scholarly journals Adenovirus Viral Kinetics and Mortality in Ex Vivo T Cell-Depleted Hematopoietic Cell Transplant Recipients With Adenovirus Infection From a Single Center

2020 ◽  
Vol 222 (7) ◽  
pp. 1180-1187
Author(s):  
Yeon Joo Lee ◽  
Jiaqi Fang ◽  
Phaedon D Zavras ◽  
Susan E Prockop ◽  
Farid Boulad ◽  
...  
Keyword(s):  
T Cell ◽  
Ex Vivo ◽  
Area Under The Curve ◽  
Absolute Lymphocyte Count ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Viral Kinetics ◽  
Cox Models ◽  
Viral Loads

Abstract Background We report on predictors of adenovirus (ADV) viremia and correlation of ADV viral kinetics with mortality in ex vivo T-cell depleted (TCD) hematopoietic cell transplant (HCT). Methods T cell-depleted HCT recipients from January 1, 2012 through September 30, 2018 were prospectively monitored for ADV in the plasma through Day (D) +100 posttransplant or for 16 weeks after the onset of ADV viremia. Adenovirus viremia was defined as ≥2 consecutive viral loads (VLs) ≥1000 copies/mL through D +100. Time-averaged area under the curve (AAUC) or peak ADV VL through 16 weeks after onset of ADV viremia were explored as predictors of mortality in Cox models. Results Of 586 patients (adult 81.7%), 51 (8.7%) developed ADV viremia by D +100. Age <18 years, recipient cytomegalovirus seropositivity, absolute lymphocyte count <300 cells/µL at D +30, and acute graft-versus-host disease were predictors of ADV viremia in multivariate models. Fifteen (29%) patients with ADV viremia died by D +180; 8 of 15 (53%) died from ADV. Peak ADV VL (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.52–3.33) and increasing AAUC (HR, 2.95; 95% CI, 1.83–4.75) correlated with mortality at D +180. Conclusions In TCD HCT, peak ADV VL and ADV AAUC correlated with mortality at D +180. Our data support the potential utility of ADV viral kinetics as endpoints in clinical trials of ADV therapies.

scholarly journals Viral Kinetics and Outcomes of Adenovirus Reactivation Following Allogeneic Hematopoietic Cell Transplant or CAR-T Cell Therapy

2020 ◽  
Vol 26 (3) ◽  
pp. S331
Author(s):  
Aditya Aniruddha Chandorkar ◽  
Anthony D. Anderson ◽  
Michele I. Morris ◽  
Yoichiro Natori ◽  
Krishna V. Komanduri ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Viral Kinetics ◽  
T Cell Therapy ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Impact of HHV-6 in Recipients of Ex Vivo T-Cell Depleted Hematopoietic Cell Transplant

2020 ◽  
Vol 26 (3) ◽  
pp. S338
Author(s):  
Yeon Joo Lee ◽  
Yiqi Su ◽  
Roni Tamari ◽  
Ann A. Jakubowski ◽  
Sergio A. Giralt ◽  
...  
Keyword(s):  
T Cell ◽  
Ex Vivo ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant

CMV viral load kinetics predict CMV end-organ disease and mortality after hematopoietic cell transplant (HCT)

2021 ◽  
Author(s):  
Anat Stern ◽  
Yiqi Su ◽  
Henry Dumke ◽  
Jiaqi Fang ◽  
Roni Tamari ◽  
...  
Keyword(s):  
Viral Load ◽  
Hematopoietic Cell Transplantation ◽  
Area Under The Curve ◽  
Hematopoietic Cell ◽  
Cancer Center ◽  
Cell Transplant ◽  
Elite Controllers ◽  
Hematopoietic Cell Transplant ◽  
Cox Models ◽  
One Year

