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1.
Epidemiology, outcomes and risk factors for recurrence of Clostridioides difficile infections following allogeneic hematopoietic cell transplantation: a longitudinal retrospective multicenter study
Ragozzino, S., Mueller, N. J., Neofytos, D., Passweg, J., Müller, A., Medinger, M., Van Delden, C., Masouridi-Levrat, S., Chalandon, Y., Tschudin-Sutter, S., et al
Bone marrow transplantation. 2023
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Monitoring for virus-specific T-cell responses and viremia in allogeneic HSCT recipients: a survey from the EBMT Cellular Therapy & Immunobiology Working Party
Greco, R., Hoogenboom, J. D., Bonneville, E. F., Anagnostopoulos, A., Cuoghi, A., Dalle, J. H., Weissinger, E. M., Lang, P., Galaverna, F., Martino, M., et al
Bone marrow transplantation. 2023;:1-4
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HEV infection in stem cell transplant recipients-retrospective study of EBMT Infectious Diseases Working Party
Mikulska, M., Penack, O., Wendel, L., Knelange, N., Cornelissen, J. J., Blijlevens, N., Passweg, J., Kroger, N., Bruns, A., Koenecke, C., et al
Bone marrow transplantation. 2021
Abstract
HEV infection is an emerging cause of acute and chronic hepatitis in stem cell transplant (SCT) recipients. We performed a retrospective observational study among EBMT centers with the aim of describing characteristics, management and outcome of HEV after SCT. There were 34 cases of HEV infection from 12 centers in 6 countries, diagnosed in median 4.5 months after SCT; 20 of acute and 14 of chronic infection. Non-hepatic findings possibly associated with HEV infection were present in 9 (26%). Patients with chronic infection had more characteristics associated with severely immunocompromised status. Ribavirin was provided to 16 patients (47%; 40% with acute and 57% with chronic infection), in median for 75 days. Three (19%) patients discontinued it due to side effects. HEV-RNA clearance occurred in 29 patients (85%; 85% in acute and 86% in chronic infection). HEV was considered a cause of death in 3 (9%), with 2 cases with late diagnosis. Reduction of immunosuppression in those receiving it, and ribavirin treatment in those with chronic infection were associated with shorter time to HEV-RNA clearance. Policy on HEV testing varied between the centers. In conclusion, acute and chronic HEV hepatitis should be promptly diagnosed and managed in SCT recipients.
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4.
Legionellosis after hematopoietic stem cell transplantation
Mikulska, M., Tridello, G., Hoek, J., Gil, L., Yañez, L., Labussière-Wallet, H., Passweg, J., Xhaard, A., Pioltelli, P., Caillot, D., et al
Bone marrow transplantation. 2021
Abstract
Limited data are available on legionellosis after hematopoietic stem cell transplant (HSCT). The aim of this study was to report the cases of legionellosis and to identify predictors of legionellosis, legionellosis-associated death, and non-relapse mortality (NRM). All cases of post-HSCT legionellosis from the EBMT registry were included and matched with controls in a 3:1 ratio for the analyses of risk factors. In the years 1995-2016, 80 cases from 52 centers in 14 countries were identified (mainly from France, Italy, and Spain). Median time from HSCT to legionellosis was 203 days (range, 0-4099); 19 (23.8%) patients developed early legionellosis (within-day +30 post-HSCT). Patients were mainly male (70%), after allogeneic HSCT (70%), with acute leukemia (27.5%), lymphoma (23.8%), or multiple myeloma (21.3%), and the median age of 46.6 (range, 7.2-68.2). Predictors of legionellosis were allogeneic HSCT (OR?=?2.27, 95%CI:1.08-4.80, p?=?0.03) and recent other infection (OR?=?2.96, 95%CI:1.34-6.52, p?=?0.007). Twenty-seven (33.8%) patients died due to legionellosis (44% after early legionellosis), NRM was 50%. Predictors of NRM were female sex (HR?=?2.19, 95%CI:1.13-4.23, p?=?0.02), early legionellosis (HR?=?2.24, 95%CI:1.13-4.46, p?=?0.02), and south-eastern geographical region (HR?=?2.16, 95%CI:1.05-4.44, p?=?0.036). In conclusion, legionellosis is a rare complication after HSCT, mainly allogeneic, occurring frequently within 30 days after HSCT and associated with high mortality.
