Graft-versus-host disease medical therapy
|
Graft-versus-host disease |
|
Differentiating Graft-versus-host disease from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Graft-versus-host disease medical therapy On the Web |
|
American Roentgen Ray Society Images of Graft-versus-host disease medical therapy |
|
Risk calculators and risk factors for Graft-versus-host disease medical therapy |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]
Overview
Medical Therapy
Corticosteroids, such as prednisone or methylprednisolone, are the standard of care in acute GVHD[1] and chronic GVHD. Prednisone is an oral steroids, and methylprednisolone is an intravenous steroid. Typical dose of methylprednisolone is 2 to 2.5 mg/kg daily.[2] The use of these corticosteroids is designed to suppress the T-cell mediated immune onslaught on the host tissues; however in high doses this immune-suppression raises the risk of infections and cancer relapse. Therefore it is desirable to taper off the post-transplant high level steroid doses to lower levels, at which point the appearance of mild GVHD may be welcome, especially in HLA mis-matched patients, as it is typically associated with a graft-versus-tumor effect. Steroids can be tapers quickly or slowly after the induction phase of steroids results in adequate response.
Other immunosuppressive agents that are typically used include cyclosporine and tacrolimus.[2] These are immunophilins that suppress T cell responses. Mycophenolate mofetil has been used for prophylaxis for GvHD.[2] Other modalities of therapy that have been used, besides oral or intravenous steroids or immunophilins, include ex vivo T cell depletion and in vivo T cell depletion.[2] The latter can be accomplished via anti-thymocyte globulin (ATG) or alemtuzumab.
For steroid-refractory GvHD, there are a few options available, though the data is not robust.
- Ruxolitinib: This is an inhibitor of Janus kinase 2 (JAK2), has been used.[3]
- Alemtuzumab: This is an antibody to CD52, which is found to lymphocytes. Alemtuzumab has been used in patients with chronic lymphocytic leukemia and T cell pro-lymphocytic leukemia.[3]
- mTOR inhibitors: These agents inhibitor the mammalian target of rapamycin. Everolimus is an mTOR inhibitor.[3]
- Rituximab: This is a monoclonal antibody to CD20, which is found on B cells. Rituximab is known for its immunomodulatory effects and is currently FDA-approved for non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, Wegener's granulomatosis, microscopic polyangitis, and immune thrombocytopenia purpura.[3]
- Anti-TNF agents: Examples of anti-TNF agents include etanercept and adalilumab. TNF is involved in the inflammatory response, so TNF blockade results in immunosuppression.[3]
References
- ↑ Goker H, Haznedaroglu IC, Chao NJ (2001). "Acute graft-vs-host disease: pathobiology and management". Exp. Hematol. 29 (3): 259–77. PMID 11274753.
- ↑ 2.0 2.1 2.2 2.3 Jacobsohn DA, Vogelsang GB (2007). "Acute graft versus host disease". Orphanet J Rare Dis. 2: 35. doi:10.1186/1750-1172-2-35. PMC 2018687. PMID 17784964.
- ↑ 3.0 3.1 3.2 3.3 3.4 Assouan D, Lebon D, Charbonnier A, Royer B, Marolleau JP, Gruson B (2017). "Ruxolitinib as a promising treatment for corticosteroid-refractory graft-versus-host disease". Br J Haematol. doi:10.1111/bjh.14679. PMID 28444730.