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Treatments > Graft versus Host Disease

Last update: 08/10/2013

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Comments on the News:

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* MNT 2013:

Biomarker (ST2) identified to predict Resistance to Treatment for Graft versus Host Disease
after allogeneic stem cell transplants http://bit.ly/19Slkyl

Thirty to 40 percent of stem cell transplant recipients whose donor is related will
experience graft-versus-host disease. The percentage could rise to 60 to 80 percent if the
patient and donor are not related.


Comment:  The improved risk stratification made possible by this marker -- predicting resistance
to GVHD treatment -- may allow for earlier evaluation of additional therapies before the development of resistant disease and better monitoring with preemptive and investigational interventions.   ~ KarlS
NEJM, 2013:

 ST2 as a Marker for Risk of Therapy-Resistant Graft-versus-Host Disease and Death http://www.nejm.org/doi/full/10.1056/NEJMoa1213299

Graft vs. Host Disease (GVHD) -  a frequent complication of allogeneic bone marrow transplant in which the engrafted donor cells attacks the patient's organs and tissue. GVHD tends to be more severe in patients receiving mismatched transplants from family member or unrelated donors. 

GVHD is two diseases: acute GVHD and chronic GVHD. "Patients may develop one, both or neither. Acute and chronic GVHD differ in their symptoms, clinical signs and time of onset." ~

Acute GVHD usually occurs during the first three months following an allogeneic BMT. "T-cells present in the donor's bone marrow at the time of transplant identify the BMT patient as "non-self' and attack the patient's skin, liver, stomach, and/or intestines. The earliest sign of acute GVHD is often a skin rash that usually first appears on the patient's hands and feet."  medicalistes.org

Chronic GVHD usually develops after the third month post-transplant. "Scientists believe that new T-cells produced after the donor's bone marrow has engrafted in the patient may cause chronic GVHD. Most patients with chronic GVHD experience skin problems that may include a dry itching rash, a change in skin color, and tautness or tightening of the skin. Partial hair loss or premature graying may also occur."  medicalistes.org

Illustrations of processes  Acute and Chronic GVHD graphics

More detail: "Chronic graft-versus-host disease (GVHD) is the most serious and common long-term complication of allogeneic hematopoietic stem cell transplantation (HCT), occurring in 20% to 70% of people surviving more than 100 days.1,2 Approximately half of affected people have 3 or more involved organs, and treatment typically requires immunosuppressive medications for a median of 1 to 3 years. Because of higher treatment-related (nonrelapse) mortality, chronic GVHD remains the major cause of late death despite its association with a lower relapse rate.3,4bloodjournal.org

Many risk factors exist that can predispose patients to chronic GVHD. These include: 
• prior acute GVHD • older donor/recipient age • HLA mismatch • use of an unrelated donor • viral infection (eg, cytomegalovirus) • splenectomy • DLI • use of blood as a source of stem cells.

Early Treatment Intervention Is Key: Initial studies reported by Sullivan et al indicated that treatment with corticosteroids alone used late in the course of chronic GVHD resulted in a 23% survival probability at 3 years after transplantation [7] compared to 76% if treatment was administered earlier in the course of the disease [8].

Potential Complications Associated with Steroid-Based Treatment: 
 
• Cataracts • Myopathy  • Headaches • Avascular necrosis • Mood swings 
• Venous fragility • Hypertension • Swelling/edema • Gastritis • Thinning of the skin 
• Hyperglycemia • Increased catabolism • Adrenal suppression • Fever suppression 
• Adipose redistribution • Immune suppression • Osteopenia

 


Resources

PubMed TOPIC Searches
Graft vs Host
| Novel therapies for GvHD | Polymorphisms and GvHD | Approaches  
Donor CD4+CD25 Regulatory T-cells

  1. About GVHD

    Recommended resource:  emedicine
  2. Also see  medicalistes.org | Q&A  fhcrc.org |
     
    Prevention and treatment of acute GVHD medicalistes.org 
    Stages of the disease medicalistes.org 
      
    Treatment of chronic GVHD  medicalistes.org 
    Symptoms and side effects of treatment  medicalistes.org 
  3. What can be done about chronic GVHD - 
    Blood and Marrow Transplantation Reviews 2002  PDF   
     
    "This is a review article looking at a variety of recent published research articles on the subject. Looks at things such as pentostatin in GvHD, extracoproreal photopheresis (ECP), and risk factors." - Scott S.
  4. Morbidity and Mortality of Chronic GVHD After Hematopoietic Stem Cell Transplantation 
    From HLA-Identical Siblings for Patients With Aplastic or Refractory Anemias   www.peds.umn.edu
  5. Support group for GVHD  http://listserv.acor.org/archives/gvhd.html 
 

Treatments

In the News:

