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Graft vs Host Disease

  

Main  | Allogeneic | Autologous | Cord Blood | Mini | Harvesting Stem Cells | Graft vs Host Disease

Treatments > Bone Marrow & Stem Cell Transplants > Graft vs Host Disease

Last update: 02/17/2008

PubMed TOPIC SEARCH : Donor CD4+CD25 Regulatory T-cells | Approaches | Novel

Resources | Clinical Trials | Treatments | Research News

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].

Resources

TOPIC SEARCHES on GvHD
ASCO.org | JCO.org | Medscape | MSKCC

Clinical Trials on ClinicalTrials.gov for: 
Graft versus Host disease
 

PubMed TOPIC SEARCHES: 
Graft vs Host
| Novel therapies for GvHD | Polymorphisms and GvHD

  1. About GVHD  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 
  2. What can be done about chronic GVHD - Blood and Marrow Transplantation Reviews 2002 
    PDF | PDF-Help  
    "This is a review article looking at a variety of recent published research articles on the subject. It's a PDF file and it's long, so I have the link only for you, but it looks at things such as pentostatin in GvHD, extracoproreal photopheresis (ECP), and risk factors." - Scott S.
  3. Morbidity and Mortality of GVHD After Stem Cell Transplant
    Morbidity and Mortality of Chronic GVHD After Hematopoietic Stem Cell Transplantation 
    From HLA-Identical Siblings for Patients With Aplastic or Refractory Anemias   umn.edu
  4. 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 
  5. Study shows rituximab effective in treating chronic graft-versus-host disease (2006)  eurekalert.org 
  6. Support group for GVHD  http://listserv.acor.org/archives/gvhd.html 

Clinical Trials

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GvHD in ClinicalTrials.gov
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acute GvHD
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chronic GvHD  

Treatments for GVHD (under construction)

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Alternating-day cyclosporine (CsA) and prednisone. 2

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
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Chemotherapy - purine inhibitors - Related PubMed articles
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Investigational: T-cell depleting antibodies - PubMed | clinical trials
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Photopherisis - PDF | clinical trials
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Dor BioPharma's orBec found effective against gastrointestinal GVHD pharmaceutical-business-review
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Kiadis Pharma Announces Successful Completion Of Rhitol(TM) Phase II Clinical Study 
medicalnewstoday

Research News

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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] Petreatment 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)  abstracts2view  December 9, 2003
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Denileukin diftitox (Ontak) for GvHD tops news at Tandem BMT  hemonctoday.com Mar 2004
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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.  hemonctoday.com  03_03
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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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Preparative regimens of thymoglobulin beneficial for marrow transplant patients Preparative regimen found to reduce risk of acute and chronic GVHD.   hemonctoday.com 03_24_03
"Thymoglobulin is a pasteurized anti-thymocyte rabbit immunoglobulin that induces immunosuppression as a result of T-cell depletion and immune modulation. Thymoglobulin is made up of a variety of antibodies that recognize key receptors on T-cells, the cells of a transplant recipient's immune system that recognize and ultimately reject foreign objects such as a transplant. While the exact mechanism is unknown, researchers believe Thymoglobulin antibodies may inactivate and kill these T-cells, thus reversing the rejection process"  sangstat.com
 
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professional medical advice or to replace your relationship with a physician.
For all medical concerns,  you should always consult your doctor. 
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