Background: 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.
Methods: 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.
Findings: 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).
Interpretation: 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.
Funding: There was no external funding source for this study.
Competing Interests: R.dlC. Has received honoraria from Pfizer and MSD; J.S. reports personal fees from Gilead, outside the submitted work. EDK reports grants from Gilead sciences, personal fees from Pfizer, outside the submitted work. L.Y. reports grants and personal fees from Janssen, personal fees from Abbvie, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Beigene, personal fees and non-financial support from Kite/Gilead, personal fees and non-financial support from Pfizer, outside the submitted work; S.M reports other from Celgene/BMS, other from Novartis, other from Kite/Gilead, other from Pfizer, other from Miltenyi, other from Mendes, other from SWECARNET, other from Scientify Research, outside the submitted work; J.M. reports personal fees and non-financial support from Gilead Sciences, personal fees and non-financial support from Mundipharma, personal fees and non-financial support from F2G, personal fees and non-financial support from Takeda, personal fees and non-financial support from Basilea, outside the submitted work; M.M. reports grants and personal fees from Gilead, personal fees from Mundipharma, personal fees from Pfizer, from null, outside the submitted work; H.P. reports non-financial support from Neovii, during the conduct of the study; OP has no COIs directly related to this work. HP reports non-financial support from Neovii during the conduct of the study; OP has received honoraria or travel support from Gilead, Jazz, MSD, Neovii, Novartis, Pfizer and Therakos. He has received research support from Incyte and Priothera. He is member of advisory boards to Equillium Bio, Jazz, Gilead, Novartis, MSD, Omeros, Orca Bio, Priothera, Sanofi, Shionogi and SOBI. T.Z. reports personal fees from AbbVie, personal fees from Orgenesis Inc, personal fees from BioSight Ltd, personal fees from Cellect Biotechnology, personal fees from Janssen, personal fees from Novartis, personal fees from Gilead Sciences, outside the submitted work. The remaining authors declare no conflict of interests.
(© 2023 The Authors.)