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1.
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, O., Tridello, G., Salmenniemi, U., Martino, R., Khanna, N., Perruccio, K., Fagioli, F., Richert-Przygonska, M., Labussière-Wallet, H., Maertens, J., et al
EClinicalMedicine. 2024;67:102393
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.
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2.
Pneumocystis pneumonia after allogeneic hematopoietic cell transplantation: A case-control study on epidemiology and risk factors on behalf of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation
Robin, C., Cordonnier, C., Tridello, G., Knelange, N., Xhaard, A., Chantepie, S., Tanguy-Schmidt, A., Schouten, H. C., Yesherun, M., Rocha, V., et al
Transplantation and cellular therapy. 2023
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3.
Endemic or regionally limited parasitic and fungal infections in haematopoietic stem-cell transplantation recipients: a Worldwide Network for Blood and Marrow Transplantation (WBMT) Review
Muhsen, I. N., Galeano, S., Niederwieser, D., Koh, M. B. C., Ljungman, P., Machado, C. M., Kharfan-Dabaja, M. A., de la Camara, R., Kodera, Y., Szer, J., et al
The Lancet. Haematology. 2023;10(4):e295-e305
Abstract
There is a scarcity of data on endemic and regionally limited fungal and parasitic infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America. This Worldwide Network for Blood and Marrow Transplantation (WBMT) Review is one of two papers aiming to provide guidance to transplantation centres worldwide regarding prevention, diagnosis, and treatment based on the currently available evidence and expert opinion. These recommendations were created and reviewed by physicians with expertise in HSCT or infectious disease, representing several infectious disease and HSCT groups and societies. In this paper, we review the literature on several endemic and regionally limited parasitic and fungal infections, some of which are listed as neglected tropical diseases by WHO, including visceral leishmaniasis, Chagas disease, strongyloidiasis, malaria, schistosomiasis, histoplasmosis, blastomycosis, and coccidioidomycosis.
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4.
8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation
Groll, A. H., Pana, D., Lanternier, F., Mesini, A., Ammann, R. A., Averbuch, D., Castagnola, E., Cesaro, S., Engelhard, D., Garcia-Vidal, C., et al
The Lancet. Oncology. 2021;22(6):e254-e269
Abstract
Paediatric patients with cancer and those undergoing allogeneic haematopoietic cell transplantation have an increased susceptibility to invasive fungal diseases. In addition to differences in underlying conditions and comorbidities relative to adults, invasive fungal diseases in infants, children, and adolescents are unique in terms of their epidemiology, the validity of current diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of phase 3 clinical trials to provide data to guide evidence-based interventions. To re-examine the state of knowledge and to further improve invasive fungal disease diagnosis, prevention, and management, the 8th European Conference on Infections in Leukaemia (ECIL-8) reconvened a Paediatric Group to review the literature and to formulate updated recommendations according to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) grading system, which are summarised in this Review.
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5.
Impact of early candidemia on the long-term outcome of allogeneic hematopoietic stem cell transplant in non-leukemic patients: an outcome analysis on behalf of IDWP-EBMT
Cesaro, S., Tridello, G., Knelange, N. S., Blijlevens, N., Martin, M., Snowden, J. A., Malladi, R., Ljungman, P., Deconinck, E., Gedde-Dahl, T., et al
Bone marrow transplantation. 2021
Abstract
We assessed the incidence and outcome of early candidemia after hematopoietic stem cell transplant (HSCT). The analysis included all first HSCTs performed from 2000 to 2015 in adult and pediatric patients with a non-leukemic disease and recorded in the EBMT registry. Overall survival (OS), non-relapse mortality (NRM), and relapse mortality (RM) were evaluated. Candidemia was diagnosed in 420 of 49,852 patients at a median time of 17 days post HSCT (range 0-100), the cumulative incidence being 0.85%. In 65.5% of episodes, candidemia occurred by day 30 after HSCT. The mortality rate by day 7 was 6.2%, whereas 100-day NRM was higher (HR 3.47, p?0.0001), and 100-day OS was lower (HR 3.22, p?0.0001) than that of patients without candidemia. After a median follow-up of 4.3 years, 5-year OS, NRM, and RM for patients with and without candidemia were 50.5% vs. 60.8%, p?0.0001, 28.2% vs.18.8%, p?0.0001, and 25.3% vs. 27.2%, p?=?0.4, respectively. In conclusion, in non-leukemic transplant patients, the occurrence of an early episode of candidemia is rare but it is still associated with a negative effect on the outcome.
