Department of Haematology, Aarhus University Hospital, Aarhus C, Denmark.
Eur J Haematol. 2010 Jul;85(1):58-64. doi: 10.1111/j.1600-0609.2010.01443.x. Epub 2010 Mar 12.
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.
在接受急性髓细胞白血病(AML)化疗的患者中,感染常常导致显著的发病率。壳三糖苷酶(CHIT)和甘露糖结合凝集素(MBL)是固有免疫系统的一部分。CHIT 编码基因(CHIT1)的多态性可能与 AML 患儿的革兰氏阴性菌败血症有关,而 MBL 编码基因(MBL2)的多态性似乎会改变几个患者群体的感染风险。本研究旨在探讨 CHIT1、MBL2 多态性与接受大剂量化疗治疗 AML 的成年患者败血症之间的可能关联。我们纳入了 190 名接受 526 个化疗周期治疗的患者。随访期为 AML 诊断后 6 个月。未使用预防性抗生素。我们确定了 604 次发热发作和 246 次败血症发作。32 名患者(17%)因感染而死亡或感染是死亡的主要伴随因素。未发现 CHIT1 多态性与败血症(P=0.85)或败血症引起的死亡(P=0.14)之间存在显著关联。此外,未观察到 MBL2 多态性与败血症(P=0.76)或败血症引起的死亡(P=0.24)之间存在显著关联。化疗后严重且持久的中性粒细胞减少症和粘膜炎可能解释了为什么 MBL 系统不能预防 AML 患者的败血症。用重组 MBL 进行替代治疗不太可能降低 AML 患者败血症的风险。