Anti-CD20 therapy for the treatment of chronic Graft Versus Host Disease

2013 ◽  
Author(s):  
Ellen Meijer
Keyword(s):  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Anti Cd20

Risk Reduction of Chronic Graft Versus Host Disease by Anti-CD20 Treatment (Rituximab).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5567-5567
Author(s):  
Marlies E.H.M. Van Hoef
Keyword(s):  
B Cell ◽  
Risk Reduction ◽  
Graft Versus Host Disease ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Host Disease ◽  
Medline Search ◽  
Graft Versus Host ◽  
Anti Cd20 ◽  
Study Plan

Abstract Introduction: Chronic graft versus host disease (cGVHD) occurs in 30–50% of adults transplanted by non-myeloablative (reduced intensity conditioning) allogeneic transplant, whereas it is rare in children. The syndrome complex manifests itselves as auto-immune disease. Dysregulation of B-cell function has also been reported in auto-immune diseases. This is a rationale for B-cell depletion. We considered that B-cell depletion might have a therapeutic effect in cGVHD and reduce the risks associated with cGVHD. Based on these assumptions we applied risk reduction principles and defined a plan for cure of cGVHD. Methods: To identify the risks associated with B-cell depletion in cGVHD we performed a medline search on anti-CD20 or B-cell depletion or rituximab and cGVHD. The publications were analyzed and those applicable to the topic evaluated. Clinical research methods were applied to define a plan for risk reduction of cGVHD. Results: The medline search revealed that rituximab was used for B-cell depletion in cGVHD and in auto-immune diseases. In advanced cGVHD complete and partial remissions of a variety of manifestations of cGVHD were reported. Complete remissions could also be induced early during the disease course of single manifestations of cGVHD not responsive to immune suppressive treatment or as initial treatment. The dose of rituximab varied from 1 to 4 weekly courses of rituximab 375 mg/m2, with repetitions of this schedule in advanced disease to induce complete response. During reported follow-up responding manifestations did not recur. Rituximab treatment was well tolerated with appropriate anti-allergic prophylaxis. The results support the concept that anti-CD20 treatment might cure cGVHD manifestations at first diagnosis; it is too early to define whether it also serves as prophylactic for development of new manifestations. The observations were discussed with the company marketing rituximab and a study plan was designed. This study plan is being discussed with study centers for risk reduction of cGVHD by rituximab. The risk reduction plan will be presented

scholarly journals Treatment of chronic graft-versus-host disease with anti-CD20 chimeric monoclonal antibody

2003 ◽  
Vol 9 (8) ◽  
pp. 505-511 ◽  
Author(s):  
Voravit Ratanatharathorn ◽  
Lois Ayash ◽  
Christopher Reynolds ◽  
Samuel Silver ◽  
Pavan Reddy ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Chimeric Monoclonal Antibody ◽  
Anti Cd20

Paraneoplastic pemphigus

2007 ◽  
Vol 148 (21) ◽  
pp. 979-983 ◽  
Author(s):  
Klaudia Preisz ◽  
Sarolta Kárpáti
Keyword(s):  
Graft Versus Host Disease ◽  
Bronchiolitis Obliterans ◽  
Host Disease ◽  
Graft Versus Host ◽  
Paraneoplastic Pemphigus ◽  
Anti Cd20

A paraneoplasticus pemphigus malignus vagy benignus tumorokhoz társuló autoimmun hólyagos megbetegedés diagnosztikus és immunológiai kritériumait 1990-ben fektette le Anhalt . Klinikailag súlyos, fájdalmas, mélyre terjedő bőr- és nyálkahártyatünetek jellemzik. A bőrtünetek polimorf jellegűek, általában dominál a hólyagképződés. Egyes esetekben, az ún. „graft-versus-host-disease” formákban előfordul, hogy kizárólag papulosus, lichenoid bőrtünetek észlelhetők, hólyagképződés nincs, vagy csak később jelenik meg. Elsősorban ezen alcsoport betegeiben a bőr- és nyálkahártyatünetek mellett súlyos dyspnoét okozó pulmonalis érintettség is kialakul, melynek hátterében bronchiolitis obliterans áll. A paraneoplasticus pemphigus diagnosztikájában alapvető fontosságú a bőr/nyálkahártyák direkt immunfluoreszcens, továbbá a szérum indirekt immunhisztológiai és immunoblot vizsgálata. Az eddig azonosított autoantigének döntő többsége a plakincsalád tagja: envoplakin (210 kDa), periplakin (190 kDa), plectin (~500 kDa), desmoplakin I (250 kDa), desmoplakin II (210 kDa), bullosus pemphigoid antigén 1 (230 kDa). A plakinok mellett a desmosomalis cadherinek közé sorolt desmoglein 1 és 3 a bullosus pemphigoid antigén 2 (180 kDa), a desmocollin 2 és 3, továbbá egy még nem azonosított, 170 kDa molekulatömegű transzmembrán fehérje szintén autoantigénje a kórképnek. A paraneoplasticus pemphigus nagy mortalitású kórkép, az esetek több mint 90%-ában halálos kimenetelű. A háttérben álló tumor eltávolítása mellett a bázisterápia továbbra is a nagy dózisú szisztémás szteroidkezelés, melyet citosztatikumok, immunmodulánsok adásával egészítenek ki. Szóba jön ezenkívül plasmapheresis, plazmacsere, photopheresis, nagy dózisú intravénás immunglobulin és anti-CD20 monoklonális antitest (rituximab) adása is.

