Low concentrations of the blood protein mannose-binding lectin (MBL) are associated with prolonged fever in cancer patients treated with chemotherapy, conclude authors of two studies published in this week’s issue of THE LANCET. Genetic identification of patients with low MBL concentrations and the potential for MBL-replacement therapy could represent a step forward in reducing illness and death for cancer patients.
More than one in 600 children in industrialised countries develop a malignancy in the first 15 years of life. Although there have been major advances in therapy, most children have chemotherapy-associated complications, the commonest of which is infection; 65% of childhood deaths from myeloid leukaemia, for example, are associated with chemotherapy-related infection. MBL plays an important role in the immune system and could influence susceptibility to infection for individuals treated with chemotherapy. Nigel Klein and colleagues from the Institute for Child Health, London, UK, investigated the extent of chemotherapy-related infection in relation to MBL concentrations among children with cancer.
The frequency, duration, and causes of fever relating to a low concentration of white blood cells (common after chemotherapy), and MBL concentrations were recorded for 100 children with cancer at Great Ormond Street Hospital, London, UK. Children with low MBL concentrations had prolonged infections compared with those with normal MBL concentrations within 6 months of cancer diagnosis (20.5 days compared with 10 days). The investigators conclude that this finding implies that MBL infusions could represent a new therapeutic approach which would aid the management of chemotherapy-induced complications for children with cancer.
In a research letter (p 637), Jens Jensenius and colleagues from Aarhus University, Denmark, showed a significant association between low concentrations of MBL and serious infections related to chemotherapy in a study of 54 adult patients. The investigators comment that increasing concentrations of MBL in patients having or about to have chemotherapy could reduce susceptibility to infection.
In an accompanying Commentary (p 598), Alan Ezekowitz from Massachusetts General Hospital, Boston, USA, states that the genetic identification of individuals with low MBL concentrations has clinical implications for the treatment of chemotherapy-related infection. He concludes: “Taken together these studies indicate that there is a threshold level of MBL that correlates with an increased risk of infection. Nevertheless, the small sample size of the groups studied and the lack of clear stratification of patients into high and low risk groups means the need for further analysis with better defined populations, larger sample size, and more refined risk stratification. Such studies herald in a new era of defining risk in febrile neutropenia, in which premorbid susceptibility to infection should be assessed…MBL haplotyping in febrile neutropenia may therefore be just the first step in the development of a much more comprehensive profile of susceptibility to infection in febrile neutropenia. In the longer term, replacement therapy is a tantalising possibility.”
Contact: Dr Nigel J Klein,c/o Stephen Cox, Chief Press Officer, Great Ormond St Hospital for Children NHS Trust and the Institute for Child Health, 40-41 Queens Square, London WC1N 3AJ, UK; T) 44-20-7829-8671; F) 44-20-7813-7718; E) N.Klein@ich.ucl.ac.uk
Professor J C Jensenius, Department of Medical Microbiology and Immunology, Institute of Medical Microbiology and Immunology, Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark; T) 45-8942-1775; F) 45-8619-6128; E) jensenius@svfcd.au.dk
Dr Alan Ezekowitz, Department of Paediatrics,Massachusetts General Hospital,Boston,MA 02114,USA; T) 1-617-724-2911; F) 1-617-726-4466;E) ezekowitz.alan@mgh.harvard.edu
Journal
The Lancet