Anja Klostergaard, Department of Haematology, Aarhus University Hospital, Tage-Hansensgade 2, 8000 Aarhus C, Denmark. Tel: 0045 89497551; Fax: 0045 89497599; e-mail: [email protected]

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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.

References

1 Bucaneve G, Micozzi A, Menichetti F, et al. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med 2005; 353: 977–87.
10.1056/NEJMoa044097
CAS PubMed Web of Science® Google Scholar
2 Engels EA, Lau J, Barza M. Efficacy of quinolone prophylaxis in neutropenic cancer patients: a meta-analysis. J Clin Oncol 1998; 16: 1179–87.
10.1200/JCO.1998.16.3.1179
CAS PubMed Web of Science® Google Scholar
3 Gafter-Gvili A, Fraser A, Paul M, Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med 2005; 142: 979–95.
10.7326/0003-4819-142-12_Part_1-200506210-00008
PubMed Web of Science® Google Scholar
4 Molle I, Peterslund NA, Thiel S, Steffensen R. MBL2 polymorphism and risk of severe infections in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation. Bone Marrow Transplant 2006; 38: 555–60.
10.1038/sj.bmt.1705466
CAS PubMed Web of Science® Google Scholar
5 Neth O, Hann I, Turner MW, Klein NJ. Deficiency of mannose-binding lectin and burden of infection in children with malignancy: a prospective study. Lancet 2001; 358: 614–8.
10.1016/S0140-6736(01)05776-2
CAS PubMed Web of Science® Google Scholar
6 Lehrnbecher T, Bernig T, Hanisch M, Koehl U, Behl M, Reinhardt D, Creutzig U, Klingebiel T, Chanock SJ, Schwabe D. Common genetic variants in the interleukin-6 and chitotriosidase genes are associated with the risk for serious infection in children undergoing therapy for acute myeloid leukemia. Leukemia 2005; 19: 1745–50.
10.1038/sj.leu.2403922
CAS PubMed Web of Science® Google Scholar
7 Vekemans M, Robinson J, Georgala A, et al. Low mannose-binding lectin concentration is associated with severe infection in patients with hematological cancer who are undergoing chemotherapy. Clin Infect Dis 2007; 44: 1593–601.
10.1086/518171
CAS PubMed Web of Science® Google Scholar
8 Choi EH, Zimmerman PA, Foster CB, Zhu S, Kumaraswami V, Nutman TB, Chanock SJ. Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India. Genes Immun 2001; 2: 248–53.
10.1038/sj.gene.6363767
CAS PubMed Web of Science® Google Scholar
9 Choi EH, Taylor JG, Foster CB, Walsh TJ, Anttila VJ, Ruutu T, Palotie A, Chanock SJ. Common polymorphisms in critical genes of innate immunity do not contribute to the risk for chronic disseminated candidiasis in adult leukemia patients. Med Mycol 2005; 43: 349–53.
10.1080/13693780412331282322
PubMed Web of Science® Google Scholar
10 Boot RG, Renkema GH, Verhoek M, Strijland A, Bliek J, De Meulemeester TM, Mannens MM, Aerts JM. The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem 1998; 273: 25680–5.
10.1074/jbc.273.40.25680
CAS PubMed Web of Science® Google Scholar
11 Malaguarnera L, Simpore J, Prodi DA, Angius A, Sassu A, Persico I, Barone R, Musumeci S. A 24-bp duplication in exon 10 of human chitotriosidase gene from the sub-Saharan to the Mediterranean area: role of parasitic diseases and environmental conditions. Genes Immun 2003; 4: 570–4.
10.1038/sj.gene.6364025
CAS PubMed Web of Science® Google Scholar
12 Gordon AC, Waheed U, Hansen TK, Hitman GA, Garrard CS, Turner MW, Klein NJ, Brett SJ, Hinds CJ. Mannose-binding lectin polymorphisms in severe sepsis: relationship to levels, incidence, and outcome. Shock 2006; 25: 88–93.
10.1097/01.shk.0000186928.57109.8d
CAS PubMed Web of Science® Google Scholar
13 Garred P, Strom J, Quist L, Taaning E, Madsen HO. Association of mannose-binding lectin polymorphisms with sepsis and fatal outcome, in patients with systemic inflammatory response syndrome. J Infect Dis 2003; 188: 1394–403.
10.1086/379044
CAS PubMed Web of Science® Google Scholar
14 Neth OW, Bacher U, Das P, et al. Influence of mannose-binding lectin genotypes and serostatus in Allo-SCT: analysis of 131 recipients and donors. Bone Marrow Transplant 2010; 45: 13–9.
10.1038/bmt.2009.90
CAS PubMed Web of Science® Google Scholar
15 Kilpatrick DC, Stewart K, Allan EK, McLintock LA, Holyoake TL, Turner ML. Successful haemopoietic stem cell transplantation does not correct mannan-binding lectin deficiency. Bone Marrow Transplant 2005; 35: 179–81.
10.1038/sj.bmt.1704746
CAS PubMed Web of Science® Google Scholar
16 Mullighan CG, Heatley SL, Danner S, et al. Mannose-binding lectin status is associated with risk of major infection following myeloablative sibling allogeneic hematopoietic stem cell transplantation. Blood 2008; 112: 2120–8.
