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Titolo:
Complement activation in circulation and central nervous system after Rituximab (Anti-CD20) treatment of B-Cell lymphoma
Autore:
Harjunpaa, A; Wiklund, T; Collan, J; Janes, R; Rosenberg, J; Lee, D; Grillo-Lopez, A; Meri, S;
Indirizzi:
Univ Helsinki, Dept Bacteriol & Immunol, Haartman Inst, FIN-00014 Helsinki, Finland Univ Helsinki Helsinki Finland FIN-00014 st, FIN-00014 Helsinki, Finland
Titolo Testata:
LEUKEMIA & LYMPHOMA
fascicolo: 4, volume: 42, anno: 2001,
pagine: 731 - 738
SICI:
1042-8194(200108)42:4<731:CAICAC>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
MONOCLONAL-ANTIBODY THERAPY; NON-HODGKINS-LYMPHOMA; TUMOR-CELLS; LOW-GRADE; ASSOCIATION; INHIBITION; BLOOD;
Keywords:
Rituxan; Mabthera; intrathecal treatment; blood-brain barrier; immunotherapy; anti CD20-antibodies;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
16
Recensione:
Indirizzi per estratti:
Indirizzo: Meri, S Univ Helsinki, Dept Bacteriol & Immunol, Haartman Inst, POB 21,Haartmaninkatu 3, FIN-00014 Helsinki, Finland Univ Helsinki POB 21,Haartmaninkatu 3 Helsinki Finland FIN-00014
Citazione:
A. Harjunpaa et al., "Complement activation in circulation and central nervous system after Rituximab (Anti-CD20) treatment of B-Cell lymphoma", LEUK LYMPH, 42(4), 2001, pp. 731-738

Abstract

Rituximab (IDEC-C2B8, Mabthera (R), Rituxan (R)), a chimeric monoclonal antibody against the B-cell specific CD20-antigen, has been demonstrated to be effective in the treatment of non-Hodgkin's B-cell lymphoma (B-NHL). Previous in vitro studies have shown that direct complement-dependent cytotoxicity (CDC), ADCC and apoptosis are important in the rituximab-induced killing of lymphoma cells. It is, however, unknown whether rituximab penetrates the blood-brain barrier. Therefore, we studied rituximab levels and complement (C) activation in blood and cerebrospinal fluid (CSF) following intravenous rituximab therapy in a patient with relapsing non-Hodgkin's lymphoma with central nervous system (CNS) involvement. Longitudinal samples from blood and CSF were taken at 13 time-points during the treatment period. The results show that the C cascade becomes activated in blood during the First mAb infusion (C3a-desArg concentration rose from 55 to 138 mug/ml during the first 2 hours). After the first infusion the proportions of lymphocytes positive for the CD19- and CD20-antigens in the peripheral blood were reduced from 41 % and 35 %, respectively, to a level of 2 % (for both). In CSF the rituximab concentration increased after successive infusions, but remained below 0.55 mug/ml (compared to a C-max of 400 mug/ml in peripheral blood), Although a minor and delayed C activation response was seen in the CSF the treatment did not clear CD20-positive cells away from the CNS. Thus, it appears that an intact blood-brain barrier restricts the entry of rituximab into the CNS. Possible options to circumvent this would be dose escalation orintrathecal rituximab treatment.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 07:11:21