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Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: No impact of chitotriosidase and mannose-binding lectin polymorphisms

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Abstract

Infections after chemotherapy often cause significant morbidity in patients with acute myeloid leukaemia (AML). Chitotriosidase (CHIT) and mannose-binding lectin (MBL) are part of the innate immune system. Polymorphism in the CHIT-coding gene (CHIT1) may be associated with Gram-negative sepsis in children with AML, and polymorphism in the MBL-coding gene (MBL2) seems to modify the risk of infections in several patient groups. The purpose of this study was to investigate the possible associations between polymorphisms in CHIT1, MBL2 and sepsis in adult patients treated with high-dose chemotherapy for AML. We included 190 patients treated with 526 cycles of chemotherapy. The follow-up period was 6 months from the diagnosis of AML. Prophylactic antibiotics were not used. We identified 604 febrile episodes with 246 episodes of sepsis. Thirty-two patients (17%) either died from infection or infection was a major concomitant factor for death. No significant associations between CHIT1 polymorphism and sepsis (P = 0.85) or death caused by sepsis (P = 0.14) were found. Furthermore, no significant associations between MBL2 polymorphism and sepsis (P = 0.76) or death caused by sepsis (P = 0.24) were observed. The severe and long-lasting neutropenia and mucositis after chemotherapy may explain why the MBL system does not protect against sepsis in patients with AML. Replacement therapy with recombinant MBL is not likely to decrease the risk of sepsis in patients with AML.
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Keywords: CHIT-coding gene; MBL-coding gene; acute leukaemia; acute myeloid leukaemia; chitotriosidase; infection; innate immune system; mannose-binding lectin; polymorphism

Document Type: Research Article

Affiliations: 1: Department of Haematology, Aarhus University Hospital, Aarhus C, Denmark 2: Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark 3: Department of Clinical Microbiology, Aarhus University Hospital, Aarhus C, Denmark

Publication date: July 1, 2010

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