TNF-Inhibition with Etanercept for Graft-versus-Host Disease Prevention in High-Risk HCT: Lower TNFR1 Levels Correlate with Better Outcomes

Choi, Sung Won; Stiff, Patrick J.; Cooke, Kenneth R.; Ferrara, James L.M.; Braun, Thomas; Kitko, Carrie L.; Reddy, Pavan; Yanik, Gregory A.; Mineishi, Shin; Paczesny, Sophie; Hanauer, David A.; Pawarode, Attaphol; Peres, Edward; Rodriguez, Tulio E.; Smith, Scott E.; Levine, John E.

doi:10.1016/j.bbmt.2012.03.013

Cited by 50 publications

(41 citation statements)

References 35 publications

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“…TNF inhibition using etanercept led to reduced GVHD rates 37 ; however, the overall benefit from TNF inhibition in GVHD patients was limited. Because diet-based induction of miR-146a by DIM ameliorated GVHD, it is conceivable that the intestinal immune system may benefit from miR-146a induction.…”

Section: Discussionmentioning

confidence: 99%

MiR-146a regulates the TRAF6/TNF-axis in donor T cells during GVHD

Stickel

Prinz

Pfeifer

et al. 2014

Blood

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Section: Discussionmentioning

confidence: 99%

MiR-146a regulates the TRAF6/TNF-axis in donor T cells during GVHD

Stickel

Prinz

Pfeifer

et al. 2014

Blood

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“…With this in mind, it should be noted that no cytokine-inhibition strategy or cytokine administration has proved efficacious in randomized studies. In general, encouraging results seen in preclinical studies and early-phase clinical trials have either not progressed into phase III studies, or effects have not been robust within this context [e.g., IL-1 (82) and TNF inhibition (83,84)]. Table I provides a summary of cytokines and inhibitors that have been explored for Cytokines and their antagonists are included that have been tested within a trial setting to prevent or treat GVHD or other complications of allogeneic BMT.…”

Section: Translational Applicationmentioning

confidence: 99%

Cytokines in Graft-versus-Host Disease

Henden

Hill

2015

The Journal of Immunology

153

117

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Graft-versus-host disease (GVHD) is a complication of allogeneic bone marrow transplantation whereby transplanted naive and marrow-derived T cells damage recipient tissue through similar mechanisms to those that allow destruction of malignant cells, the therapeutic intent of bone marrow transplantation. The manifestations and severity of GVHD are highly variable and are influenced by the proportions of naive cells maturing along regulatory T cell, Th1, Th2, or Th17 phenotypes. This maturation is largely influenced by local cytokines, which, in turn, activate transcription factors and drive development toward a dominant phenotype. In addition, proinflammatory cytokines exert direct effects on GVHD target tissues. Our knowledge of the role that cytokines play in orchestrating GVHD is expanding rapidly and parallels other infective and inflammatory conditions in which a predominant T cell signature is causative of pathology. Because a broad spectrum of cytokine therapies is now routinely used in clinical practice, they are increasingly relevant to transplant medicine.

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“…Further, following myeloablative and even nonmyeloablative conditioning regimens, the magnitude of change in the TNF-receptor-1 (TNFR1; a good surrogate for TNF-α) ratio (day +7 after transplantation/pretransplantation baseline values) has been correlated with later occurrence of acute GVHD [55,56]. These observations prompted the development of clinical studies aimed at assessing the impact of TNF-α inhibition on GVHD prevention [57,58]. Unfortunately, administration of the TNF-α inhibitors infliximab (10 mg/kg one day prior to conditioning and then on days 0, +7, +14, +28, and +42) or etanercept (25 mg twice weekly from start of conditioning to day +56) in addition to standard GVHD prophylaxis failed to prevent acute GVHD [57,58].…”

Section: New Pharmacological Approachesmentioning

confidence: 99%

“…These observations prompted the development of clinical studies aimed at assessing the impact of TNF-α inhibition on GVHD prevention [57,58]. Unfortunately, administration of the TNF-α inhibitors infliximab (10 mg/kg one day prior to conditioning and then on days 0, +7, +14, +28, and +42) or etanercept (25 mg twice weekly from start of conditioning to day +56) in addition to standard GVHD prophylaxis failed to prevent acute GVHD [57,58].…”

Section: New Pharmacological Approachesmentioning

confidence: 99%

Thinking Out of the Box—New Approaches to Controlling GVHD

Baron

Humblet-Baron

Ehx

et al. 2014

Curr Hematol Malig Rep

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Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD prophylaxis regimens continue to be based on the combination of a calcineurin inhibitor with an antimetabolite, while first line treatments still rely on high-dose corticosteroids. Further, no second line treatment has emerged thus far in acute or chronic GVHD patients who failed to respond with corticosteroid treatment. After briefly reviewing current standards of GVHD prevention and treatment, this article will discuss recent approaches that might change GVHD prophylaxis/treatment for decades to come, with a special focus on recently developed immunoregulatory strategies based on infusion of mesenchymal stromal or regulatory T-cells, or injection of lowdose interleukin-2.

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TNF-Inhibition with Etanercept for Graft-versus-Host Disease Prevention in High-Risk HCT: Lower TNFR1 Levels Correlate with Better Outcomes

Cited by 50 publications

References 35 publications

MiR-146a regulates the TRAF6/TNF-axis in donor T cells during GVHD

MiR-146a regulates the TRAF6/TNF-axis in donor T cells during GVHD

Cytokines in Graft-versus-Host Disease

Thinking Out of the Box—New Approaches to Controlling GVHD

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