9 %) prior to treatment, increased after treatment with tocilizumab. The present case suggests that tocilizumab is an effective therapeutic agent for TAFRO syndrome. We suggest that hypercytokinemia in TAFRO syndrome inhibits ADAMTS13 activity, thereby inducing thrombotic microangiopathy.
Antoine Gessain - One of the best experts on this subject based on the ideXlab platform.
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Extracavitary tumor after primary effusion lymphoma: relapse or second distinct lymphoma?
Haematologica, 2007Co-Authors: Emmanuelle Boulanger, Veronique Meignin, Philippe V Afonso, Renan Duprez, Eric Oksenhendler, Félix Agbalika, Antoine GessainAbstract:HHV-8-associated solid lymphomas which develop in extracavitary sites during the course of primary effusion lymphoma (PEL) could represent the relapse of original PEL tumors in different anatomical sites, or newly occurring distinct HHV-8-associated lymphomas, such as multicentric Castleman disease-related microlymphomas. HHV-8 episome clonality might help identify which event takes place.