scholarly journals Regulatory T Cell Therapy of Graft-versus-Host Disease: Advances and Challenges

2021 ◽  
Vol 22 (18) ◽  
pp. 9676
Author(s):  
Mehrdad Hefazi ◽  
Sara Bolivar-Wagers ◽  
Bruce R. Blazar
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Graft Versus Host Disease ◽  
Immune Homeostasis ◽  
Clinical Safety ◽  
Future Directions ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft-versus-host disease (GVHD) is the leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Immunomodulation using regulatory T cells (Tregs) offers an exciting option to prevent and/or treat GVHD as these cells naturally function to maintain immune homeostasis, can induce tolerance following HSCT, and have a tissue reparative function. Studies to date have established a clinical safety profile for polyclonal Tregs. Functional enhancement through genetic engineering offers the possibility of improved potency, specificity, and persistence. In this review, we provide the most up to date preclinical and clinical data on Treg cell therapy with a particular focus on GVHD. We discuss the different Treg subtypes and highlight the pharmacological and genetic approaches under investigation to enhance the application of Tregs in allo-HSCT. Lastly, we discuss the remaining challenges for optimal clinical translation and provide insights as to future directions of the field.

scholarly journals Effect of Early Post-Transplantation Tacrolimus Concentration on the Risk of Acute Graft-Versus-Host Disease in Allogenic Stem Cell Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 613
Author(s):  
Nidhi Sharma ◽  
Qiuhong Zhao ◽  
Bin Ni ◽  
Patrick Elder ◽  
Marcin Puto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Tacrolimus Concentration ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
The Impact ◽  
Risk Of Relapse ◽  
Acute Graft

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.

scholarly journals A Novel Secondary Neoplasm Following Allogeneic Hematopoietic Stem Cell Transplant: Mixed Donor-Recipient Primitive Mesenchymal Proliferation of the Liver

2021 ◽  
pp. 109352662110016
Author(s):  
Brian Earl ◽  
Zi Fan Yang ◽  
Harini Rao ◽  
Grace Cheng ◽  
Donna Wall ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Post Transplant

Post-hematopoietic stem cell transplant secondary solid neoplasms are uncommon and usually host-derived. We describe a 6-year-old female who developed a mixed donor-recipient origin mesenchymal stromal tumor-like lesion in the liver following an unrelated hematopoietic stem cell transplant complicated by severe graft-versus-host disease. This lesion arose early post-transplant in association with hepatic graft-versus-host disease. At 12 years post-transplant, the neoplasm has progressively shrunken in size and the patient remains well with no neoplasm-associated sequelae. This report characterizes a novel lesion of mixed origin post-transplant and offers unique insights into the contribution of bone marrow-derived cells to extra-medullary tissues.

A case of syngeneic graft-versus-host disease

2018 ◽  
Vol 25 (7) ◽  
pp. 1762-1766
Author(s):  
Sweta U Patel ◽  
Kendra Yum ◽  
Sara Kim ◽  
Luis M Isola ◽  
Eileen Scigliano ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
B Cell Lymphoma ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft-versus-host disease has been reported to occur rarely in syngeneic hematopoietic stem cell transplant recipients. Clinical and histological changes consistent with graft-versus-host disease have been reported to occur in this patient population. We report a case of a 46-year-old Caucasian male with diffuse large B-cell lymphoma in complete remission who underwent a syngeneic hematopoietic stem cell transplant. He was diagnosed with grade III acute skin and gastrointestinal graft-versus-host disease requiring high-dose corticosteroids and immunosuppressive therapy and resulting in a complete response. Syngeneic graft-versus-host disease is an anomaly that needs to be considered as a differential diagnosis of patients experiencing dermatitis, gastroenteritis, or hepatitis after an identical twin hematopoietic stem cell transplant.

scholarly journals Acute transaminitis as an atypical presentation of Graft-versus-Host Disease following Hematopoietic Stem Cell Transplantation

2019 ◽  
Vol 6 (1) ◽  
pp. 1
Author(s):  
Resham Ramkissoon ◽  
Akshay Shetty ◽  
Adam Doyle ◽  
Oyedele A. Adeyi ◽  
Keyur Patel
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Causative Drug ◽  
Initial Work ◽  
Work Up

Graft versus Host Disease (GVHD) can present with mucocutaneous, gastrointestinal and hepatic manifestations, specifically a cholestatic transaminitis. Rarely, some cases can present with only a hepatocellular transaminitis. Our patient presented with an acute hepatitis on day +90 post-hematopoietic stem cell transplant, without other overt manifestations of GVHD. The initial work up was negative for a viral etiology or causative drug, and the patient’s transaminases continued to rise. On day +96, an erythematous rash appeared with biopsy indicating lymphocytic and eosinophilic infiltrates concerning for cutaneous GVHD. Subsequently, a liver biopsy was obtained, and showed marked ductopenia with cholestasis, consistent with hepatic GVHD. 

scholarly journals Acute and chronic graft versus host disease after hematopoietic stem cell transplant

JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 53-66
Author(s):  
Vaneuza A. M. Funke ◽  
Maria Claudia Rodrigues Moreira ◽  
Afonso Celso Vigorito
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Primary Therapy ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft versus host disease is one of the main complications of Hematopoietic stem cell, in­volving about 50% to 80% of the patients. Acute GVHD clinical manifestations and therapy is discussed, as well as new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both refractory chronic and acute GVHD is an important field of discussion once there is no superiority for the majority of the agents after primary therapy has failed. Hence, this review is meant to be a useful tool of consultation for clinicians who are dealing with this complex complication.

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