Pathogenic study of anti-CD20 infusion-related severe refractory shock in diffuse large B-cell lymphoma.
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.
Gutiérrez
Antonio
A
Department of Hematology, University Hospital Son Dureta, Palma de Mallorca, Balearic Islands, Spain. agutierrez@hsd.es
Rodríguez
José
J
Martínez
Jordi
J
Amezaga
Rocío
R
Ramos
Rafael
R
Galmes
Bernat
B
Bea
Maria Dolores
MD
Ferrer
Joana
J
Pons
Jaume
J
Sampol
Antonia
A
Morey
Miguel
M
Duran
María Antonia
MA
Raurich
Joan
J
Besalduch
Joan
J
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
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D016207:Cytokines; D000069283:Rituximab