Penack Olaf, Tridello Gloria, Salmenniemi Urpu, Martino Rodrigo, Khanna Nina, Perruccio Katia, Fagioli Franca, Richert-Przygonska Monika, Labussière-Wallet Hélène, Maertens Johan, Jubert Charlotte, Aljurf Mahmoud, Pichler Herbert, Kriván Gergely, Kunadt Desiree, Popova Marina, Gabriel Melissa, Calore Elisabetta, Blau Igor Wolfgang, Benedetti Fabio, Itäla-Remes Maija, de Kort Elizabeth, Russo Domenico, Faraci Maura, Ménard Anne-Lise, von dem Borne Peter, Poiré Xavier, Yesilipek Akif, Gozdzik Jolanta, Yeğin Zeynep Arzu, Yañez Lucrecia, Facchini Luca, Van Gorkom Gwendolyn, Thurner Lorenz, Kocak Ulker, Sampol Antònia, Zuckerman Tsila, Bierings Marc, Mielke Stephan, Ciceri Fabio, Wendel Lotus, Knelange Nina, Mikulska Malgorzata, Averbuch Dina, Styczynski Jan, Camara Rafael de la, Cesaro Simone
Medizinische Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie, Berlin, Germany.
EBMT Leiden Study Unit, Leiden, the Netherlands.
EClinicalMedicine. 2023 Dec 22;67:102393. doi: 10.1016/j.eclinm.2023.102393. eCollection 2024 Jan.
Infections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed.
We performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints.
1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2-26.0) and 11.2% (9.6-13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2-3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3-68.9] vs. 70.4 [67.9-72.8]; multivariate HR 1.5 [1.1-2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8-77.4] vs. 79.0% [76.7-81.1]; multivariate HR 1.7 [1.1-2.5]; p = 0.01).
Pre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure.
There was no external funding source for this study.
感染是急性白血病治疗期间死亡的主要原因，侵袭性曲霉病（IA）是一个主要问题。异基因干细胞移植（alloSCT）是一种标准疗法，通常是白血病患者唯一的救命程序。过去，alloSCT后出现的严重免疫缺陷导致IA相关死亡率很高。因此，IA患者在历史上被认为不适合进行移植。最近，包括新型抗真菌药物在内的抗真菌治疗有所改善。结果，更多患有IA的白血病患者正在接受alloSCT。其结局尚未得到前瞻性评估。
我们对接受alloSCT的急性白血病患者进行了一项前瞻性研究，以分析既往可能或确诊的IA病史（移植前IA）的影响。主要终点是1年无复发生存率（NRM）。无病生存率和总生存率作为次要终点进行分析。
2016年至2021年期间共纳入1439例患者。移植前可能或确诊的IA发病率为6.0%（n = 87）。有和没有移植前IA的患者1年NRM的累积发生率分别为17.3%（95%CI 10.2 - 26.0）和11.2%（9.6 - 13.0）。在多变量分析中，移植前IA患者1年NRM的风险比（HR）为2.1（1.2 - 3.6；p = 0.009）。移植前IA患者的1年无病生存率较低（59.4% [48.3 - 68.9] 对 70.4 [67.9 - 72.8]；多变量HR 1.5 [1.1 - 2.1]；p = 0.02）。因此，移植前IA患者的1年总生存率较低：（68.8% [57.8 - 77.4] 对 79.0% [76.7 - 81.1]；多变量HR 1.7 [1.1 - 2.5]；p = 0.01）。
移植前IA仍然与alloSCT结局受损显著相关。另一方面，超过三分之二的移植前IA患者在alloSCT后1年时仍存活。IA不再是alloSCT的绝对禁忌证，因为大多数接受alloSCT的IA患者从该程序中获益。
本研究没有外部资金来源。
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