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4yr
Treating Acute Graft vs Host Disease

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT)caused by donor T cellsthat respond to the host polymorphic histocompatibility antigens as foreign, leading to inflammation and immune-mediated injury of host tissues. Acute GVHD (aGVHD) usually manifests within 100 days following HSCT, while chronic GVHD (cGVHD) generally occurs after 100 days and, has some features of autoimmune diseases. Clinical manifestations of aGVHD include skin rash or erythema, gastrointestinal symptoms (diarrhea, nausea, cramping, bleeding) and liver symptoms (hyperbilirubinemia and elevated serum levels of liver enzymes). Similar symptoms may occur in cGVHD, as well as nail, scalp, buccal mucosa, eye, and internal organ damage.





First line treatment for GVHD is topical and systemic corticosteroids. However, ~50% of aGVHD patients become steroid refractory, and broad spectrum immunosuppressants are commonly added ‘off label’ to a steroid regimen, leading to long-term side effects. Other options for steroid-refractory aGVHD include ruxolitib, a protein kinase inhibitor specific for JAK1 and JAK2, extracorporeal photopheresis, and various off-label treatments.





Given the choices, data, and potential risks - how do you treat steroid-refractory aGVHD ?





References



• Abedin, S. and Hamadani, M., 2020. Experimental Pharmaceuticals for Steroid-Refractory Acute Graft-versus-Host Disease. J. Exp. Pharmacology, 12, pp. 549-557. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705269/



 



 


  • 4yr
    ruxolitinib, ibrutinib, rituximab, ECP, among others are all options for steroid refractory GvHD
  • 4yr
    Is there a way to risk stratify patients with steroid refractory GVHD? Do certain respond more favorably to ruxolitinib vs rituximab vs imbruvica ?
  • 4yr
    What long-term adverse effects are most concerning with respect to GVHD? How do you address these concerns from a therapeutic perspective?
  • 4yr
    The data for Ibrutinib are emerging and promising, and it is valuable to have other safe and effective options as well along with ruxolitinib
  • 4yr
    Ruxolitinib is the best available option for steroid refractory GVHD across different organs involvement, other helpful agents include MMF, ECP and others
  • 4yr
    i will use jakafi for seroid refractory GVHD
  • 4yr
    Ibrutinib and ruxolitinib can be used in steroid refractory GVHD.
  • 4yr
    Other than ECP, I prefer ruxolitinib which is approved in this setting. Ibrutinib is also an option.
  • 4yr
    I have had the best results over all with ruxolitinib. Other agents such as Imbruvica or Gleevec may be effective. You always have to deal with potential side effects.
  • 4yr
    Start jakafi asap, as soon as diagnosis of SR aGVHD is made.
  • 4yr
    1. Jakafi ( ruxolitinib) recently approved for acute steroid refractory GVHD- with responses in all organs, irrespective of the grade/severity of disease
    2. Anemia/cytopenias can be a limiting factor- have started at a lower dose and then increased as tolerated, and supported with transfusions
    3. Agree with other comments- have used it in conjuction with tacrolimus, photophersis, cyclosporine, as well as rituximab
  • 4yr
    mostly using Jakafi for steroid refractory, mycophenolate and etanercept
  • 4yr
    I personally believe Jakafi is the treatment of choice; however, photophoresis, sirolimus, Imbruvica, ATG could all be good options; Personally Jakafi works well for skin and to certain extent liver and GI not so much for lung;
  • 4yr
    My first choice of therapy for steroid-refractory GvHD is Jakafi.
  • 4yr
    currently using ruxolitinib for steroid refractory GVHD; have also used Gleevec, Imbruvica, and Rituximab

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