The Pathophysiology of Graft‐Vs.‐Host Disease

Ferrara, James L.M.; Antin, Joseph H.

doi:10.1002/9780470987070.ch27

Cited by 30 publications

(26 citation statements)

References 284 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[2][3][4] Experimental and clinical data support the hypothesis that immune dysregulation during GVHD occurs in distinct phases 3 involving diffuse damage and inflammation from conditioning regimens, activation of donor T cells by host-derived antigen-presenting cells, [5][6][7] and target organ injury by soluble and cellular effectors. Since its inception, components of this paradigm have been challenged and refined.…”

Section: Introductionmentioning

confidence: 72%

Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

Askew

Pareek

Eid

et al. 2017

Blood

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 72%

Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

Askew

Pareek

Eid

et al. 2017

Blood

View full text Add to dashboard Cite

show abstract

“…The GVHD prevention mechanisms in recipients conditioned with anti-CD3 alone, which include confining of donor T cells to host lymphohematological tissues and tolerizing the residual alloreactive donor T cells, was reported in our previous publication (10). It is not surprising that the addition of SAHA to the anti-CD3-conditioning regimen did not lead to induction of GVHD, even though SAHA is a chemoreagent, because unlike traditional chemoreagents that cause host tissue damage and release of proinflammatory cytokines and chemokines (1,4), SAHA inhibits the tissue release of the proinflammatory cytokines and chemokines (16)(17)(18). In addition, HDAC inhibitors similar to SAHA have been shown to augment the generation and function of FoxP3 ϩ regulatory T (Treg) cells (26) and modulate APC function to down regulate Th1 differentiation (27).…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that TBI and high-dose chemotherapy conditioning play a critical role in initiating GVHD (4). The conditioning procedures cause tissue damage, release of proinflammatory cytokines and chemokines, and activation of host antigen-presenting cells (APCs), resulting in a proinflammatory cascade and donor alloreactive T cell infiltration of GVHD target tissues (5)(6)(7).…”

mentioning

confidence: 99%

HDAC inhibitor reduces cytokine storm and facilitates induction of chimerism that reverses lupus in anti-CD3 conditioning regimen

Zhao

Kirschbaum

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In allogeneic hematopoietic cell transplantation (HCT), donor T cellmediated graft versus host leukemia (GVL) and graft versus autoimmune (GVA) activity play critical roles in treatment of hematological malignancies and refractory autoimmune diseases. However, graft versus host disease (GVHD), which sometimes can be fatal, remains a major obstacle in classical HCT, where recipients are conditioned with total body irradiation or high-dose chemotherapy. We previously reported that anti-CD3 conditioning allows donor CD8 ؉ T cells to facilitate engraftment and mediate GVL without causing GVHD. However, the clinical application of this radiation-free and GVHD preventative conditioning regimen is hindered by the cytokine storm syndrome triggered by anti-CD3 and the high-dose donor bone marrow ( anti-CD3 mAb ͉ graft versus host disease ͉ hematopoietic cell transplantation ͉ systemic lupus erythematosus ͉ suberoylanilide hydroxamic acid

show abstract

“…Patients with sickle cell disease have high circulating levels of inflammatory cytokines, especially endothelin-1 and TNF alpha. 26 These are inflammatory cytokines which are likely to contribute to the onset of GVHD syndromes 27 and may explain why patients with sickle cell disease may be at higher risk for GVHD than are other patients. Whatever the etiology, our observations indicate that GVHD constitutes a major risk in adults undergong allogeneic stem cell transplantation sickle cell disease.…”

Section: Discussionmentioning

confidence: 99%

Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease

Besien

Bartholomew

Stock

et al. 2000

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:Although allogeneic transplantation can be curative for patients with sickle cell disease, the toxicity of conditioning regimens has precluded its use in adults with significant end-organ damage. Newer conditioning regimens have been developed that are less toxic and that may broaden the applicability of allogeneic transplantation in this disorder. We report two adults with end-stage sickle cell disease, who underwent allogeneic transplantation from an HLA-identical sibling donor after conditioning with fludarabine/melphalan and ATG. Both patients had been extensively transfused and one had multiple RBC antibodies. One of the patients also had end-stage renal disease, and was dialysis dependent. Engraftment occurred promptly in both patients. Both achieved 100% donor chimerism and both were free of pain crises after transplant. The first patient died of a respiratory failure related to chronic graft-versushost disease (GVHD) on day 335 after transplantation. The second patient developed severe gastro-intestinal GVHD and TTP and died on day 147 after transplantation. Conditioning with fludarabine/melphalan and ATG followed by allogeneic stem cell transplantation resulted in prompt and reliable engraftment in adults with end-stage sickle cell disease. The incidence of severe GVHD was unacceptably high and may be related to the ethnicity of the patients or to the inflammatory state associated with pre-existing sickle cell disease. Bone Marrow Transplantation (2000) 26, 445-449.

show abstract

The Pathophysiology of Graft‐Vs.‐Host Disease

Cited by 30 publications

References 284 publications

Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

Cyclin-dependent kinase 5 activity is required for allogeneic T-cell responses after hematopoietic cell transplantation in mice

HDAC inhibitor reduces cytokine storm and facilitates induction of chimerism that reverses lupus in anti-CD3 conditioning regimen

Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease

Contact Info

Product

Resources

About