PDF(Pubmed)
Abstract：
Invasive fungal diseases (IFDs) still represent a relevant cause of mortality in patients affected by hematological malignancies, especially acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) undergoing remission induction chemotherapy, and in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Mold-active antifungal prophylaxis (MAP) has been established as a standard of care. However, breakthrough IFDs (b-IFDs) have emerged as a significant issue, particularly invasive aspergillosis and non-Aspergillus invasive mold diseases. Here, we perform a narrative review, discussing the major advances of the last decade on prophylaxis, the diagnosis of and the treatment of IFDs in patients with high-risk neutropenic fever undergoing remission induction chemotherapy for AML/MDS and allo-HSCT. Then, we present our single-center retrospective experience on b-IFDs in 184 AML/MDS patients undergoing high-dose chemotherapy while receiving posaconazole (n = 153 induction treatments, n = 126 consolidation treatments, n = 60 salvage treatments). Six cases of probable/proven b-IFDs were recorded in six patients, with an overall incidence rate of 1.7% (6/339), which is in line with the literature focused on MAP with azoles. The incidence rates (IRs) of b-IFDs (95% confidence interval (95% CI), per 100 person years follow-up (PYFU)) were 5.04 (0.47, 14.45) in induction (n = 2), 3.25 (0.0013, 12.76) in consolidation (n = 1) and 18.38 (3.46, 45.06) in salvage chemotherapy (n = 3). Finally, we highlight the current challenges in the field of b-IFDs; these include the improvement of diagnoses, the expanding treatment landscape of AML with molecular targeted drugs (and related drug-drug interactions with azoles), evolving transplantation techniques (and their related impacts on IFDs\' risk stratification), and new antifungals and their features (rezafungin and olorofim).
摘要：
侵袭性真菌病（IFD）仍然是血液系统恶性肿瘤患者死亡的相关原因。尤其是接受缓解诱导化疗的急性髓系白血病（AML）和骨髓增生异常综合征（MDS），以及异基因造血干细胞移植（allo-HSCT）接受者。霉菌活性抗真菌预防（MAP）已被确立为护理标准。然而,突破性的IFD(B-IFD)已经成为一个重要问题，特别是侵袭性曲霉病和非曲霉侵袭性霉菌病。这里,我们进行叙述性审查，讨论过去十年在预防方面的重大进展，在接受AML/MDS和allo-HSCT缓解诱导化疗的高危中性粒细胞减少症患者中，IFDs的诊断和治疗。然后，我们介绍了184例接受泊沙康唑同时接受大剂量化疗的AML/MDS患者的单中心b-IFDs回顾性研究(n=153诱导治疗,n=126个巩固治疗，n=60次抢救处理)。在6例患者中记录了6例可能/证实的b-IFD，总发病率为1.7%(6/339)，这与聚焦于唑类MAP的文献一致。b-IFD的发生率(IR)(95%置信区间(95%CI)，每100人年随访（PYFU））的诱导率为5.04（0.47，14.45）（n=2），巩固（n=1）为3.25（0.0013，12.76），挽救性化疗（n=3）为18.38（3.46，45.06）。最后,我们强调目前在b-IFD领域的挑战;这些包括改善诊断，使用分子靶向药物（以及与唑类药物相关的药物-药物相互作用）扩大AML的治疗范围，不断发展的移植技术(及其对IFD风险分层的相关影响)，和新的抗真菌药及其特征（rezafungin和olorofim）。