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2013: Blood: Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease http://bloodjournal.hematologylibrary.org/content/121/12/2340.full

factors associated with increased risks of treatment failure included high-risk disease at transplantation; high-intensity conditioning with total-body irradiation compared with high-intensity conditioning without total-body irradiation; lower gastrointestinal involvement at second-line treatment; >3 involved sites with chronic GVHD as compared with ≤2 involved sites; severe NIH global score of chronic GVHD compared with mild or moderate NIH global score; and thrombocytopenia, hyperbilirubinemia, and prednisone doses ≥1 mg/kg per day compared with no prednisone immediately before second-line treatment. In multivariate analysis, 3 factors remained statistically significant: (1) high-risk disease at transplantation, (2) lower gastrointestinal involvement at second-line treatment, and (3) severe NIH global score at second-line treatment (Table 3). Thrombocytopenia was dropped early from the model because it correlated with lower gastrointestinal involvement and prednisone dose.
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2010, Case report: Effectiveness and Safety of Tocilizumab, an Anti–Interleukin-6 Receptor Monoclonal Antibody, in a Patient With Refractory GI Graft-Versus-Host Disease jco.ascopubs.org/
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2011, BMT, Therapy of steroid-refractory acute GVHD with CD52 antibody (alemtuzumab) is effective nature.com

Seventeen of 18 patients responded to alemtuzumab, six patients are alive with a median follow-up of 108 weeks. Chronic GVHD was observed frequently. Although pronounced lymphocyte depletion requiring close monitoring for signs of infections seems inevitable for efficacy, alemtuzumab given in moderate doses has a substantial activity not only in intestinal but also in severe acute GVHD of the liver.
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2012 MNT: In Bone Marrow Transplant Patients, Maraviroc Reduces Graft-Vs.-Host Disease

Clinical Trials

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Graft versus Host disease studies 

Treatments for GVHD 

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New approaches for preventing and treating chronic graft-versus-host disease
Stephanie J. Lee ~ From the Department of Medical Oncology, 
Dana-Farber Cancer Institute, Boston, MA.  bloodjournal.org 
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Study shows rituximab effective in treating chronic graft-versus-host disease (2006)  eurekalert.org 
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Background on GVHD (Graft-Versus-Host Disease): 
A Guide for Patients and Families After Stem Cell Transplant  http://bit.ly/DrGiY 

Research News

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NEWS GVHD: Prochymal no better than a placebo in two final trials http://bit.ly/BkDo9 

Osiris said Tuesday preliminary results for two Phase III trials evaluating Prochymal for the treatment of acute graft versus host disease showed no statistical difference between the drug and a placebo in either trial. Osiris said Prochymal did show significant improvements in response rates in difficult-to-treat liver and gastrointestinal graft versus host disease even as it failed to meet its primary endpoint in both trials.
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Outcome report on GVHD: Treatment of steroid-resistant acute GVHD with OKT3 and high-dose steroids results in better disease control and lower incidence of infectious complications when compared to high-dose steroids alone: a randomized multicenter trial by the EBMT Chronic Leukemia Working Party.

Leukemia. 2007 Aug;21(8):1830-3. Epub 2007 May 10. No abstract available. PMID: 17495972
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Protein Level (TNF) Predicts Who Will Develop Graft versus Host Disease After Marrow Transplant   docguide.com
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Prognostic factors of chronic graft-versus-host disease after allogeneic blood stem-cell transplantation.
Am J Hematol. 2005 Apr;78(4):265-74. PMID: 15795914
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Application of natural killer T-cells to posttransplantation immunotherapy. Int J Hematol. 2005 Jan;81(1):1-5. PMID: 15717680
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[1233] Pretreatment with Rituximab Reduces the Incidence of Chronic Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation in Patients with B Cell Lymphoma. Session Type: Poster Session 387-I  ASH 2004
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[1244] Excellent Long-Term Survival of Patients with Steroid-Refractory and Steroid-Dependent Acute Graft-Versus-Host Disease after Extracorporeal Photochemotherapy. Session Type: Poster Session 398-I  ASH 2004  
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Infliximab for the treatment of severe steroid refractory acute graft-versus-host disease in three patients after allogeneic hematopoietic transplantation. Leuk Lymphoma. 2003 Dec;44(12):2095-7. PMID: 14959853 | Related articles 
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Tumor necrosis factor-alpha blockade for the treatment of acute [steroid resistant] GVHD.
Blood. 2004 Aug 1;104(3):649-54. Epub 2004 Apr 06. PMID: 15069017 | Related articles
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Safety and Efficacy of Denileukin Diftitox (Ontak) in Patients with Steroid Refractory Graft-versus-Host Disease (GVHD) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)  bloodjournal
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Drugs (HDAC inhibitors) Limit Deadly Side Effects Of Graft-versus-host Disease Date: 2004-03-01 Source: University Of Michigan Health System  sciencedaily.com
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Novel therapeutics for the treatment of graft-versus-host disease. Expert Opin Investig Drugs. 2002 Sep;11(9):1271-80. Review. PMID: 12225248
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Extracorporeal Photopheresis for Graft-Versus-Host Disease  PDF
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Donor-type CD4+CD25+ Regulatory T Cells Suppress Lethal Acute Graft-Versus-Host Disease after Allogeneic Bone Marrow Transplantation - Full text jem.20020399 | Related abstracts
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Preparative regimens of thymoglobulin beneficial for marrow transplant
patients - Preparative regimen found to reduce risk of acute and chronic GVHD.  bbmt
Safety Information
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Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells vs. bone marrow in allogeneic recipients: long-term follow-up of a randomized trial  bloodjournal, 15_July_2002 
 
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