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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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2.
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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3.
European guidelines for primary antifungal prophylaxis in adult haematology patients: summary of the updated recommendations from the European Conference on Infections in Leukaemia
Maertens, J. A., Girmenia, C., Bruggemann, R. J., Duarte, R. F., Kibbler, C. C., Ljungman, P., Racil, Z., Ribaud, P., Slavin, M. A., Cornely, O. A., et al
The Journal of antimicrobial chemotherapy. 2018
Abstract
The European Conference on Infections in Leukaemia (ECIL) updated its guidelines on antifungal prophylaxis for adults using the grading system of IDSA. The guidelines were extended to provide recommendations for other haematological diseases besides AML and recipients of an allogeneic haematopoietic stem cell transplantation (HSCT). Posaconazole remains the drug of choice when the incidence of invasive mould diseases exceeds 8%. For patients undergoing remission-induction chemotherapy for AML and myelodysplastic syndrome (MDS), fluconazole can still offer an alternative provided it forms part of an integrated care strategy that includes screening with biomarkers and imaging. Similarly, aerosolized liposomal amphotericin B combined with fluconazole can be considered for patients at high risk of invasive mould diseases but other formulations of the polyene are discouraged. Fluconazole is still recommended as primary prophylaxis for patients at low risk of invasive mould diseases during the pre-engraftment phase of allogeneic HSCT whereas only a moderate recommendation could be made for itraconazole, posaconazole and voriconazole for patients at high risk. Posaconazole is strongly recommended for preventing invasive mould disease post-engraftment but only when graft-versus-host disease (GvHD) was accompanied by other risk factors such as its severity, use of an alternative donor or when unresponsive to standard corticosteroid therapy. The need for primary prophylaxis for other patient groups was less clear and should be defined by the estimated risk of invasive fungal disease (IFD).
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4.
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.
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5.
Influence of pre-existing invasive aspergillosis on allo-HSCT outcome: a retrospective EBMT analysis by the Infectious Diseases and Acute Leukemia Working Parties
Penack, O., Tridello, G., Hoek, J., Socie, G., Blaise, D., Passweg, J., Chevallier, P., Craddock, C., Milpied, N., Veelken, H., et al
Bone Marrow Transplantation. 2016;51(3):418-23
Abstract
Historically, invasive aspergillosis (IA) has been a major barrier for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The influence of invasive IA on long-term survival and on transplant-related complications has not been investigated in a larger patient cohort under current conditions. Our aim was to analyze the long-term outcome of patients undergoing allo-HSCT with a history of prior IA. We used European Society for Blood and Marrow Transplantation database data of first allo-HSCTs performed between 2005 and 2010 in patients with acute leukemia. One thousand one hundred and fifty patients with data on IA before allo-HSCT were included in the analysis. The median follow-up time was 52.1 months. We found no significant impact of IA on major transplant outcome variables such as overall survival, relapse-free survival, non-relapse mortality, cumulative incidence of acute GvHD grade II-IV, chronic GvHD, pulmonary complications and leukemia relapse. However, we found a trend toward lower overall survival (P=0.078, hazard ratio (HR) (95% confidence interval (CI)): 1.16 (0.98, 1.36)) and higher non-relapse mortality (P=0.150, HR (95% CI): 1.19 (0.94, 1.50)) in allo-HSCT recipients with pre-existing IA. Our data suggest that a history of IA should not generally be a contraindication when considering the performance of allo-HSCT in patients with acute leukemia.
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6.
Risk Factors for Invasive Mold Infections and Implications for Choice of Prophylaxis after Allogeneic Stem Cell Transplantation
Blennow, O., Remberger, M., Torlen, J., Szakos, A., Ljungman, P., Mattsson, J.
Biology of Blood & Marrow Transplantation. 2016;22(9):1684-9
Abstract
Invasive mold infections (IMIs) are major complications after allogeneic hematopoietic stem cell transplantation (HSCT) with high mortality. We retrospectively investigated incidence and risk factors for IMI after 797 HSCTs in a center with high autopsy frequency, trying to identify patient groups that would potentially benefit from mold-active prophylaxis. The cumulative 1-year incidence of IMI was 2.1% in patients aged 21 to 40, 7.1% in patients aged 41 to 60, and 16.4% in patients > 60 years of age (P<.01 for patients aged 21 to 40 versus 41 to 60, P<.001 for patients aged 21 to 40 versus patients > 60). Risk factors for a new IMI in multivariate analysis were older age, grades II to IV acute graft-versus-host disease (GVHD) (risk hazard, 4.1; 95% CI, 1.9 to 8.8; P<.001), treatment with mesenchymal stromal cells (risk hazard, 4.0; 95% CI, 2.1 to 7.8; P < .001), transplantation with female donor to male recipient (risk hazard, 2.2; 95% CI, 1.1 to 4.3; P = .02), and hematopoietic stem cell transplantation-specific comorbidity index over 5 (risk hazard, 2.8; 95% CI, 1.1 to 6.8; P = .03). In patients with grade II acute GVHD, no IMI was seen after onset of acute GVHD in 109 HSCTs performed in patients < 40 years of age, as compared with 14 IMIs in 97 HSCTs (14%) performed in patients > 40 years of age (P<.001). To conclude, older age is an important risk factor for developing IMIs, and patients < 40 years of age with grade II acute GVHD do not appear to need mold-active prophylaxis unless receiving prolonged treatment with corticosteroids. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.