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5.
Incidence and impact of Epstein-Barr virus events in the early phase after allogeneic hematopoietic cell transplantation
Macy, S., Passweg, J., Medinger, M.
Annals of hematology. 2021
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6.
Incidence of CMV Replication and the Role of Letermovir Primary/Secondary Prophylaxis in the Early Phase After Allogeneic Hematopoietic Stem Cell Transplantation - A Single Centre Study
Studer, U., Khanna, N., Leuzinger, K., Hirsch, H. H., Heim, D., Lengerke, C., Tsakiris, D. A., Halter, J., Gerull, S., Passweg, J., et al
Anticancer research. 2020;40(10):5909-5917
Abstract
BACKGROUND/AIM: Cytomegalovirus (CMV) replication may cause life-threatening complications after allogeneic haematopoietic stem cell transplantation (allo-HSCT). The aim of the study was to characterize CMV events, and the outcome of letermovir (LTV) CMV prophylaxis. PATIENTS AND METHODS In this retrospective analysis of patients treated with an allo-HSCT between 2010 and 2020, we determined plasma CMV events, as well as associated risk factors. RESULTS We identified 423 patients who had undergone allo-HSCT between 2010 and 2020. CMV DNAemia was found in 130/423 (30.7%) of patients. CMV reactivation rate was significantly higher in patients with acute graft-versus-host disease, HLA mismatch, and CMV IgG seropositivity of donors and recipients. Among 42 patients receiving LTV prophylaxis those, 5 (11.9%) showed CMV DNAemia under LTV versus 87/353 (24.6%) in a control group. CONCLUSION Despite the development of better approaches with weekly monitoring and early treatment initiation, CMV reactivations play an important role after allo-HSCT.
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Microbiologically documented infections after adult allogeneic hematopoietic cell transplantation: a 5-year analysis within the Swiss Transplant Cohort study
Vu, D. L., Dayer, J. A., Masouridi-Levrat, S., Combescure, C., Boely, E., Khanna, N., Mueller, N. J., Kleber, M., Medinger, M., Halter, J., et al
Transplant infectious disease : an official journal of the Transplantation Society. 2020;:e13289
Abstract
BACKGROUND Infections are an important complication after allogeneic hematopoietic cell transplantation (allo-HCT). The present study aimed at determining the landscape of infections occurring in a large cohort of allo-HCT patients, as well as associated risk factors for infections and for one-year non-relapse mortality. METHODS This is a retrospective cohort study using STCS and EBMT databases to assess the one-year incidence rate of infection, as well as risk factors for infections and for one-year non-relapse mortality among adult allo-HCT patients transplanted between 2010 and 2014 in Switzerland. Univariable and multivariable quasi Poisson and multivariable Cox regression models were used. RESULTS Of 553 patients included, 486 had an infection with a global incidence rate of 3.66 infections per patient-year. Among a total of 1534 infections analyzed, viral infections were predominant (n=1138, 74.2%), followed by bacterial (n=343, 22.4%) and fungal (n=53, 3.5%) infections. At one year, the cumulative incidence of relapse and non-relapse mortality were 26% and 16%, respectively. 195 (35.3%) of patients had at least one episode of severe graft-versus-host-disease (GvHD). A center effect was observed, and underlying disease, donor type, cytomegalovirus serological constellation and GvHD were also associated with the incidence rate of infections. There was an increased risk for one-year non-relapse mortality associated with all pathogens, specifically within two months of infection, and this remained true beyond 2 months of a fungal infection. CONCLUSION Despite advances to limit infections in this population, they still occur in most allo-HCT patients with a major impact on survival at one year.
