Morrison Vicki A
Section of Hematology/Oncology, Veterans Affairs Medical Center, University of Minnesota, Minneapolis, MN 55417, USA.
Clin Lymphoma Myeloma. 2009 Oct;9(5):365-70. doi: 10.3816/CLM.2009.n.071.
Infections continue to be a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL), as therapeutic advances have occurred over the past several decades. The pathogenesis of infection in these patients is multifactorial, including inherent immune defects related to the primary disease process, such as hypogammaglobulinemia, as well as therapy-related immunosuppression. A characteristic spectrum of infectious complications has been described for specific treatment agents. With chlorambucil, most infections are bacterial in origin, caused by common Gram-positive and -negative organisms. Recurrent infections are a hallmark, with the respiratory tract being the most common site of infection. The pathogenesis of infection with the purine analogues is related to the quantitative and qualitative T-cell abnormalities induced by these agents. Risk factors for infection identified in patients treated with fludarabine include advanced-stage disease, prior CLL therapy, response to therapy, elevated serum creatinine, hemoglobin < 12 g/dL, and decreased serum IgG. As compared with patients receiving chlorambucil, patients receiving fludarabine have more major infections and herpes virus infections. However, Pneumocystis, Aspergillus, and cytomegalovirus (CMV) infections are uncommon. The use of alemtuzumab is complicated by frequent opportunistic infections. CMV reactivation is especially problematic, occurring in 10%-25% of patients. For prevention of infection, the use of vaccinations and immunoglobulin replacement has been studied. Recommendations for prophylactic antimicrobial therapy have arisen from CLL treatment trials and anecdotal reports. As new treatment approaches are developed for CLL, one must consider not only the efficacy of these agents for disease response but also the effect on subsequent infectious complications. Infectious complications remain a significant cause of morbidity and mortality in patients with CLL. We will review the pathogenesis as well as the spectrum of infections in these patients. We will also discuss approaches to the prophylactic and therapeutic management of infections in these patients.
尽管在过去几十年里治疗方法取得了进展，但感染仍然是慢性淋巴细胞白血病（CLL）患者发病和死亡的主要原因。这些患者感染的发病机制是多因素的，包括与原发性疾病过程相关的固有免疫缺陷，如低丙种球蛋白血症，以及治疗相关的免疫抑制。已针对特定治疗药物描述了一系列特征性的感染并发症。使用苯丁酸氮芥时，大多数感染起源于细菌，由常见的革兰氏阳性和阴性生物体引起。反复感染是一个标志，呼吸道是最常见的感染部位。嘌呤类似物感染的发病机制与这些药物诱导的T细胞数量和质量异常有关。在接受氟达拉滨治疗的患者中确定的感染危险因素包括晚期疾病、既往CLL治疗、对治疗的反应、血清肌酐升高、血红蛋白<12 g/dL以及血清IgG降低。与接受苯丁酸氮芥治疗的患者相比，接受氟达拉滨治疗的患者有更多的严重感染和疱疹病毒感染。然而，肺孢子菌、曲霉菌和巨细胞病毒（CMV）感染并不常见。使用阿仑单抗会因频繁的机会性感染而变得复杂。CMV重新激活尤其成问题，发生在10%-25%的患者中。为预防感染，已对疫苗接种和免疫球蛋白替代疗法的使用进行了研究。预防性抗菌治疗的建议来自CLL治疗试验和轶事报道。随着为CLL开发新的治疗方法，人们不仅必须考虑这些药物对疾病反应的疗效，还必须考虑其对随后感染并发症的影响。感染并发症仍然是CLL患者发病和死亡的重要原因。我们将回顾这些患者感染的发病机制以及感染谱。我们还将讨论这些患者感染的预防和治疗管理方法。
