title: The High Prevalence of Functional Complement Defects Induced by Chemotherapy.
abstract: BACKGROUND
  To date, oncology patients are more dependent on non-cellular host defense against pathogens due to intensive (chemo)therapy-related bone marrow suppression. Since data on complement functionality in oncology patients are limited, we aimed to investigate the innate complement function in relation to the type of malignancy and therapy in a longitudinal cohort of patients.
  
  
  METHODS
  A large single-center, prospective non-intervention study was conducted, in which blood samples were taken from patients before, during, and after treatment with chemotherapy and/or subsequent admittance for (febrile) neutropenia.
  
  
  RESULTS
  Analysis of 48 patients showed a high percentage of defects in complement activity of the alternative pathway (19.1%), the classical pathway (4.3%), or both (42.6%).Post hocanalysis of six different treatment protocols with more than three patients each showed distinct effects of specific therapies. Whereas patients treated according to the Ewing, EpSSG-rhabdomyosarcoma, or SIOP CNS germ cell tumor protocol showed no defects, patients treated according to the ALL-11 (leukemia), the EURAMOS I (osteosarcoma), or the ACNS (medulloblastoma) protocols showed an almost universal reduction in complement function. Although we could not explain the reduced complement functionality under all conditions, a strong effect was observed following high-dose methotrexate or ifosfamide.
  
  
  CONCLUSIONS
  Acquired complement defects were commonly observed in more than 50% of oncology patients, some of which associated with certain chemotherapeutic drugs. Additional studies are needed to determine the clinical and therapeutic context of complement defects and their possible effect on treatment outcome or the increased risk of infection.
authors: Sanquin Research and Landsteiner Laboratory AMC, Department of Immunopathology, University of Amsterdam, Amsterdam, Netherlands; Academic Medical Center (AMC), Emma Children's Hospital, University of Amsterdam, Amsterdam, Netherlands.
authors: Mischa P
authors: MP
authors: Keizer
authors: Sanquin Research and Landsteiner Laboratory AMC, Department of Immunopathology, University of Amsterdam , Amsterdam , Netherlands.
authors: Angela M
authors: AM
authors: Kamp
authors: Sanquin Research and Landsteiner Laboratory AMC, Department of Immunopathology, University of Amsterdam , Amsterdam , Netherlands.
authors: Cathelijn
authors: C
authors: Aarts
authors: Sanquin Research and Landsteiner Laboratory AMC, Department of Blood Cell Research, University of Amsterdam , Amsterdam , Netherlands.
authors: Judy
authors: J
authors: Geisler
authors: Academic Medical Center (AMC), Emma Children's Hospital, University of Amsterdam , Amsterdam , Netherlands.
authors: Huib N
authors: HN
authors: Caron
authors: Academic Medical Center (AMC), Emma Children's Hospital, University of Amsterdam , Amsterdam , Netherlands.
authors: Marianne D
authors: MD
authors: van de Wetering
authors: Sanquin Research and Landsteiner Laboratory AMC, Department of Immunopathology, University of Amsterdam , Amsterdam , Netherlands.
authors: Diana
authors: D
authors: Wouters
authors: Academic Medical Center (AMC), Emma Children's Hospital, University of Amsterdam, Amsterdam, Netherlands; Sanquin Research and Landsteiner Laboratory AMC, Department of Blood Cell Research, University of Amsterdam, Amsterdam, Netherlands.
authors: Taco W
authors: TW
authors: Kuijpers
keywords: complement system; methotrexate; oncology; therapeutic effect; transient defects