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

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.

Effects of Mannose-Binding Lectin Polymorphisms on Irinotecan-Induced Febrile Neutropenia

“…Another interesting analysis showed a trend toward more grade 4 neutropenic infections in multiple myeloma patients carrying the high MBL-producing wild-type exon polymorphism [14]. Interestingly, Klostergaard et al [48] found a significantly higher incidence of Gram-negative blood cultures in high MBL genotypes, which could explain why we found a higher incidence of febrile neutropenia in high MBL genotypes and positive blood cultures of only Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) in our study.…”

<i>MBL2</i> Gene Polymorphism and the Association with Neonatal Sepsis in Egyptian Neonates, a Case Control Study

“…However our result inconsistent with study by Hellemann et al [31] in critically ill patients admitted to an intensive care, which reported an association of low MBL2 O/O genotype with an increased incidence of Gram-positive infections. Other study performed by Klostergaard et al [32] didn't find any association between MBL2 polymorphism and the type of bacterial sepsis. The diversity between the different studies may be explained by fact that MBL also acts as a scavenger molecule in maintaining internal tissue homeostasis.…”

Gene Polymorphisms and Febrile Neutropenia in Acute Leukemia—No Association with IL-4, CCR-5, IL-1RA, but the MBL-2, ACE, and TLR-4 Are Associated with the Disease in Turkish Patients: A Preliminary Study

“…However, correlation was determined between MBL-2 polymorphisms and the duration of febrile episodes in our study. Some studies found no differences between the frequency of infections and MBL-2 GPs (Frakking et al, 2009;Klostergaard et al, 2010). The second major part of our discussion is on the effect of MBL-2 variants on bacterial subclasses.…”

“…There are some articles that support the role of different GPs in FN (Vekemens et al, 2007). It is now nearly four decades since the relationship between the degree of neutropenia and the risk of bacterial and fungal infections was first recognized in patients treated for cancer (Bucaneve et al, 2005;Vekemens et al, 2007;Klostergaard et al, 2010;Roongpoovapatr and Suankratay, 2010). Infections were noted to be worse during relapse of the underlying disease and the failure of leukocytes to recover following an infection has a very poor prognosis.…”

“…The body's response to bacterial infection requires first, recognition of the presence of pathogen-associated bacterial products through receptors (Klostergaard et al, 2010). Polymorphisms in genes coding for proteins involved in the recognition of bacterial pathogens (Toll-like receptor 4 , mannose-binding lectin 2 [MBL-2], etc.)…”