Abstract Background We investigated the association between time-averaged area under the curve (AAUC) of CMV viral load (VL) by D100 and overall survival (OS) at one-year post-hematopoietic cell transplantation (HCT). Methods A retrospective cohort study, including patients receiving HCT between 2010.6 and 2017.12 from Memorial Sloan Kettering Cancer Center. AAUC was calculated for patients with detected VL. Patients were categorized into “non-controllers” (Q4) and “controllers” (Q1-3) using the highest AAUC quartile as cutoff. Kaplan-Meier analyses and Cox models were used to estimate the association between AAUC and OS. Patients with non-detected CMV VL were categorized into “elite-controllers” (R+ or R-/D+) and “R-/D-”. Results The study (N=952) included 282 controllers, 93 non-controllers, 275 elite-controllers, and 302 R-/D-. OS was 80.1% and 58.1% for controllers and non-controllers, respectively. In multivariable models, non-controllers had worse OS versus controllers (adjusted hazard ratio [HR] 2.65, 95% CI 1.71-4.12). In landmark analyses, CMV controllers had similar OS as elite-controllers (HR 1.26, 95% CI 0.83-1.91) or R-/D- (HR 0.98, 95% CI 0.64-1.5). Conclusion CMV non-controllers had worse OS at one-year post-HCT. CMV controllers had similar OS as elite-controllers or R-/D-. Future studies are needed to validate our AAUC cutoff across different cohorts and CMV management strategies.

Photopheresis in HIV-1 Infected Patients (Pt) Using Benzoporphyrin Derivative (BPD-MA) Induces Apoptosis in CD4 Cells, Increases Cytolytic T-Cell Activity, Intracellular Expression of Chemokines, and Decreases HIV Infectivity and Viral Load.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1257-1257
Author(s):  
Zale P. Bernstein ◽  
Thomas Dougherty ◽  
Stanley Schwartz ◽  
Sandra Gollnick ◽  
Carleton Stewart ◽  
...  
Keyword(s):  
Viral Load ◽  
Immune System ◽  
T Cell ◽  
Ex Vivo ◽  
Cell Activity ◽  
Area Under The Curve ◽  
Viral Control ◽  
Viral Loads ◽  
Hiv 1

Abstract HIV is able to elude both cellular and humoral arms of the immune system; thereby making viral control difficult. Extra corporeal photochemotherapy (ECP) or photopheresis is an immunomodulatory therapy in which lymphocytes are reinfused into the host after exposure to a photoactive compound and ultraviolet A light. It is an effective therapeutic approach to several disorders of the immune system including acute and chronic graft-versus-host disease, scleroderma, and cutaneous T-cell lymphoma. This process may offer a novel approach to viral control with minimal or no toxicity. We initiated an ex vivo and subsequently a clinical pilot trial utilizing Benzoporphyrin Derivative as the photosensitive compound. Ex vivo dosing studies identified the minimum energy levels of light exposure and concentrations of BPD that eradicated both cell-free and cell-associated HIV-1 infectivity without destroying the virus particles or infected leukocytes. Leukocytes so treated remained viable. They did demonstrate altered cytokine and chemokine expression with apoptosis induced in a minority of CD4 but not CD8 positive cells. Furthermore, there was a statistically significant increase in cytolytic T-cell activity expressed as percentage of granzyme-B release. A pilot in vivo, 24 week clinical trial in seven HIV-1 infected patients (all were required, upon entry, to have viral loads of > 10,000) using the photopheresis parameters established above demonstrated that the treatment was well tolerated and beneficial. Three individuals who had rapidly rising viral loads prior to initiating therapy stabilized once treatment began. Two of which had a (sustained) greater than .5 log decrement and 5 had stable plasma viral loads (less than a .5 log increment or decrement) with varied effects on absolute CD4 and CD8 positive lymphocytes counts. One subject achieved a greater than 1 log decrement in HIV-1 plasma viral load also developed undetectable in vivo cell-free and cell-associated HIV-1 infectivity while demonstrating an increased in vitro lymphocyte mitogen stimulation index. Subsequently, under amended and successor protocol 5 additional 12 month courses were administered to three additional patients and two of the previous enrollees. The area under the curve for viral load (viral load x # of weeks) for these twelve courses of therapy showed a significant decrease from pre to post therapy (p 0.007). There were no significant changes in CD4 or CD8 numbers area under the curve (CD4 number # of weeks and CD8 number x # of weeks). None of the subjects developed an AIDS defining illness during the course of therapy nor were there any treatment associated toxicities. These studies suggest that ECP augments activity of various arms of the immune system without any significant toxicity and may be effective in controlling HIV replication. We now plan a randomized Phase II study utilizing long-term photopheresis (twice monthly for 48 weeks) in addition to anti-retroviral therapy versus anti-retroviral therapy alone to further determine efficacy and mechanism of activity.