Rituximab Reduces the Incidence of Acute Graft Versus Host Disease in an Unselected Series of Twenty-One Patients Undergoing Allogeneic Stem Cell Transplantation at a Single Center.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2875-2875
Author(s):  
M. Christopeit ◽  
L. Mueller ◽  
W. Grothe ◽  
T. Weber ◽  
A. Muetherig ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Graft Versus Host Disease ◽  
Donor Lymphocyte Infusion ◽  
Host Disease ◽  
Graft Versus Host ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20 ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Recent evidence highlights an implication of B lymphocytes in the development and sustainment of chronic graft versus host disease (cGvH). The monoclonal anti-CD20-antibody rituximab has proven effective against steroid refractory cGvH. Data on the role of B lymphocytes in acute GvH (aGvH) is sparse. We report on a reduction of the incidence of aGvH in patients receiving rituximab as an element of conditioning as compared to patients conditioned without rituximab. All 6 patients receiving rituximab suffered from CD20 positive Non-Hodgkin-Lymphoma (NHL) and received cyclosporine and mycophenolate immunosuppression. Immunosuppression in the other 15 patients was achieved either with cyclosporine and mycophenolate (N=11) or cyclosporine and methotrexate (N=4). All patients except for one received dose reduced conditioning. Only patients beyond day 25 are included in the analysis; as of july 20th, 2006 median follow up is 151 days (range 27 to 322 days). Out of six patients receiving rituximab as an element of conditioning, one (16.7 %) developed moderate aGvH. Out of 15 patients who did not receive rituximab during conditioning, 10 (66.7 %) developed moderate to severe aGvH. Two patients developed severe acute GvH after early cessation of immunosuppression and/or donor lymphocyte infusion for progressive disease. If removed from this analysis, 8 out of 13 patients (61.5 %) developed aGvH after conditioning without rituximab. Taken together, these data present a trend that in patients conditioned with rituximab acute GvH occurs less frequently. These are amongst the first data indicating that rituximab might suppress the development of acute GvH. They are in accordance with work published before yet this is the first study systematically comparing two groups of patients. At present, no data exploring the influence of CD20 positive B lymphocytes or the effect of rituximab on graft-versus-tumor effects exist. It therefore remains to be investigated whether the suggested suppression of GvH by rituximab benefits overall survival by reducing transplantation related mortality or whether it is associated with a higher relapse rate due to an abrogated graft versus tumor effect. Furthermore, it remains to be elucidated whether the administration of rituximab before transplantation or during the restoration of the allogeneic immune system exerts prophylactic effects against cGvH and whether this influences both graft versus tumor effects and survival. Finally, we conclude that the addition of rituximab to the treatment of severe steroid refractory acute graft versus host reactions has to be tested in randomized trials.

Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease

Blood ◽  
2004 ◽  
Vol 104 (8) ◽  
pp. 2603-2606 ◽  
Author(s):  
Marijke R. Canninga-van Dijk ◽  
Hanneke M. van der Straaten ◽  
Rob Fijnheer ◽  
Cornelus J. Sanders ◽  
Jan G. van den Tweel ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Autoimmune Diseases ◽  
Graft Versus Host Disease ◽  
Controlled Trial ◽  
Weekly Dose ◽  
Antibody Treatment ◽  
Laboratory Findings ◽  
Host Disease ◽  
Graft Versus Host ◽  
Anti Cd20

Abstract Chronic graft-versus-host disease (cGVHD) is an important determinant of long-term morbidity and mortality in allogeneic stem cell transplantation patients. Because cGVHD has clinical, histologic, and laboratory findings of autoimmune diseases and anti–B-cell therapy has shown efficacy in autoimmune diseases, we hypothesized that monoclonal anti-CD20 antibody therapy might improve patients with cGVHD. We treated 5 men and 1 woman with therapy-refractory extensive cGVHD with anti-CD20 monoclonal antibody. Intravenous infusion was given at a weekly dose of 375 mg/m2 for 4 weeks. In case of incomplete clinical response, additional courses of 4 weeks were given. Five patients responded to treatment with marked clinical, biochemical, and histologic improvement. One patient failed to respond. Anti-CD20 monoclonal antibody seems to be effective in cGVHD. A controlled trial is mandatory to confirm these results. The outcome of this study suggests a participating role of B cells in the pathogenesis of cGVHD.

Sign in / Sign up

Export Citation Format

Share Document