Background Chronic lymphocytic leukemia (CLL) is a hematological malignancy characterized by immune dysfunction, which significantly contributes to increased morbidity and mortality due to infections. Summary Advancement in therapeutic strategies based on combination chemoimmunotherapy and targeted treatment have increased life expectancy for patients affected by CLL. However, mortality and morbidity due to infection showed no improvement over the last decades. Although therapy options are highly efficient in targeting leukemic cells, several studies highlighted the interactions of different treatments with the tumor microenvironment immune components, significantly impacting their clinical efficacy and fostering increased risk of infections. Key messages Given the profound immune dysfunction caused by CLL itself, treatment can thus represent a double-edged sword. Thus, it is essential to increase our understanding and awareness on how conventional therapies affect the disease-microenvironment-infection axis to ensure the best personalized strategy for each patient. This requires careful consideration of the advantages and disadvantages of efficient treatments, whether chemoimmunotherapy or targeted combinations, leading to risk of infectious complications. To this regard, our machine learning based algorithm CLL-TIM, currently implemented into the local electronic health record system for Eastern Denmark, aims at early identification of patients at high risk of serious infections (PreVent-ACaLL; NCT03868722). We here review strategies for management of immune dysfunction and infections in CLL.

中文翻译：

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免疫功能障碍和感染 - CLL 与治疗之间的相互作用对当前治疗模式和未满足需求的反思。

背景慢性淋巴细胞白血病（CLL）是一种以免疫功能障碍为特征的血液恶性肿瘤，它显着增加了感染引起的发病率和死亡率。摘要 基于联合化学免疫疗法和靶向治疗的治疗策略的进步提高了 CLL 患者的预期寿命。然而，过去几十年来，感染引起的死亡率和发病率没有改善。尽管治疗方案在靶向白血病细胞方面非常有效，但一些研究强调了不同治疗方法与肿瘤微环境免疫成分的相互作用，显着影响其临床疗效并增加感染风险。关键信息 鉴于 CLL 本身引起的严重免疫功能障碍，治疗可能是一把双刃剑。因此，有必要提高我们对传统疗法如何影响疾病-微环境-感染轴的理解和认识，以确保为每位患者提供最佳的个性化策略。这需要仔细考虑有效治疗的优点和缺点，无论是化学免疫疗法还是靶向组合，都会导致感染并发症的风险。为此，我们基于机器学习的算法 CLL-TIM 目前已应用于丹麦东部的当地电子健康记录系统，旨在及早识别严重感染高风险的患者（PreVent-ACaLL；NCT03868722）。我们在此回顾 CLL 免疫功能障碍和感染的治疗策略。