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1.
At-Home Foscarnet Administration in Patients with Cytomegalovirus Infection Post-Allogeneic Stem Cell Transplantation: A Unicentric, Safe, and Feasible Program
Ruiz-Boy, S., Pedraza, A., Prat, M., Salas, M. Q., Carcelero, E., Riu-Viladoms, G., Suárez-Lledó, M., Monge-Escartín, I., Rodríguez-Lobato, L. G., Martínez-Roca, A., et al
Pharmaceuticals (Basel, Switzerland). 2023;16(12)
Abstract
Cytomegalovirus (CMV) infection is a relevant cause of morbimortality in patients receiving allogeneic stem cell transplantation (allo-HCT). Foscarnet (FCN) is an effective drug against CMV administered intravenously and usually on an inpatient basis. The Home Care Unit (HCU) for hematologic patients at our hospital designed an at-home FCN administration model to avoid the hospitalization of patients requiring FCN treatment. This study analyzes whether the at-home administration of FCN is as safe and effective as its hospital administration. We collected and compared demographic, clinical, analytical, and economic data of patients with CMV infection post-allo-HCT who received FCN in the hospital (n = 16, 17 episodes) vs. at-home (n = 67, 88 episodes). The proportions of patients with cured CMV infections were comparable between the two groups (65.9% vs. 76.5%, p = 0.395). The median duration of FCN treatment was 15 (interquartile range [IQR] 9-23) and 14 (IQR 11-19) days in the HCU and inpatient cohorts, respectively (p = 0.692). There were no significant differences in the FCN toxicities between groups except for hypocalcemia (26.1% vs. 58.8%, p = 0.007), which was more prevalent in the inpatient cohort. A significant cost-effectiveness was found in the HCU cohort, with a median savings per episode of EUR 5270. It may be concluded that home administration of FCN is a safe, effective, and cost-efficient therapeutic option for patients with CMV infection and disease.
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2.
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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3.
Impact of letermovir prophylaxis in CMV reactivation and disease after allogenic hematopoietic cell transplantation: a real-world, observational study
Brusosa, M., Ruiz, S., Monge, I., Solano, M. T., Rosiñol, L., Esteve, J., Carreras, E., Marcos, MÁ, Riu, G., Carcelero, E., et al
Annals of hematology. 2023
Abstract
Letermovir for CMV prevention in CMV-seropositive adults undergoing allo-HCT was implemented at our program in 2021. This study investigates the results from the use of letermovir. The study includes all the 140 CMV-seropositive patients who underwent an allo-HCT during the years 2020, 2021, and 2022 at our institution. Thirty-eight (27.4%) of these patients received letermovir, administered from day + 7 to day + 100 and restarted if patients were on treatment with steroids. The day + 180 and 1-year cumulative incidences of CMV reactivation were 5.3% and 12.1% for patients who received letermovir and 52.9% and 53.9% for those who did not (P < 0.001) (HR 0.19, P < 0.001). Four (10.5%) of these thirty-eight patients had a CMV reactivation, but only 2 (5.3%) cases occurred during the administration of letermovir. During the first year after allo-HCT, 13 (9.2%) patients had CMV disease; the day + 180 and 1-year cumulative incidences were 2.6% and 6.0% for patients who received letermovir and 9.9% and 12.3% for those who did not (P = 0.254) (HR 1.01, P = 0.458). Two (4.2%) of the patients included in the letermovir group had CMV disease, but both of them after letermovir discontinuation. Letermovir induced a protective effect on CMV reactivation risk, but its use was not associated with a significant reduction of CMV disease. The fact that the CMV disease in patients who received letermovir occurred after the discontinuation of the drug, questions whether CMV prophylaxis should be used in patients with high risk for CMV reactivation or disease.
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4.
Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations
Greco, R., Alexander, T., Burman, J., Del Papa, N., de Vries-Bouwstra, J., Farge, D., Henes, J., Kazmi, M., Kirgizov, K., Muraro, P. A., et al
Bone Marrow Transplantation. 2021
Abstract
Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an "endemic" phase and therefore an ongoing risk within a "new normality". These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice.
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5.