scholarly journals Recipient-specific T-cell repertoire reconstitution in the gut following murine hematopoietic cell transplant

2020 ◽  
Vol 4 (17) ◽  
pp. 4232-4243
Author(s):  
Pingping Zheng ◽  
John Tamaresis ◽  
Govindarajan Thangavelu ◽  
Liwen Xu ◽  
Xiaoqing You ◽  
...  
Keyword(s):  
T Cell ◽  
Hematopoietic Cell Transplantation ◽  
Cell Receptor ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Gi Tract ◽  
Hematopoietic Cell Transplant ◽  
Cell Repertoire ◽  
T Cell Reconstitution ◽  
Tcr Repertoire

Abstract Graft-versus-host disease (GVHD) is a complication of hematopoietic cell transplantation (HCT) caused by alloreactive T cells. Murine models of HCT are used to understand GVHD and T-cell reconstitution in GVHD target organs, most notably the gastrointestinal (GI) tract where the disease contributes most to patient mortality. T-cell receptor (TCR) repertoire sequencing was used to measure T-cell reconstitution from the same donor graft (C57BL/6 H-2b) in the GI tract of different recipients across a spectrum of matching, from syngeneic (C57BL/6), to minor histocompatibility (MHC) antigen mismatch BALB.B (H-2b), to major MHC mismatched B10.BR (H-2k) and BALB/c (H-2d). Although the donor T-cell pools had highly similar TCR, the TCR repertoire after HCT was very specific to recipients in each experiment independent of geography. A single invariant natural killer T clone was identifiable in every recipient group and was enriched in syngeneic recipients according to clonal count and confirmatory flow cytometry. Using a novel cluster analysis of the TCR repertoire, we could classify recipient groups based only on their CDR3 size distribution or TCR repertoire relatedness. Using a method for evaluating the contribution of common TCR motifs to relatedness, we found that reproducible sets of clones were associated with specific recipient groups within each experiment and that relatedness did not necessarily depend on the most common clones in allogeneic recipients. This finding suggests that TCR reconstitution is highly stochastic and likely does not depend on the evaluation of the most expanded TCR clones in any individual recipient but instead depends on a complex polyclonal architecture.

scholarly journals Cytomegalovirus Infection in Solid Organ and Hematopoietic Cell Transplantation: State of the Evidence

2020 ◽  
Vol 221 (Supplement_1) ◽  
pp. S23-S31 ◽  
Author(s):  
Ghady Haidar ◽  
Michael Boeckh ◽  
Nina Singh
Keyword(s):  
T Cell ◽  
Hematopoietic Cell Transplantation ◽  
Solid Organ Transplantation ◽  
Immune Monitoring ◽  
Hematopoietic Cell ◽  
Preemptive Therapy ◽  
Solid Organ ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Cell Transplant

Abstract This review focuses on recent advances in the field of cytomegalovirus (CMV). The 2 main strategies for CMV prevention are prophylaxis and preemptive therapy. Prophylaxis effectively prevents CMV infection after solid organ transplantation (SOT) but is associated with high rates of neutropenia and delayed-onset postprophylaxis disease. In contrast, preemptive therapy has the advantage of leading to lower rates of CMV disease and robust humoral and T-cell responses. It is widely used in hematopoietic cell transplant recipients but is infrequently utilized after SOT due to logistical considerations, though these may be overcome by novel methods to monitor CMV viremia using self-testing platforms. We review recent developments in CMV immune monitoring, vaccination, and monoclonal antibodies, all of which have the potential to become part of integrated strategies that rely on viral load monitoring and immune responses. We discuss novel therapeutic options for drug-resistant or refractory CMV infection, including maribavir, letermovir, and adoptive T-cell transfer. We also explore the role of donor factors in transmitting CMV after SOT. Finally, we propose a framework with which to approach CMV prevention in the foreseeable future.

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