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Clinical considerations on posaconazole administration and therapeutic drug monitoring in allogeneic hematopoietic cell transplant recipients
Kraljevic, M., Khanna, N., Medinger, M., Passweg, J., Masouridi-Levrat, S., Chalandon, Y., Mueller, N. J., Schanz, U., Vernaz, N., Van Delden, C., et al
Medical mycology. 2020
Abstract
There is a paucity of data on posaconazole (PCZ) dosing and therapeutic-drug-monitoring (TDM) in allogeneic hematopoietic cell transplant recipients (allogeneic-HCTr). This was a 3-year retrospective multicenter study (January 1, 2016 to December 31, 2018) in adult allogeneic-HCTr who received PCZ (intravenously, IV and/or as delayed-release tablet, DRT) as prophylaxis or treatment for =7 consecutive days (D) with at least 1-PCZ-level available using data of the Swiss Transplant Cohort Study. The primary objective was to describe the distribution of PCZ-level and identify predictors of therapeutic PCZ-level and associations between PCZ-dosing and PCZ-level. A total of 288 patients were included: 194 (67.4%) and 94 (32.6%) received PCZ as prophylaxis and treatment, respectively, for a median of 90 days (interquartile range, IQR: 42-188.5). There were 1944 PCZ-level measurements performed, with a median PCZ level of 1.3 mg/L (IQR: 0.8-1.96). PCZ-level was <0.7 mg/L in 383/1944 (19.7%) and <1.0 mg/L in 656/1944 (33.7%) samples. PCZ-level was <0.7 mg/L in 260/1317 (19.7%) and <1.0 mg/L in 197/627 (31.4%) in patients who received PCZ-prophylaxis versus treatment, respectively. There were no significant differences in liver function tests between baseline and end-of-treatment. There were nine (3.1%) breakthrough invasive fungal infections (bIFI), with no difference in PCZ levels between patients with or without bIFI. Despite a very intensive PCZ-TDM, PCZ-levels remain below target levels in up to one-third of allogeneic-HCTr. Considering the low incidence of bIFI observed among patients with PCZ levels in the targeted range, our data challenge the clinical utility of routine universal PCZ-TDM.
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Seasonal human coronaviruses respiratory tract infection in recipients of allogeneic hematopoietic stem cell transplantation
Piñana, J. L., Xhaard, A., Tridello, G., Passweg, J., Kozijn, A., Polverelli, N., Heras, I., Perez, A., Sanz, J., Berghuis, D., et al
The Journal of infectious diseases. 2020
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Abstract
BACKGROUND Little is known about characteristics of seasonal human coronavirus (HCoV) (NL63, 229E, OC43 and HKU1) after allogeneic stem cell transplantation (allo-HCT). PATIENTS AND METHODS this is a collaborative Spanish and European bone marrow transplantation groups retrospective multicentre study, which included allo-HCT recipients (adults and children) with upper and/or lower respiratory tract disease (U/LRTD) caused by seasonal HCoV diagnosed through multiplex PCR assays from January 2012 to January 2019. RESULTS We included 402 allo-HCT recipients who developed 449 HCoV U/LRTD episodes. Median age of recipients was 46 years (range 0.3-73.8 years). HCoV episodes were diagnosed at a median of 222 days after transplantation. The most common HCoV subtype was OC43 (n=170, 38%). LRTD involvement occurred in 121 episodes (27%). HCoV infection frequently required hospitalization (18%), oxygen administration (13%) and intensive care unit (ICU) admission (3%). Three-month overall mortality after HCoV detection was 7% in the whole cohort and 16% in those with LRTD. We identified 3 conditions associated with higher mortality in recipients with LRTD absolute lymphocyte count <0.1 x10 9/mL [hazard ratio (HR), 10.8], corticosteroid (HR 4.68) and ICU admission (HR 8.22) (p<0.01). CONCLUSIONS Seasonal HCoV after allo-HCT may involve the LRTD in many instances, leading to a significant morbidity.
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10.
Optimal Treatment Duration of Pseudomonas aeruginosa Infections in Allogeneic Hematopoietic Cell Transplant Recipients
Olearo, F., Kronig, I., Masouridi-Levrat, S., Chalandon, Y., Khanna, N., Passweg, J., Medinger, M., Mueller, N. J., Schanz, U., Van Delden, C., et al
Open forum infectious diseases. 2020;7(7):ofaa246
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Abstract
In a large, multicenter, contemporary, 8-year, cohort study, one third of allogeneic-hematopoietic cell transplant (HCT) recipients with Pseudomonas aeruginosa (PSA) infection developed a recurrent infection within 3 months. Antibiotic treatment duration of ≥14 days was the only significantly associated variable with reduced recurrence rates of PSA infections in allogeneic-HCT recipients.