scholarly journals Cytomegalovirus (CMV) Disease Despite Weekly Preemptive CMV Strategy for Recipients of Solid Organ and Hematopoietic Stem Cell Transplantation

2018 ◽  
Vol 5 (5) ◽  
Author(s):  
I P Lodding ◽  
C da Cunha Bang ◽  
S S Sørensen ◽  
F Gustafsson ◽  
M Iversen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Lung Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Screening Intervals ◽  
Lung Transplant Recipients ◽  
Cmv Disease ◽  
Cmv Dnaemia

Abstract Background Transplant recipients presenting with cytomegalovirus (CMV) disease at the time of diagnosis of CMV DNAemia pose a challenge to a preemptive CMV management strategy. However, the rate and risk factors of such failure remain uncertain. Methods Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients with a first episode of CMV polymerase chain reaction (PCR) DNAemia within the first year posttransplantation were evaluated (n = 335). Patient records were reviewed for presence of CMV disease at the time of CMV DNAemia diagnosis. The distribution and prevalence of CMV disease were estimated, and the odds ratio (OR) of CMV disease was modeled using logistic regression. Results The prevalence of CMV disease increased for both SOT and HSCT with increasing diagnostic CMV PCR load and with screening intervals >14 days. The only independent risk factor in multivariate analysis was increasing CMV DNAemia load of the diagnostic CMV PCR (OR = 6.16; 95% confidence interval, 2.09–18.11). Among recipients receiving weekly screening (n = 147), 16 (10.8%) had CMV disease at the time of diagnosis of CMV DNAemia (median DNAemia load 628 IU/mL; interquartile range, 432–1274); 93.8% of these cases were HSCT and lung transplant recipients. Conclusions Despite application of weekly screening intervals, HSCT and lung transplant recipients in particular presented with CMV disease at the time of diagnosis of CMV DNAemia. Additional research to improve the management of patients at risk of presenting with CMV disease at low levels of CMV DNAemia and despite weekly screening is warranted.

Functional Comparison and Longitudinal Assessment of Tri-Functional T-Cells Recognizing CMV pp65 and IE-1 Polypeptides in Hematopoietic Stem Cell and Solid Organ Transplant Recipients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2936-2936
Author(s):  
Don J. Diamond ◽  
Simon F. Lacey ◽  
Corinna La Rosa ◽  
Wendy Zhou ◽  
Ghislaine Gallez-Hawkins ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Specific Ctls ◽  
Tnf Α ◽  
Ifn Γ ◽  
Cmv Disease

Abstract Reconstitution of adaptive T-cell responses to human cytomegalovirus (CMV) is critical to protection from CMV disease following hematopoietic stem cell (HSCT) or solid organ transplantation (SOT). However, there is an incomplete understanding of which CMV antigens and epitopes are most crucial to providing protective responses. The functional status of cytotoxic T-lymphocyte (CTL) populations recognizing cytomegalovirus IE-1 and pp65 polypeptides was investigated in PBMC from either HSCT or SOT recipients. Our previous finding of differing levels of degranulation between CMV IE1 and pp65/pp50 specific T-cells was complicated by the possibility that differences were epitope and/or HLA-specific. We generalized the approach using a combined flow-based CD107a/b degranulation/mobilization and intracellular cytokine (ICC) assays using peptide libraries as antigens. These assays indicated that a significantly higher proportion of pp65-specific CTLs were in a more mature functional state compared to IE-1-specific CTLs. Degranulation/multicytokine ICC assays also indicated that a significantly higher proportion of the pp65-specific versus IE-1-specific CTLs secreted both IFN-γ and TNF-α, in addition to possessing greater cytotoxic potential. These results support our earlier findings of functional differences between CTLs recognizing individual epitopes within the IE-1 and pp65 antigens in HSCT recipients, and extend them to a broader array of HLA-restricted responses to those antigens. A report that a subset of HIV-1 specific CTLs capable of producing both IFN-γ and TNF-α was associated with improved cytotoxic activity prompted us to investigate whether degranulation, a functional correlate of cytotoxicity, was positively associated with dual cytokine production and predicted differences between IE1 and pp65-specific CD8+ T-cells. A higher proportion of pp65-specific compared to IE1-specific T-cells were present in the trifunctional IFN-γ+,TNF-α+, CD107+ population (p=0.008) in HSCT recipients. We have extended these findings to investigate the role of donor CMV status in terms of functional maturity of CMV-specific T cell response in transplant recipients. T cell maturation/function may act as a mechanistic correlate to the survival advantage of recipients receiving a stem-cell graft from CMV sero-positive donors. These principles have also been applied to investigations of a high risk population of sero-negative recipients of a sero-positive liver allograft. Data from this study will also be reviewed in the context of the model of trifunctional T cells being indicative of enhanced protective capacity against CMV disease and associated with survival.

