title: Pathogenic study of anti-CD20 infusion-related severe refractory shock in diffuse large B-cell lymphoma.
abstract: Although rituximab is an effective and safe therapy for B-cell lymphoid malignancies, a few cases of severe infusion-related reactions have been reported. Severe refractory distributive shock is an infrequent side-effect of treatment with rituximab and, to our knowledge, there are no reports describing its pathogenesis in a case of fatal outcome in detail. We present for the first time a case of fatal rituximab infusion-related refractory distributive shock in a patient with CD5+ diffuse large B-cell lymphoma (DLBCL) and analyse the pathogenic mechanisms involved. We have compared measurements obtained from the patient that experienced lethal refractory shock with the four subsequent DLBCL patients treated with rituximab, either at diagnosis or upon relapse, at our center. Serum cytokines [interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70] and complement components C3 and C4 were analysed, both pretreatment, and 3 h and 9 h after the onset of infusion. When compared with the control subjects, the potential risk factors for rituximab toxicity displayed by the patient that suffered refractory shock included C4 hypercomplementemia, IFN-gamma and IL-10 hypercytokinemia, as well as a high tumor burden. The refractory shock was distributive with most cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6 and IL-8) peaking 3 h after infusion and coinciding with the onset of the shock. Furthermore, the concentrations of IL-10 were persistently elevated. In conclusion, the cytokine pattern was similar to that observed in patients with rapid onset septic shock and serum cytokines reached levels markedly higher than previously described in other cases of severe rituximab infusion-related toxicity.
authors.affiliation: Department of Hematology, University Hospital Son Dureta, Palma de Mallorca, Balearic Islands, Spain. agutierrez@hsd.es
authors.forename: Antonio
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: José
authors.initials: J
authors.lastname: Rodríguez
authors.forename: Jordi
authors.initials: J
authors.lastname: Martínez
authors.forename: Rocío
authors.initials: R
authors.lastname: Amezaga
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramos
authors.forename: Bernat
authors.initials: B
authors.lastname: Galmes
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Bea
authors.forename: Joana
authors.initials: J
authors.lastname: Ferrer
authors.forename: Jaume
authors.initials: J
authors.lastname: Pons
authors.forename: Antonia
authors.initials: A
authors.lastname: Sampol
authors.forename: Miguel
authors.initials: M
authors.lastname: Morey
authors.forename: María Antonia
authors.initials: MA
authors.lastname: Duran
authors.forename: Joan
authors.initials: J
authors.lastname: Raurich
authors.forename: Joan
authors.initials: J
authors.lastname: Besalduch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D000069283:Rituximab; D012769:Shock / Q000276:immunology / Q000503:physiopathology*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D016207:Cytokines; D000069283:Rituximab