10.1182/blood-2007-07-100222
CAS PubMed Web of Science® Google Scholar
17 Mullighan CG, Heatley S, Doherty K, et al. Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation. Blood 2002; 99: 3524–9.
10.1182/blood.V99.10.3524
CAS PubMed Web of Science® Google Scholar
18 Bergmann OJ, Christiansen M, Laursen I, Bang P, Hansen NE, Ellegaard J, Koch C, Andersen V. Low levels of mannose-binding lectin do not affect occurrence of severe infections or duration of fever in acute myeloid leukaemia during remission induction therapy. Eur J Haematol 2003; 70: 91–7.
10.1034/j.1600-0609.2003.00012.x
PubMed Web of Science® Google Scholar
19 Madsen HO, Garred P, Thiel S, Kurtzhals JA, Lamm LU, Ryder LP, Svejgaard A. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 1995; 155: 3013–20.
10.4049/jimmunol.155.6.3013
CAS PubMed Web of Science® Google Scholar
20 Petersen SV, Thiel S, Jensenius JC. The mannan-binding lectin pathway of complement activation: biology and disease association. Mol Immunol 2001; 38: 133–49.
10.1016/S0161-5890(01)00038-4
CAS PubMed Web of Science® Google Scholar
21 Steffensen R, Thiel S, Varming K, Jersild C, Jensenius JC. Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers. J Immunol Methods 2000; 241: 33–42.
10.1016/S0022-1759(00)00198-8
CAS PubMed Web of Science® Google Scholar
22 Garred P, Thiel S, Madsen HO, Ryder LP, Jensenius JC, Svejgaard A. Gene frequency and partial protein characterization of an allelic variant of mannan binding protein associated with low serum concentrations. Clin Exp Immunol 1992; 90: 517–21.
10.1111/j.1365-2249.1992.tb05876.x
CAS PubMed Web of Science® Google Scholar
23 Steffensen R, Hoffmann K, Varming K. Rapid genotyping of MBL2 gene mutations using real-time PCR with fluorescent hybridisation probes. J Immunol Methods 2003; 278: 191–9.
10.1016/S0022-1759(03)00190-X
CAS PubMed Web of Science® Google Scholar
24 Olesen HV, Jensenius JC, Steffensen R, Thiel S, Schiotz PO. The mannan-binding lectin pathway and lung disease in cystic fibrosis--disfunction of mannan-binding lectin-associated serine protease 2 (MASP-2) may be a major modifier. Clin Immunol 2006; 121: 324–31.
10.1016/j.clim.2006.08.014
CAS PubMed Web of Science® Google Scholar
25 Petersen KA, Matthiesen F, Agger T, Kongerslev L, Thiel S, Cornelissen K, Axelsen M. Phase I safety, tolerability, and pharmacokinetic study of recombinant human mannan-binding lectin. J Clin Immunol 2006; 26: 465–75.
10.1007/s10875-006-9037-z
CAS PubMed Web of Science® Google Scholar
26 Van Hoeyveld E, Houtmeyers F, Massonet C, Moens L, Van Ranst M, Blanckaert N, Bossuyt X. Detection of single nucleotide polymorphisms in the mannose-binding lectin gene using minor groove binder-DNA probes. J Immunol Methods 2004; 287: 227–30.
10.1016/j.jim.2004.01.025
CAS PubMed Web of Science® Google Scholar
27 Molle I, Steffensen R, Thiel S, Peterslund NA. Chemotherapy-related infections in patients with multiple myeloma: associations with mannan-binding lectin genotypes. Eur J Haematol 2006; 77: 19–26.
10.1111/j.1600-0609.2006.00669.x
CAS PubMed Web of Science® Google Scholar
28 Lehrnbecher T, Varwig D, Kaiser J, Reinhardt D, Klingebiel T, Creutzig U. Infectious complications in pediatric acute myeloid leukemia: analysis of the prospective multi-institutional clinical trial AML-BFM 93. Leukemia 2004; 18: 72–7.
10.1038/sj.leu.2403188
CAS PubMed Web of Science® Google Scholar
29 Klein NJ, Kilpatrick DC. Is there a role for mannan/mannose-binding lectin (MBL) in defence against infection following chemotherapy for cancer? Clin Exp Immunol 2004; 138: 202–4.
10.1111/j.1365-2249.2004.02604.x
CAS PubMed Web of Science® Google Scholar
30 Shang SQ, Chen GX, Shen J, Yu XH, Wang KY. The binding of MBL to common bacteria in infectious diseases of children. J Zhejiang Univ Sci B 2005; 6: 53–6.
10.1631/jzus.2005.B0053
PubMed Google Scholar
31 Neth O, Jack DL, Dodds AW, Holzel H, Klein NJ, Turner MW. Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition. Infect Immun 2000; 68: 688–93.
10.1128/IAI.68.2.688-693.2000
CAS PubMed Web of Science® Google Scholar

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Volume85, Issue1

July 2010

Pages 58-64

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

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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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