scholarly journals Low-Dose Valganciclovir for CMV Prophylaxis after Lung Transplantation

2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
Hargobind S. Khurana ◽  
Alison Kole ◽  
Jeremy Falk ◽  
Sara Ghandehari ◽  
Guy Soohoo ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Lung Transplant ◽  
Low Dose ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Female Ratio ◽  
Oral Valganciclovir ◽  
Lung Transplant Recipients ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Purpose. Cytomegalovirus (CMV) remains an important pathogen following solid organ transplantation (SOT). Universal prophylaxis for CMV is adopted by most centers after lung transplantation. Various combinations studied for CMV prophylaxis include intravenous and oral ganciclovirs, oral valganciclovir, and CMV immunoglobulins. We present our experience with a low-dose of oral valganciclovir for CMV prophylaxis following lung transplantation. Methods and Materials. Our center started using 450 mg of daily oral valganciclovir for CMV prophylaxis in lung transplant recipients in Jan, 2001. A retrospective chart analysis of patients who underwent lung transplantation from January 2001 to December 2006 was done. Of 46 patients, 4 were excluded as they died within 30 days of transplant from postop complications. The mean age at transplant was 64 years, mostly single lung transplants (36/6) with a male-to-female ratio of 25/17. COPD was the most common reason for transplant (65%), and the serological CMV status of donors (D) and recipients (R) was as follows: D+/R+ 28, D+/R− 5, D−/R+ 5, and D−/R− 4. Valganciclovir was given for a total of 6 months posttransplant except for D−/R+ patients who received it for 12 months. Results. Five patients (12%) developed CMV disease with an average followup of 26 months. Only 2 (4.7%) developed CMV disease within six months of completing valganciclovir prophylaxis. This incidence is not significantly different from the best-reported results of CMV prophylaxis in lung transplant recipients. The remaining 3 patients developed the disease later in their course, one as late as 32 months posttransplant. The main side effects noted include leucopenia, neutropenia, and GI disturbances. However, the number of patients who had to temporarily stop or discontinue the medication (9.5%) was significantly lower than that reported in previous studies. Conclusions. Our experience suggests that low-dose valganciclovir is an effective method of prophylaxis for CMV disease in high-risk patients. It is a simple regimen that seems to have a better side effect profile and to improve patient compliance.

scholarly journals Tuberculosis in Pediatric Solid Organ and Hematopoietic Stem Cell Recipients

2021 ◽  
Vol 8 ◽  
pp. 2333794X2098154
Author(s):  
Melanie Dubois ◽  
Avika Dixit ◽  
Gabriella Lamb
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Clinical Presentation ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Limited Data ◽  
Hematopoietic Stem ◽  
Post Transplant

Children undergoing solid organ and hematopoietic stem cell transplantation are at high risk of morbidity and mortality from tuberculosis (TB) disease in the post-transplant period. Treatment of TB infection and disease in the post-transplant setting is complicated by immunosuppression and drug interactions. There are limited data that address the unique challenges for the management of TB in the pediatric transplant population. This review presents the current understanding of the epidemiology, clinical presentation, diagnosis, management, and prevention for pediatric transplant recipients with TB infection and disease. Further studies are needed to improve diagnosis of TB and optimize treatment outcomes for these patients.

scholarly journals Comparison of Standardized Cytomegalovirus (CMV) Viral Load Thresholds in Whole Blood and Plasma of Solid Organ and Hematopoietic Stem Cell Transplant Recipients with CMV Infection and Disease

