Graft-versus-host disease natural history, complications and prognosis
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GvHD carries a high morbidity if not appropriately treated, and its natural history can result in organ failure and eventually death. Complications of GvHD include infection, organ damage and, in rare cases, squamous cell carcinoma or other immunosuppression-associated hematolymphoid malignancies. Poor prognostic factors include thrombocytopenia, severe jaundice, older age, >1 liter of diarrhea per day, hypoalbuminemia, and gastrointestinal ulceration. Multiple prognostic tools have been developed, including Johns Hopkins Hospital classification, Center for International Blood and Marrow Transplant Research classification, and the NIH consensus classification.
The natural history of GvHD begins with a stem cell transplant and immunological interactions between donor cells and recipient tissue. Within a short period of time, even within a few days, a clinically significant immunologic response occurs. The natural course of the disease progresses to organ dysfunction in the skin, liver, and GI tract. This dysfunction can last for many weeks and even longer if left untreated. If treated appropriately with immunosuppression, the natural history of GvHD can be hampered, with inhibition of ongoing organ damage. If left untreated, worsening skin, liver, GI, and pulmonary manifestations will inevitably occur as the donor immune cells destroy host tissue. This can lead to:
- Skin breakdown with subsequent infections and sepsis
- Worsening GI dysfunction including high-volume diarrhea and dehydration, as well as sepsis from breakdown of intestinal mucosa
- Respiratory failure if there is pneumonitis
The natural history of GvHD can last for years, with a relapsing and remitting course. Different patients have different manifestations of the disease, and the natural history is thus variable. If patients develop steroid-refractory GvHD, the natural history tends to take an unfavorable course, with high morbidity and mortality. In this case, alternative immunosuppressive medications can be tried. However, the success rate for treatment of steroid-refractory GvHD is low, and the natural history of the disease results in death within a relatively short time.
- Infections: A major complication of GvHD is the resulting immunosuppression that occurs after treatment. Treatment of GvHD focuses on abrogating the abnormal immune activation, and high dose steroids are typically administered. Late fungal infections and Pneumocystis carinii are common in patients who develop GvHD and receive treatment with immunosuppressive agents.
- Non-malignant late complications: These include ophthalmic, skeletal, joint, cardiovascular impairment.
- Malignant complications: These include squamous cell carcinoma of the head and neck (due to HPV infection), squamous cell carcinoma of the skin, and other immunosuppression-associated malignancy like hematolymphoid malignancies.
A few different prognostic classifications have been developed for GvHD.
- Johns Hopkins Hospital
- Center for International Blood and Marrow Transplant Research
- NIH consensus classification: This classification proposes a global chronic severity score and includes the degree to which different organs are involved.
Prognostic factors include:
The risk of mortality is based upon certain clinical features:
- Early satiety
- Stable albumin
- Less than 1 liter per day of diarrhea
- No other features found in the high or very high risk categories below
- Young age
- Upper GI symptoms
- Jaundice of mild severity
- 1 liter per day of diarrhea
- Extensive skin rash
- Decline in albumin by more than 0.5 g/dl
Very high risk:
- Severe jaundice
- Older age
- Greater than 1 liter per day of diarrhea
- Hypoalbuminemia with albumin level than 1.6 g/dl
- GI ulceration
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- 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.