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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
.gif) |
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 AntiInterleukin-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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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
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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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PubMed
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