Clinica Ematologica, Azienda Sanitaria-Universitaria Friuli Centrale (ASUFC), Udine, Italy.
IRCCS Ospedale San Raffaele, Milano, Italy.
Mycoses. 2020 Oct;63(10):1094-1100. doi: 10.1111/myc.13147. Epub 2020 Aug 23.
Acute myeloid leukaemia (AML) patients are at high risk of invasive aspergillosis (IA) after first induction chemotherapy (CHT). Although IA risk factors have been identified, few data are available on impact of IA, occurring during induction phase, on overall AML outcome.
The end point of this multicentre, case-control, study was to evaluate whether IA, occurring after first induction CHT, can affect treatment schedule and patient's outcome. We identified 40 AML patients (cases) who developed IA during first induction phase, 31 probable (77.5%) and 9 proven (22.5%). These cases were matched with a control group (80 AML) without IA, balanced according to age, type of CHT, AML characteristics and cytogenetic-molecular risk factors. The overall response rate to induction CHT was the same in the 2 groups. In the 40 cases with IA, the overall response rate to antifungal treatment was favourable (80%) but it was significantly affected by the achievement of leukaemia complete remission (CR) with induction CHT. In fact, in cases with AML responsive to induction CHT, responses of IA to antifungal therapy were 96% compared to 21% in cases of AML not responsive to induction treatment (P < .0001). The adherence to the schedule and full doses of CHT were reported in 35% of cases (14/40) and in 76% of controls (61/80) (P = .0001; OR 6.7; 95% CI 2.7-16.6). After first induction CHT, a significant higher number of cases (15/40; 37.5%) compared to controls (9/80; 11%) could not receive additional cycles of CHT (P = .0011, OR 4.8; 95% CI 1.9-12.3). The IA-related mortality was 22.5%. The median OS of cases was significantly worse than OS of controls with a difference of 12.3 months (12.1 vs 24.4 months, P = .04). However, the occurrence of IA during first induction phase did not have a significant impact on the OS of cases who achieved a CR of AML with induction CHT which are able to proceed, despite the IA, with their therapeutic program, achieving the same OS as the control group with AML in CR (P = ns).
These data show that IA during first induction CHT can delay the subsequent therapeutic program and has a significant impact on OS, specifically in AML patients who did not achieved a CR of AML with the first course of CHT.
急性髓系白血病（AML）患者在首次诱导化疗（CHT）后有发生侵袭性曲霉病（IA）的高风险。尽管已经确定了 IA 的危险因素，但关于诱导期发生的 IA 对 AML 总体结局的影响的数据很少。
本多中心病例对照研究的终点是评估首次诱导 CHT 后发生的 IA 是否会影响治疗方案和患者的结局。我们确定了 40 例在首次诱导期发生 IA 的 AML 患者（病例），其中 31 例为可能（77.5%），9 例为确诊（22.5%）。这些病例与无 IA 的对照组（80 例 AML）相匹配，根据年龄、CHT 类型、AML 特征和细胞遗传学-分子危险因素进行平衡。两组诱导 CHT 的总体反应率相同。在 40 例 IA 患者中，抗真菌治疗的总体反应率是有利的（80%），但与诱导 CHT 时 AML 完全缓解（CR）的获得显著相关。事实上，在对诱导 CHT 有反应的 AML 病例中，IA 对抗真菌治疗的反应率为 96%，而在对诱导治疗无反应的 AML 病例中为 21%（P<.0001）。在 35%的病例（14/40）和 76%的对照组（61/80）中报告了 CHT 方案和全剂量的遵守情况（P=.0001；OR 6.7；95%CI 2.7-16.6）。在首次诱导 CHT 后，与对照组（9/80；11%）相比，更多的病例（15/40；37.5%）无法接受额外的 CHT 周期（P=.0011，OR 4.8；95%CI 1.9-12.3）。IA 相关死亡率为 22.5%。病例的中位 OS 明显差于对照组，差异为 12.3 个月（12.1 与 24.4 个月，P=.04）。然而，首次诱导期发生的 IA 对接受诱导 CHT 后获得 AML CR 的病例的 OS 没有显著影响，这些病例能够继续其治疗方案，尽管发生了 IA，但仍能获得与 AML 获得 CR 的对照组相同的 OS（P=ns）。
这些数据表明，IA 在首次诱导 CHT 期间可能会延迟后续的治疗方案，并对 OS 产生显著影响，特别是在首次 CHT 未能获得 AML CR 的 AML 患者中。
