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

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 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.

scholarly journals 940. The use of a commercially available CMV T Cell Immunity Panel to Assess the Risk of CMV Infections in Hematopoietic Cell Transplant Recipients with Low Level CMV Viremia

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S562-S564
Author(s):  
Fareed Khawaja ◽  
Carmen Sadaka ◽  
Samantha Trager ◽  
Kerri E Fernandes ◽  
Georgios Angelidakis ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Hematopoietic Cell ◽  
T Cell Immunity ◽  
Cell Transplant ◽  
Research Support ◽  
Hematopoietic Cell Transplant ◽  
Low Level ◽  
Cell Immunity ◽  
Cmv Reactivation

Abstract Background Cytomegalovirus (CMV) infections continue to be associated with increased morbidity and mortality in Hematopoietic Cell Transplant (HCT) recipients. Treatment of high risk patients with low level viremia may reduce overall duration of therapy and reduce complications. CMV T Cell Immunity Panel (TCIP) may help identify patients at high risk of CMV reactivation prior to developing clinically significant CMV infection (CS-CMVi). Our study aims to identify HCT recipients with low level CMV viremia who are at high risk of CMV reactivation with the use of CMV-TCIP while on or off letermovir for prophylaxis. Methods We enrolled in a prospective cohort study allogeneic HCT recipients (excluding cord blood transplantation) with low level of CMV viremia (viral load of < 1000 IU/ml) on no therapy, starting October 2019. CMV TCIP assay was performed at enrollment, weeks 1, 2, 3, 4, 6 and 8. CMV TCIP results were interpreted as negative or positive based on percentage of interferon gamma producing CD4+ or CD8+ CMV specific T cells. The primary endpoint was progression to a CS-CMVi. We are presenting the results of the first 30 patients with data up to 4 weeks from enrollment. Results Among the 30 patients, 73% were on letermovir for CMV prophylaxis. Majority of the patients were ≥ 40 years old (77%), male (63%), received transplant for AML (40%), were in complete remission at time of transplant (23%) and received cyclophosphamide (90%). The median time from transplant to enrollment was 77 days (IQR 37-172) (table 1). At enrollment, 10 (33%) patients had a positive CMV TCIP, 10 (33%) had a negative CMV TCIP, and 10 (33%) had an uninterpretable CMV TCIP result due to inability to quantify T cells (table 1). Four (13%) patients developed CS-CMVi; 3 of these patients had a negative TCIP and 1 had unquantifiable CMV TCIP (Figure 1). The mean percentage of CMV specific CD4+ and CD8+ interferon producing cells was 1.76% (SD 2.24) and 9.37% (SD 11.35) for those on letermovir and 2.09% (SD 2.05) and 3.97% (SD 5.24) off letermovir respectively (P >0.05) (Figure 2). Figure 1. Breakdown of the 30 patients during the 4 week follow up period Abbreviations: HCT: Hematopoietic cell transplantation; CMV: Cytomegalovirus; TCIP: T cell immunity panel Figure 2. Box-plot of percentage of CD4+ CMV specific interferon producing cells over time. Threshold for positive result (0.2%) marked. Abbreviations: CMV: Cytomegalovirus Table 1. Baseline characteristics of patients enrolled Abbreviations: CMV: Cytomegalovirus; TCIP: T cell immunity panel; IQR: Interquartile range Conclusion Our results demonstrate the value of the CMV TCIP in identifying high risk HCT recipients prior to developing CS-CMV infection. Disclosures Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Ella Ariza Heredia, MD, Merck (Grant/Research Support) Michelle Altrich, PhD, HCLD, Eurofins Viracor (Employee) Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support)

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