title: Risk of infection in patients with lymphoma receiving rituximab: systematic review and meta-analysis.
abstract: BACKGROUND
  The addition of Rituximab (R) to standard chemotherapy (C) has been reported to improve the end of treatment outcome in patients affected by CD-20 positive malignant lymphomas (CD20+ ML). Nevertheless, given the profound and prolonged immunosuppression produced by R there are concerns that severe infections may arise. A systematic review and meta-analysis were performed to determine whether or not the addition of R to C may increase the risk of severe infections in adults undergoing induction therapy for CD20+ ML.
  
  
  METHODS
  Only randomised controlled trials comparing R-C to C standard alone in adult patients with CD20+ ML were included. Meta-analysis was performed on overall incidence of severe infection, risk of dying as the consequence of infection, risk of febrile neutropenia, risk of severe leucopenia, risk of severe granulocytopenia and overall response assuming a fixed effect model. Heterogeneity was investigated, if present and I2 >20%, according to several predefined baseline characteristics of the study populations.
  
  
  RESULTS
  Several relevant results have emerged. First, the addition of R to standard C does not increase the overall risk of severe infections (RR = 1.00; 95% CI 0.87 to 1.14) nor does it increase the risk of dying as a consequence of infection (RR = 1.60; 95% CI 0.68 to 3.75). Second, we confirmed that the addition of R to standard C increases the proportion of overall response (RR = 1.12; 95% CI 1.09 to 1.15), but it also increases the risk of severe leucopenia (RR = 1.24; 95% CI 1.12 to 1.37) and granulocytopenia (RR = 1.07; 95% CI 1.02 to 1.12).
  
  
  CONCLUSIONS
  R-C is superior to standard C in terms of overall response and it does not increase the overall incidence of severe infection. However, data on special groups of patients (for example, HIV positive subjects and HBV carriers) are lacking. In our opinion more studies are needed to explore the potential effect of R on silent and chronic viral infections.
authors.affiliation: National Institute for Infectious Diseases, INMI-Lazzaro Spallanzani Via Portuense, 292 00149 Rome, Italy. simone.lanini@inmi.it
authors.forename: Simone
authors.initials: S
authors.lastname: Lanini
authors.forename: Aoife C
authors.initials: AC
authors.lastname: Molloy
authors.forename: Paul E
authors.initials: PE
authors.lastname: Fine
authors.forename: Archibald G
authors.initials: AG
authors.lastname: Prentice
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Kibbler
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003141:Communicable Diseases / Q000453:epidemiology*; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D006801:Humans; D016867:Immunocompromised Host; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D008223:Lymphoma / Q000188:drug therapy*; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007155:Immunologic Factors; D000069283:Rituximab