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

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 ch...

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Veröffentlicht in:European journal of haematology 2010-07, Vol.85 (1), p.58-64
Hauptverfasser: Klostergaard, Anja, Steffensen, Rudi, Møller, Jens K., Peterslund, Niels, Juhl-Christensen, Caroline, Mølle, Ingolf
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container_title European journal of haematology
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creator Klostergaard, Anja
Steffensen, Rudi
Møller, Jens K.
Peterslund, Niels
Juhl-Christensen, Caroline
Mølle, Ingolf
description 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.
doi_str_mv 10.1111/j.1600-0609.2010.01443.x
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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. 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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. 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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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>20331735</pmid><doi>10.1111/j.1600-0609.2010.01443.x</doi><tpages>7</tpages></addata></record>
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subjects acute leukaemia
acute myeloid leukaemia
Adolescent
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
CHIT-coding gene
chitotriosidase
Female
Genetic Predisposition to Disease
Gram-Negative Bacterial Infections - etiology
Gram-Negative Bacterial Infections - genetics
Gram-Negative Bacterial Infections - immunology
Gram-Positive Bacterial Infections - etiology
Gram-Positive Bacterial Infections - genetics
Gram-Positive Bacterial Infections - immunology
Hexosaminidases - genetics
Hexosaminidases - immunology
Humans
Immunity, Innate - genetics
infection
innate immune system
Leukemia, Myeloid, Acute - complications
Leukemia, Myeloid, Acute - drug therapy
Leukemia, Myeloid, Acute - genetics
Male
mannose-binding lectin
Mannose-Binding Lectin - genetics
Mannose-Binding Lectin - pharmacology
MBL-coding gene
Middle Aged
polymorphism
Polymorphism, Genetic
Recombinant Proteins - pharmacology
Risk Factors
Sepsis - etiology
Sepsis - genetics
Sepsis - immunology
Sepsis - prevention & control
Young Adult
title Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: No impact of chitotriosidase and mannose-binding lectin polymorphisms
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