2017 ◽  
Vol 4 (3) ◽  
Author(s):  
M Veronica Dioverti ◽  
Brian D Lahr ◽  
Jeffrey J Germer ◽  
Joseph D Yao ◽  
Michelle L Gartner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Viral Load ◽  
Hematopoietic Stem Cell ◽  
Whole Blood ◽  
Asymptomatic Infection ◽  
Solid Organ ◽  
Cell Transplant ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Cmv Disease

Abstract Background Quantification of cytomegalovirus (CMV) deoxyribonucleic acid (DNA) has important diagnostic, prognostic, and therapeutic implications in the management of transplant recipients. We aimed to assess a viral load in plasma and whole blood that distinguishes CMV disease from asymptomatic infection in a cohort of solid organ and hematopoietic stem cell transplantation. Methods We prospectively measured and compared CMV viral load in paired plasma and whole blood samples collected from transplant recipients with CMV infection and disease. Cytomegalovirus viral loads were determined by a commercially available US Food and Drug Administration-approved quantitative assay (COBAS AmpliPrep/COBAS TaqMan CMV Test [CAP/CTM CMV]) calibrated to the first World Health Organization International Standard for CMV DNA quantification. Results Moderate agreement of CMV viral load was observed between plasma and whole blood, with 31% of samples having discordant findings, particularly among samples with low DNA levels. Among the subset of samples where both paired samples had quantifiable levels, we observed a systematic bias that reflected higher viral load in whole blood compared with plasma. Based on receiver operating curve analysis, an initial plasma CMV viral load threshold of 1700 IU/mL in solid organ transplant recipients (sensitivity 80%, specificity 74%) and 1350 IU/mL in allogeneic hematopoietic stem cell transplant recipients (sensitivity 87%, specificity 87%) distinguished CMV disease and asymptomatic infection. Conclusions This study identifies standardized viral load thresholds that distinguish CMV disease from asymptomatic infection using CAP/CTM CMV assay. We propose these thresholds as potential triggers to be evaluated in prospective studies of preemptive therapy. Plasma was better than whole blood for measuring viral load using the CAP/CTM CMV assay.

CD26 expression on donor harvest as a risk predictive biomarker for developing Graft-versus-Host Disease post-Allogeneic Hematopoietic Stem Cell Transplantation: A tenyear followup study

2021 ◽  
pp. 1-12
Author(s):  
Sachin Punatar ◽  
Shruti Kandekar ◽  
Navin Khattry ◽  
Anant Gokarn ◽  
Kumar Prabhash ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Clinical Outcomes ◽  
Graft Versus Host Disease ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Cd34 Cells ◽  
Cd26 Expression

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (ASCT) is the preferred treatment option for patients with several hematologic disorders and immunodeficiency syndromes. Graft versus host disease (GVHD) is an immune mediated post-transplant complication which has a major impact on long term transplant outcomes. OBJECTIVE: Current efforts are focused on identification of new markers that serve as potential predictors of GVHD and other post-transplant clinical outcomes. METHODS: This study includes donor harvests collected from twenty-three allogeneic donors during period 2008–2009 and respective transplant recipients followed for clinical outcomes till March 2019. Percent CD26+ and CD34+ cells in donor harvest were analyzed using flow cytometry. Percent expression and infused dose of CD26+ and CD34+ cells were evaluated for association with various clinical outcomes. RESULTS: Total 23 healthy donors 28 years (13 males), and transplant recipients with median age 24 years (17 males) formed the study cohort. The diagnosis included malignant (n= 13) and non-malignant (n= 10) disorders. Median CD34brCD45lo HSC expression was 057% (IQR 024–103) while median CD26 expression was 1964% (IQR 896–3356) of all nucleated cells. CD26 expression was associated with donor age (P= 0.37). CD26 percent expression correlated with WBC engraftment (P= 0.015) and with acute GVHD (P= 0.023) whereas infused CD26 cell dose correlated with WBC engraftment (P= 0.004) and risk of CMV reactivation (P= 0.020). There was no statistically significant correlation of either CD26 expression or cell dose with chronic GVHD, EFS or OS.

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