Graft vs host disease

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Treatments > Graft versus Host Disease

Last update: 08/10/2013

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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.^{3,4" bloodjournal.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

About GVHD

Recommended resource: emedicine
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
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.
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
Support group for GVHD http://listserv.acor.org/archives/gvhd.html

Treatments

In the News:

	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.
	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/
	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.
	2012 MNT: In Bone Marrow Transplant Patients, Maraviroc Reduces Graft-Vs.-Host Disease

Clinical Trials

Graft versus Host disease studies

Treatments for GVHD

	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
	Study shows rituximab effective in treating chronic graft-versus-host disease (2006) eurekalert.org
	Background on GVHD (Graft-Versus-Host Disease): A Guide for Patients and Families After Stem Cell Transplant http://bit.ly/DrGiY