title: [Cardiac effects of cytokines produced after rituximab infusion].
abstract: Rituximab (Mabthera) is used in the treatment of refractory low-grade non-Hodgkin's lymphoma or in case of relapse after chemotherapy. Among the different adverse reactions with this drug, the most common is a constellation of symptoms (fever, rigors and chills) that occur more frequently during administration of the first dose of drug. These symptoms could be related to a cytokine-release syndrome. We report the case of a 46 year-old patient, presenting a familial cardiomyopathy, deceased a few minutes after having developed this syndrome, at the time of the 2nd infusion of rituximab. Several hypothesis have been suggested to explain this sudden death: a cardiac failure following deterioration of the systolic function, potentially related to the negative inotropic effects of TNFalpha, and/or an impairment of the diastolic function following the volemic overload. The impact of the reflex "administration of monoclonal antibody/cytokine-release syndrome" was only little investigated under physiologic or pathologic conditions. In spite of a risk of adverse reactions apparently moderated compared to the other drugs used in this context, this case report underlines the need for a special attention when using rituximab among patients with cardiac risk factors (reassessment of the benefit-risk ratio, specific monitoring, pre medication). More generally, it underlines the need for a systematic and continuous identification and reporting of adverse drug reactions to the French network of regional pharmacovigilance centres.
authors.affiliation: Service Pharmacie, CHRU Tours, 2, bd Tonnellé, 37044 Tours cedex.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tournamille
authors.forename: Françoise
authors.initials: F
authors.lastname: Rigal-Huguet
authors.forename: Atul
authors.initials: A
authors.lastname: Pathak
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Montastruc
authors.forename: Maryse
authors.initials: M
authors.lastname: Lapeyre-Mestre
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002311:Cardiomyopathy, Dilated / Q000150:complications; D016903:Drug Monitoring; D005047:Etoposide / Q000008:administration & dosage; D017809:Fatal Outcome; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D008935:Mitoguazone / Q000008:administration & dosage; D000069283:Rituximab; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007075:Immunoglobulin M; D000069283:Rituximab; D005047:Etoposide; D008935:Mitoguazone; D007069:Ifosfamide; D008727:Methotrexate