Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working Party

Olaf Penack; Gloria Tridello; Urpu Salmenniemi; Rodrigo Martino; Nina Khanna; Katia Perruccio; Franca Fagioli; Monika Richert-Przygonska; Hélène Labussière-Wallet; Johan Maertens; Charlotte Jubert; Mahmoud Aljurf; Herbert Pichler; Gergely Kriván; Desiree Kunadt; Marina Popova; Melissa Gabriel; Elisabetta Calore; Igor Wolfgang Blau; Fabio Benedetti; Maija Itäla-Remes; Elizabeth de Kort; Domenico Russo; Maura Faraci; Anne Lise Ménard; Peter von dem Borne; Xavier Poiré; Akif Yesilipek; Jolanta Gozdzik; Zeynep Arzu Yegin; Lucrecia Yañez; Luca Facchini; Gwendolyn Van Gorkom; Lorenz Thurner; Ulker Kocak; Antònia Sampol; Tsila Zuckerman; Marc Bierings; Stephan Mielke; Fabio Ciceri; Lotus Wendel; Nina Knelange; Malgorzata Mikulska; Dina Averbuch; Jan Styczynski; Rafael de la Camara; Simone Cesaro

doi:10.1016/j.eclinm.2023.102393

Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working Party

Olaf Penack^*, Gloria Tridello, Urpu Salmenniemi, Rodrigo Martino, Nina Khanna, Katia Perruccio, Franca Fagioli, Monika Richert-Przygonska, Hélène Labussière-Wallet, Johan Maertens, Charlotte Jubert, Mahmoud Aljurf, Herbert Pichler, Gergely Kriván, Desiree Kunadt, Marina Popova, Melissa Gabriel, Elisabetta Calore, Igor Wolfgang Blau, Fabio BenedettiMaija Itäla-Remes, Elizabeth de Kort, Domenico Russo, Maura Faraci, Anne Lise Ménard, Peter von dem Borne, Xavier Poiré, Akif Yesilipek, Jolanta Gozdzik, Zeynep Arzu Yegin, Lucrecia Yañez, Luca Facchini, Gwendolyn Van Gorkom, Lorenz Thurner, Ulker Kocak, Antònia Sampol, Tsila Zuckerman, Marc Bierings, Stephan Mielke, Fabio Ciceri, Lotus Wendel, Nina Knelange, Malgorzata Mikulska, Dina Averbuch, Jan Styczynski, Rafael de la Camara, Simone Cesaro

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	102393
Number of pages	10
Journal	EClinicalMedicine
Volume	67
DOIs	https://doi.org/10.1016/j.eclinm.2023.102393
Publication status	Published - 1 Jan 2024

Keywords

Aspergillosis
Invasive
Mortality
Stem cell transplantation

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10.1016/j.eclinm.2023.102393Licence: CC BY-NC-ND

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Penack, O., Tridello, G., Salmenniemi, U., Martino, R., Khanna, N., Perruccio, K., Fagioli, F., Richert-Przygonska, M., Labussière-Wallet, H., Maertens, J., Jubert, C., Aljurf, M., Pichler, H., Kriván, G., Kunadt, D., Popova, M., Gabriel, M., Calore, E., Blau, I. W., ... Cesaro, S. (2024). Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working Party. EClinicalMedicine, 67, Article 102393. https://doi.org/10.1016/j.eclinm.2023.102393

@article{080d09c345de482d8d4c3ceb366901d7,

title = "Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working Party",

abstract = "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.",

keywords = "Aspergillosis, Invasive, Mortality, Stem cell transplantation",

author = "Olaf Penack and Gloria Tridello and Urpu Salmenniemi and Rodrigo Martino and Nina Khanna and Katia Perruccio and Franca Fagioli and Monika Richert-Przygonska and H{\'e}l{\`e}ne Labussi{\`e}re-Wallet and Johan Maertens and Charlotte Jubert and Mahmoud Aljurf and Herbert Pichler and Gergely Kriv{\'a}n and Desiree Kunadt and Marina Popova and Melissa Gabriel and Elisabetta Calore and Blau, {Igor Wolfgang} and Fabio Benedetti and Maija It{\"a}la-Remes and {de Kort}, Elizabeth and Domenico Russo and Maura Faraci and M{\'e}nard, {Anne Lise} and Borne, {Peter von dem} and Xavier Poir{\'e} and Akif Yesilipek and Jolanta Gozdzik and Yegin, {Zeynep Arzu} and Lucrecia Ya{\~n}ez and Luca Facchini and {Van Gorkom}, Gwendolyn and Lorenz Thurner and Ulker Kocak and Ant{\`o}nia Sampol and Tsila Zuckerman and Marc Bierings and Stephan Mielke and Fabio Ciceri and Lotus Wendel and Nina Knelange and Malgorzata Mikulska and Dina Averbuch and Jan Styczynski and Camara, {Rafael de la} and Simone Cesaro",