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6.
Epidemiology and outcome of invasive fungal disease in children after hematopoietic cell transplantation or treated for malignancy: impact of national program of antifungal prophylaxis
Czyzewski, K., Galazka, P., Fraczkiewicz, J., Salamonowicz, M., Szmydki-Baran, A., Zajac-Spychala, O., Gryniewicz-Kwiatkowska, O., Zalas-Wiecek, P., Chelmecka-Wiktorczyk, L., Irga-Jaworska, N., et al
Mycoses. 2019
Abstract
BACKGROUND The objective of the study was the analysis of incidence and outcome of invasive fungal disease (IFD) in children treated for malignancy (PHO, pediatric hematology-oncology) or undergoing hematopoietic cell transplantation (HCT) over a period of 6 consecutive years in nationwide study. PATIENTS AND METHODS Total number of 5628 patients with newly-diagnosed malignancies and 971 patients after HCT (741 allo-HCT and 230 auto-HCT) were screened for infectious complications in biennial reports. RESULTS IFD incidence was lower among PHO patients: 8.8% vs 21.2% (p<0.0001), and survival from IFD was better: 94.2% vs 84.1% (p<0.0001). Auto-HCT patients had lower incidence (10.9% vs 24.4%) and lower mortality than allo-HCT patients. Introduction of national antifungal prophylaxis program in HCT and acute leukemia patients decreased incidence of IFD in HCT (from 23.1% to 13.4%) and AML on conventional chemotherapy (from 36% to 23%) but not in ALL patients during chemotherapy. In multivariate analysis, the incidence of IFD was higher in patients after HCT, diagnosed for ALL, AML or NHL, and in patients >10 years old. Factors contributing to death with infection were: undergoing HCT, diagnosis of acute leukemia (ALL or AML) and duration of treatment of infection >21 days. CONCLUSIONS The incidence of IFD in allo-HCT and in AML patients on chemotherapy has decreased after introduction of national program of antifungal prophylaxis, while the incidence of IFD in ALL patients on chemotherapy did not change significantly. The outcome of IFD both in PHO and HCT patients has largely improved in comparison to historical international data. This article is protected by copyright. All rights reserved.
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7.
Incidence, Risk Factors and Long-Term Outcome of Acute Leukemia Patients with Early Candidemia after Allogeneic Stem Cell Transplantation. A Study by the Acute Leukemia and Infectious Diseases Working Parties of EBMT
Cesaro, S., Tridello, G., Blijlevens, N., Ljungman, P., Craddock, C., Michallet, M., Martin, A., Snowden, J. A., Mohty, M., Maertens, J., et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018
Abstract
Objectives: To assess the incidence of, and risk factors for, Candida infection in the first 100 days after allogeneic hematopoietic stem cell transplantation (HSCT) and the impact on long-term survival. Methods: outcome analysis of 28,542 acute leukemia patients who underwent HSCT from 2000 to 2012: 347 with candidemia by day +100, and 28,195 without candidemia or any other type of Candida infection. Results: The incidence of candidemia by day +100 was 1.2% (347/28542) and occurred at a median of 22 days after HSCT (range 1-100). A higher 100-day non-relapse-mortality (NRM) (HR 3.0, p <0.0001), and a lower 100-day overall-survival (OS) (HR 2.5, p<0.0001) were observed in patients with candidemia. The case fatality rate by day +100 in patients with candidemia was 22% (76/347). Factors associated with candidemia occurrence were: gender female, bone marrow or cord blood stem cell source, T-cell depletion, use of total body irradiation, and acute graft versus host disease. Among the patients alive at day +100, the 5-year NRM and OS after a median follow-up of 5.6 years (95% CI 5.5 - 5.7) for patients with and without candidemia were 22.5% vs. 13.5%, p <0.0001, and 45.6% vs. 53.4%, p=0.0003, respectively. In multivariate analysis, the occurrence of a candidemia episode by day +100 was an independent risk factor for higher NRM, HR 1.7, p=0.001, and lower OS, HR 1.4, p=0.001. Conclusions: despite the general improvements in prophylaxis and treatment, the early occurrence of candidemia after HSCT is still associated with higher NRM and lower short-and-long-term OS.