Assessment of the association between Cytomegalovirus DNAemia and subsequent acute Graft-versus-Host Disease in allogeneic peripheral blood stem cell transplantation: A multicenter study from the Spanish Hematopoietic Transplantation and Cell Therapy Group
Bueno, F., Solano, C., Vázquez, L., Giménez, E., de la Cámara, R., Albert, E., Rovira, M., Espigado, I., Martín Calvo, C., López-Jiménez, J., et al
Transplant infectious disease : an official journal of the Transplantation Society. 2021;:e13627
Abstract
The potential role of active CMV infection in promoting acute Graft-versus-Host Disease (aGvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. We further addressed this issue conducting a retrospective, observational, multicenter study of 632 patients subjected to allogeneic peripheral blood HSCT at 20 Spanish centers. Monitoring of CMV DNA load in plasma or whole blood was performed by real-time PCR assays. Cumulative incidence of CMV DNAemia was 48.9% (95% CI, 45%-52.9%), of any grade aGvHD, 45.6; 95% (CI, 41.3%-50.1%), and of grade II-IV aGvHD, 30.7 (95% CI, 24.9%-36.4%). Overall, development of CMV DNAemia at any level resulted in an increased risk of subsequent all grade (HR, 1.38; 95% CI, 1.08 - 1.76; P=0.009) or grade II-IV (HR, 1.58; 95% CI, 1.22 - 2.06; P=0.001) aGvHD. The increased risk of aGvHD linked to prior occurrence of CMV DNAemia was similar to the above when only clinically significant episodes were considered for the analyses (HR for all grade aGvHD, 1.48; 95% CI, 1.13 - 1.91; P=0.041, and HR for grade II-IV aGvHD, 1.53; 95% CI. 1.13-1.81; P=0.04). The CMV DNA doubling time in blood was comparable overall in episodes of CMV DNAemia whether followed by aGvHD or not. Whether CMV replication is a surrogate risk marker of aGvHD or it is causally involved is an important question to be addressed in future experimental research.
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6.
Clinical outcomes of allogeneic hematopoietic stem cell transplant recipients developing Cytomegalovirus DNAemia prior to engraftment
Solano, C., Vázquez, L., Giménez, E., de la Cámara, R., Albert, E., Rovira, M., Espigado, I., Calvo, C. M., López-Jiménez, J., Suárez-Lledó, M., et al
Bone marrow transplantation. 2020
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Editor's Choice
Abstract
There is limited information on the impact of CMV DNAemia episodes developing prior to engraftment (pre-CMV DNAemia) on clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). This issue was addressed in the current retrospective multicenter study including 878 patients. All participant centers used preemptive antiviral therapy strategies for prevention of CMV disease. CMV DNA load in blood was monitored by real-time PCR assays. A total of 144 patients (cumulative incidence 16.5%, 95% CI, 14%-19%) had an episode of pre-CMV DNAemia at a median of 10 days after allo-HSCT. Patients who developed pre-CMV DNAemia had a significantly higher (P?=?0.001) probability of recurrent episodes (50%) than those who experienced post-CMV DNAemia (32.9%); Nevertheless, the incidence of CMV disease was comparable (P?=?0.52). Cumulative incidences of overall mortality (OM) and non-relapse mortality (NRM) at 1-year after allo-HSCT were 32% (95% CI, 29-35%) and 23% (95% CI 20-26%), respectively. The risk of OM and NRM in adjusted models appeared comparable in patients developing a single episode of CMV DNAemia, regardless of whether it occurred before or after engraftment, in patients with pre- and post-engraftment CMV DNAemia episodes or in those without CMV DNAemia.
PICO Summary
Population
Adult patients undergoing T-cell replete allo-HSCT (n=1116)
Intervention
Identification of patients with pre-CMV DNAemia (n=144)
Comparison
Patients with post-CMV DNAemia (n=423)
Outcome
Patients who developed pre-CMV DNAemia had a significantly higher probability of recurrent episodes (50%) than those who experienced post-CMV DNAemia (32.9%); Nevertheless, the incidence of CMV disease was comparable. Cumulative incidences of overall mortality (OM) and non-relapse mortality (NRM) at 1-year after allo-HSCT were 32% and 23%, respectively.
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7.
Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group
Solano, C., Vázquez, L., Giménez, E., de la Cámara, R., Albert, E., Rovira, M., Espigado, I., Calvo, C. M., López-Jiménez, J., Suárez-Lledó, M., et al
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2020
Abstract
The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs =500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.
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8.
Steroid's Deleterious Effect on CMV Infection Rate Post-Allo-SCT Depends on Pre-Transplant CMV Serostatus of Donors and Recipients
Suarez-Lledo, M., Martinez-Cibrian, N., Gutierrez-Garcia, G., Dimova-Svetoslavova, V., Marcos, M. A., Martin-Antonio, B., Martinez-Trillos, A., Villamor, N., Rosinol, L., Martinez, C., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
This study examined the impact of prednisone (PDN) on CMV infection after allogeneic stem cell transplantation (allo-SCT) according to donor (D) and recipient (R) CMV serostatus. Seventy-five patients underwent allo-SCT from June 2010 to July 2012. The risk of CMV infection according to D and R serostatus was defined as follows: high risk (HR) (D-/R+), intermediate risk (IR) (D+/R+ and D+/R-) and low risk (LR) (D-/R-). Forty-five patients (60%) developed CMV infection and forty-six patients (61%) received steroids (PDN ≥ 1 mg/kg/day) to treat acute Graft versus host disease (GvHD). CMV infection was more common in those treated with steroids than in those not treated with steroids (70% vs. 44%, respectively, p<0.05). Overall, 40% of patients had recurrent CMV infection (50% PDN vs. 24% no PDN, p< 0.05). Steroids had no impact on the on the incidence of CMV infection or its recurrence in HR patients; however steroids did prolong the need of antiviral treatment. The incidence of CMV infection in IR patients was higher in those receiving PDN (80% PDN vs. 41% no PDN, p=0.01); recurrence rates were also higher (55% PDN vs. 18% no PDN, p= 0.02). We analyzed CMV-specific immune reconstitution in the first 22 patients of the serie and we observed that patients on steroids had lower levels of CMV specific lymphocytes TCD8 (p<0.05 on days +60, +100 and +180); and that CMV specific immune reconstitution (defined as lymphocytes CD8/IFN ≥ 1 cell/microl) was achieved later (after day +100 post-SCT) in steroid group.
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9.
Efficacy and Safety of a Preemptive Antiviral Therapy Strategy Based on Combined Virological and Immunological Monitoring for Active Cytomegalovirus Infection in Allogeneic Stem Cell Transplant Recipients
Navarro, D., Amat, P., de la Camara, R., Lopez, J., Vazquez, L., Serrano, D., Nieto, J., Rovira, M., Pinana, J. L., Gimenez, E., et al
Open Forum Infectious Diseases. 2016;3(2):ofw107
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Abstract
Background. Preemptive antiviral therapy for active cytomegalovirus (CMV) infection in allogeneic stem cell transplant recipients (Allo-SCT) results in overtreatment and a high rate of recurrences. Monitoring of CMV-specific T-cell immunity may help to individualize treatments and minimize these problems. Methods. We conducted a prospective, multicenter, matched comparison-group study to evaluate the efficacy and safety of a novel strategy that consisted of interrupting anti-CMV therapy upon CMV DNAemia clearance and concurrent detection of phosphoprotein 65/immediate-early-1-specific interferon-gamma-producing CD8(+) T cells at levels of >1 cell/micro L (within 30 days after the initiation of therapy). Immunological monitoring was performed on days +7, +14, +21, and +28 after treatment initiation. The primary endpoint was the cumulative incidence of recurrent DNAemia within 2 months after treatment cessation. Secondary endpoints were the length of antiviral treatment courses and the incidence of hematological toxicity. Results. Sixty-one patients were enrolled in the study group. Fifty-six patients were included in the matched-control group. Eleven patients (18%) fulfilled the criteria for antiviral treatment interruption. The cumulative incidence of recurrent CMV DNAemia was significantly lower (P = .02) in these patients than in patients in the comparative groups. Likewise, the length of antiviral treatment courses was significantly shorter in these patients than that in patients in the matched-control group (P = .003). No significant differences in the incidence of hematological toxicity was observed between the comparative groups. Conclusions. Our data support the clinical utility of combining immunological and virological monitoring for the management of CMV infection in a subset of Allo-SCT recipients.