note = "Funding Information: OP acknowledges the support of Jos{\'e} Carreras Leuk{\"a}mie-Stiftung (3R/2019, 23R/2021), Deutsche Krebshilfe (70113519), Deutsche Forschungsgemeinschaft (PE 1450/7-1, PE 1450/9-1) and Stiftung Charit{\'e} BIH (BIH_PRO_549, Focus Group Vascular Biomedicine). Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2024",

month = jan,

day = "1",

doi = "10.1016/j.eclinm.2023.102393",

language = "English",

volume = "67",

journal = "EClinicalMedicine",

issn = "2589-5370",

publisher = "Elsevier",

}

Penack, O, Tridello, G, Salmenniemi, U, Martino, R, Khanna, N, Perruccio, K, Fagioli, F, Richert-Przygonska, M, Labussière-Wallet, H, Maertens, J, Jubert, C, Aljurf, M, Pichler, H, Kriván, G, Kunadt, D, Popova, M, Gabriel, M, Calore, E, Blau, IW, Benedetti, F, Itäla-Remes, M, de Kort, E, Russo, D, Faraci, M, Ménard, AL, Borne, PVD, Poiré, X, Yesilipek, A, Gozdzik, J, Yegin, ZA, Yañez, L, Facchini, L, Van Gorkom, G, Thurner, L, Kocak, U, Sampol, A, Zuckerman, T, Bierings, M, Mielke, S, Ciceri, F, Wendel, L, Knelange, N, Mikulska, M, Averbuch, D, Styczynski, J, Camara, RDL & Cesaro, S 2024, 'Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working Party', EClinicalMedicine, vol. 67, 102393. https://doi.org/10.1016/j.eclinm.2023.102393

Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working Party. / Penack, Olaf; Tridello, Gloria; Salmenniemi, Urpu et al.
In: EClinicalMedicine, Vol. 67, 102393, 01.01.2024.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation

T2 - a prospective study of the EBMT Infectious Diseases Working Party

AU - Penack, Olaf

AU - Tridello, Gloria

AU - Salmenniemi, Urpu

AU - Martino, Rodrigo

AU - Khanna, Nina

AU - Perruccio, Katia

AU - Fagioli, Franca

AU - Richert-Przygonska, Monika

AU - Labussière-Wallet, Hélène

AU - Maertens, Johan

AU - Jubert, Charlotte

AU - Aljurf, Mahmoud

AU - Pichler, Herbert

AU - Kriván, Gergely

AU - Kunadt, Desiree

AU - Popova, Marina

AU - Gabriel, Melissa

AU - Calore, Elisabetta

AU - Blau, Igor Wolfgang

AU - Benedetti, Fabio

AU - Itäla-Remes, Maija

AU - de Kort, Elizabeth

AU - Russo, Domenico

AU - Faraci, Maura

AU - Ménard, Anne Lise

AU - Borne, Peter von dem

AU - Poiré, Xavier

AU - Yesilipek, Akif

AU - Gozdzik, Jolanta

AU - Yegin, Zeynep Arzu

AU - Yañez, Lucrecia

AU - Facchini, Luca

AU - Van Gorkom, Gwendolyn

AU - Thurner, Lorenz

AU - Kocak, Ulker

AU - Sampol, Antònia

AU - Zuckerman, Tsila

AU - Bierings, Marc

AU - Mielke, Stephan

AU - Ciceri, Fabio

AU - Wendel, Lotus

AU - Knelange, Nina

AU - Mikulska, Malgorzata

AU - Averbuch, Dina

AU - Styczynski, Jan

AU - Camara, Rafael de la

AU - Cesaro, Simone

N1 - Funding Information: OP acknowledges the support of José Carreras Leukämie-Stiftung (3R/2019, 23R/2021), Deutsche Krebshilfe (70113519), Deutsche Forschungsgemeinschaft (PE 1450/7-1, PE 1450/9-1) and Stiftung Charité BIH (BIH_PRO_549, Focus Group Vascular Biomedicine). Publisher Copyright: © 2023 The Authors

PY - 2024/1/1

Y1 - 2024/1/1

N2 - 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.

AB - 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.

KW - Aspergillosis

KW - Invasive

KW - Mortality

KW - Stem cell transplantation

U2 - 10.1016/j.eclinm.2023.102393

DO - 10.1016/j.eclinm.2023.102393

M3 - Article

SN - 2589-5370

VL - 67

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 102393

ER -