scholarly journals Assessment of CMV T-Cell Immunity Post Allogeneic Hematopoietic Cell Transplantation Allow Stratification of Patients at Risk for CMV Infection

2018 ◽  
Vol 24 (3) ◽  
pp. S431-S432
Author(s):  
Liselotte Brix ◽  
Paul K. Wallace ◽  
Joseph D. Tario ◽  
Michelle E. DeLelys ◽  
Frederick I. Preffer ◽  
...  
Keyword(s):  
At Risk ◽  
T Cell ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
T Cell Immunity ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Cmv Infection ◽  
Cell Immunity ◽  
Patients At Risk

scholarly journals The impact of regulatory T cells on T-cell immunity following hematopoietic cell transplantation

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 945-953 ◽  
Author(s):  
Vu H. Nguyen ◽  
Sumana Shashidhar ◽  
Daisy S. Chang ◽  
Lena Ho ◽  
Neeraja Kambham ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
T Cell Immunity ◽  
Secondary Response ◽  
Cell Immunity ◽  
The Impact

Regulatory T cells (Tregs) prevent graft-versus-host disease (GvHD) by inhibiting the proliferation and function of conventional T cells (Tcons). However, the impact of Tregs on T-cell development and immunity following hematopoietic cell transplantation (HCT) is unknown. Using a murine GvHD model induced by Tcons, we demonstrate that adoptive transfer of Tregs leads to (1) abrogration of GvHD, (2) preservation of thymic and peripheral lymph node architecture, and (3) an accelerated donor lymphoid reconstitution of a diverse TCR-Vβ repertoire. The resultant enhanced lymphoid reconstitution in Treg recipients protects them from lethal cytomegalovirus (MCMV) infection. By contrast, mice that receive Tcons alone have disrupted lymphoid organs from GvHD and remain lymphopenic with a restricted TCR-Vβ repertoire and rapid death on MCMV challenge. Lymphocytes from previously infected Treg recipients generate secondary response specific to MCMV, indicating long-term protective immunity with transferred Tregs. Thymectomy significantly reduces survival after MCMV challenge in Treg recipients compared with euthymic controls. Our results indicate that Tregs enhance immune reconstitution by preventing GvHD-induced damage of the thymic and secondary lymphoid microenvironment. These findings provide new insights into the role of Tregs in affording protection to lymphoid stromal elements important for T-cell immunity.

scholarly journals Regulatory T cells promote alloengraftment in a model of late-gestation in utero hematopoietic cell transplantation

2020 ◽  
Vol 4 (6) ◽  
pp. 1102-1114
Author(s):  
John S. Riley ◽  
Lauren E. McClain ◽  
John D. Stratigis ◽  
Barbara E. Coons ◽  
Nicholas J. Ahn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
In Utero ◽  
Hematopoietic Cell ◽  
T Cell Immunity ◽  
Late Gestation ◽  
Cell Immunity

Abstract In utero hematopoietic cell transplantation (IUHCT) has the potential to cure congenital hematologic disorders including sickle cell disease. However, the window of opportunity for IUHCT closes with the acquisition of T-cell immunity, beginning at approximately 14 weeks gestation, posing significant technical challenges and excluding from treatment fetuses evaluated after the first trimester. Here we report that regulatory T cells can promote alloengraftment and preserve allograft tolerance after the acquisition of T-cell immunity in a mouse model of late-gestation IUHCT. We show that allografts enriched with regulatory T cells harvested from either IUHCT-tolerant or naive mice engraft at 20 days post coitum (DPC) with equal frequency to unenriched allografts transplanted at 14 DPC. Long-term, multilineage donor cell chimerism was achieved in the absence of graft-versus-host disease or mortality. Decreased alloreactivity among recipient T cells was observed consistent with donor-specific tolerance. These findings suggest that donor graft enrichment with regulatory T cells could be used to successfully perform IUHCT later in gestation.

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

2021 ◽  
pp. 107815522110604
Author(s):  
Kelly G Hawks ◽  
Amanda Fegley ◽  
Roy T Sabo ◽  
Catherine H Roberts ◽  
Amir A Toor
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Cmv Infection ◽  
Allogeneic Hct ◽  
Clinically Significant ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Introduction Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. Methods In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. Results Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. Conclusion Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.

Clinical and economic impact of treated CMV infection in adult CMV‐seropositive patients after allogeneic hematopoietic cell transplantation

2020 ◽  
Vol 92 (12) ◽  
pp. 3665-3673
Author(s):  
Régis Peffault De Latour ◽  
Patrice Chevallier ◽  
Didier Blaise ◽  
Sarah Alami ◽  
Laurie Lévy‐Bachelot ◽  
...  
Keyword(s):  
Economic Impact ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Cmv Infection

scholarly journals Donor-Derived CD4+ T Cells and Human Herpesvirus 6B Detection After Allogeneic Hematopoietic Cell Transplantation

2020 ◽  
Author(s):  
Derek J Hanson ◽  
Hu Xie ◽  
Danielle M Zerr ◽  
Wendy M Leisenring ◽  
Keith R Jerome ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Transplantation ◽  
Cd4 T Cells ◽  
Hematopoietic Cell Transplantation ◽  
Mononuclear Cells ◽  
Human Herpesvirus ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Peripheral Blood Mononuclear

Abstract We sought to determine whether donor-derived human herpesvirus (HHV) 6B–specific CD4+ T-cell abundance is correlated with HHV-6B detection after allogeneic hematopoietic cell transplantation. We identified 33 patients who received HLA-matched, non–T-cell–depleted, myeloablative allogeneic hematopoietic cell transplantation and underwent weekly plasma polymerase chain reaction testing for HHV-6B for 100 days thereafter. We tested donor peripheral blood mononuclear cells for HHV-6B–specific CD4+ T cells. Patients with HHV-6B detection above the median peak viral load (200 copies/mL) received approximately 10-fold fewer donor-derived total or HHV-6B–specific CD4+ T cells than those with peak HHV-6B detection at ≤200 copies/mL or with no HHV-6B detection. These data suggest the importance of donor-derived immunity for controlling HHV-6B reactivation.

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