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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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. Replacement therapy with recombinant MBL is not likely to decrease the risk of sepsis in patients with AML.</description><identifier>ISSN: 0902-4441</identifier><identifier>EISSN: 1600-0609</identifier><identifier>DOI: 10.1111/j.1600-0609.2010.01443.x</identifier><identifier>PMID: 20331735</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>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</subject><ispartof>European journal of haematology, 2010-07, Vol.85 (1), p.58-64</ispartof><rights>2010 John Wiley & Sons A/S</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4383-1d2f4d7d6682ff29547acb94e3e165c2f35f15a9e95627fd6b9c4e8abe0580b73</citedby><cites>FETCH-LOGICAL-c4383-1d2f4d7d6682ff29547acb94e3e165c2f35f15a9e95627fd6b9c4e8abe0580b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1600-0609.2010.01443.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1600-0609.2010.01443.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20331735$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Klostergaard, Anja</creatorcontrib><creatorcontrib>Steffensen, Rudi</creatorcontrib><creatorcontrib>Møller, Jens K.</creatorcontrib><creatorcontrib>Peterslund, Niels</creatorcontrib><creatorcontrib>Juhl-Christensen, Caroline</creatorcontrib><creatorcontrib>Mølle, Ingolf</creatorcontrib><title>Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: No impact of chitotriosidase and mannose-binding lectin polymorphisms</title><title>European journal of haematology</title><addtitle>Eur J Haematol</addtitle><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.</description><subject>acute leukaemia</subject><subject>acute myeloid leukaemia</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols</subject><subject>CHIT-coding gene</subject><subject>chitotriosidase</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Gram-Negative Bacterial Infections - etiology</subject><subject>Gram-Negative Bacterial Infections - genetics</subject><subject>Gram-Negative Bacterial Infections - immunology</subject><subject>Gram-Positive Bacterial Infections - etiology</subject><subject>Gram-Positive Bacterial Infections - genetics</subject><subject>Gram-Positive Bacterial Infections - immunology</subject><subject>Hexosaminidases - genetics</subject><subject>Hexosaminidases - immunology</subject><subject>Humans</subject><subject>Immunity, Innate - genetics</subject><subject>infection</subject><subject>innate immune system</subject><subject>Leukemia, Myeloid, Acute - complications</subject><subject>Leukemia, Myeloid, Acute - drug therapy</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Male</subject><subject>mannose-binding lectin</subject><subject>Mannose-Binding Lectin - genetics</subject><subject>Mannose-Binding Lectin - pharmacology</subject><subject>MBL-coding gene</subject><subject>Middle Aged</subject><subject>polymorphism</subject><subject>Polymorphism, Genetic</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Risk Factors</subject><subject>Sepsis - etiology</subject><subject>Sepsis - genetics</subject><subject>Sepsis - immunology</subject><subject>Sepsis - prevention & control</subject><subject>Young Adult</subject><issn>0902-4441</issn><issn>1600-0609</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkd-O1CAUhxujccfVVzDcedURCoVi4oWZ7B_NZkzWNV4SCqc7zLalQqvT1_CJpc46t8oN5JzvOyfhl2WI4DVJ5-1-TTjGOeZYrgucqpgwRteHJ9nq1HiarbDERc4YI2fZixj3GONCEvE8OyswpUTQcpX9-gJDdBG5HmkzjYC6GVrvLGphetDQOY0GPTrox4gCGHA_XH-Pdu5-l1sfAZkddH7cQdDD_A5tPXLdoM2IfJNabvRjcD46qxOqe4s63fdJy2vX22VQC2ZMqwffzp0Pw87FLr7MnjW6jfDq8T7Pvl5e3G2u85vPVx83H25yw2hFc2KLhllhOa-KpilkyYQ2tWRAgfDSFA0tG1JqCbLkhWgsr6VhUOkacFnhWtDz7M1x7hD89wniqDoXDbSt7sFPUQnG09cyKf9NUiplWbEqkdWRNMHHGKBRQ3CdDrMiWC3Rqb1aElJLQmqJTv2JTh2S-vpxyVR3YE_i36wS8P4I_HQtzP89WF18ul5eyc-PvosjHE6-Dg-KCypK9W17pe424nZbbLi6pb8BsEO5zQ</recordid><startdate>201007</startdate><enddate>201007</enddate><creator>Klostergaard, Anja</creator><creator>Steffensen, Rudi</creator><creator>Møller, Jens K.</creator><creator>Peterslund, Niels</creator><creator>Juhl-Christensen, Caroline</creator><creator>Mølle, Ingolf</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>201007</creationdate><title>Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: No impact of chitotriosidase and mannose-binding lectin polymorphisms</title><author>Klostergaard, Anja ; Steffensen, Rudi ; Møller, Jens K. ; Peterslund, Niels ; Juhl-Christensen, Caroline ; Mølle, Ingolf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4383-1d2f4d7d6682ff29547acb94e3e165c2f35f15a9e95627fd6b9c4e8abe0580b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>acute leukaemia</topic><topic>acute myeloid leukaemia</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols</topic><topic>CHIT-coding gene</topic><topic>chitotriosidase</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Gram-Negative Bacterial Infections - etiology</topic><topic>Gram-Negative Bacterial Infections - genetics</topic><topic>Gram-Negative Bacterial Infections - immunology</topic><topic>Gram-Positive Bacterial Infections - etiology</topic><topic>Gram-Positive Bacterial Infections - genetics</topic><topic>Gram-Positive Bacterial Infections - immunology</topic><topic>Hexosaminidases - genetics</topic><topic>Hexosaminidases - immunology</topic><topic>Humans</topic><topic>Immunity, Innate - genetics</topic><topic>infection</topic><topic>innate immune system</topic><topic>Leukemia, Myeloid, Acute - complications</topic><topic>Leukemia, Myeloid, Acute - drug therapy</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Male</topic><topic>mannose-binding lectin</topic><topic>Mannose-Binding Lectin - genetics</topic><topic>Mannose-Binding Lectin - pharmacology</topic><topic>MBL-coding gene</topic><topic>Middle Aged</topic><topic>polymorphism</topic><topic>Polymorphism, Genetic</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Risk Factors</topic><topic>Sepsis - etiology</topic><topic>Sepsis - genetics</topic><topic>Sepsis - immunology</topic><topic>Sepsis - prevention & control</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Klostergaard, Anja</creatorcontrib><creatorcontrib>Steffensen, Rudi</creatorcontrib><creatorcontrib>Møller, Jens K.</creatorcontrib><creatorcontrib>Peterslund, Niels</creatorcontrib><creatorcontrib>Juhl-Christensen, Caroline</creatorcontrib><creatorcontrib>Mølle, Ingolf</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>European journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klostergaard, Anja</au><au>Steffensen, Rudi</au><au>Møller, Jens K.</au><au>Peterslund, Niels</au><au>Juhl-Christensen, Caroline</au><au>Mølle, Ingolf</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: No impact of chitotriosidase and mannose-binding lectin polymorphisms</atitle><jtitle>European journal of haematology</jtitle><addtitle>Eur J Haematol</addtitle><date>2010-07</date><risdate>2010</risdate><volume>85</volume><issue>1</issue><spage>58</spage><epage>64</epage><pages>58-64</pages><issn>0902-4441</issn><eissn>1600-0609</eissn><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.</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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