What is graft-versus host disease (GVHD)?
Graft-versus host disease
(GVHD) is a condition that may be seen in patients who have undergone a bone
marrow or stem cell transplant (stem cells are undifferentiated cells that can
form specialized cells). In the absence
of a complete match, the cells of transplanted tissue may attack the
recipient's cells leading to a GVHD.
GVHD may be acute or chronic
. Acute GVHD usually occurs within 3 month of
transplantation. Symptoms include pain in abdomen, diarrhea, vomiting, fever,
jaundice, skin rash and weight loss. Chronic GVHD appears after 3 months.
Symptoms include hair loss, lung, digestive tract and liver disorders, and skin
thickening and rash. A patient with GVHD is more prone to infections.
Current treatment includes corticosteroids and other drugs that
What are regulatory and conventional T cells?
Regulatory T cells are cells of the immune system. They play an
important role in suppressing immunity and this prevents GVHD
. On the other hand, the
conventional T cells promote immunity and contribute to GVHD. T cell
dysfunction has been observed in graft-versus-host disease.
The presence of
interleukin-2 (IL-2), a signaling molecule, is required for the growth,
survival and activity of the regulatory as well as conventional T cells.
Efficacy of IL-2 in chronic GVHD:
In a recently published
study, 29 patients with chronic GVHD and not responding to corticosteroids were
administered a low dose of IL-2 as a subcutaneous injection (injected just
below the skin) daily for a total duration of 8 weeks. Patients who showed a
good response to the drug could continue taking it after a 4-week gap.
Among the 23 patients who
were evaluated for response to IL-2, the
total number of T regulatory cells was increased in all the patients
a maximum level at 4 weeks. The level of the conventional T cells was not
affected, thus improving the ratio
between T regulatory cells and conventional T cells by nearly 5 times
improvement in symptoms was observed in around half the patients.
The response was maintained
over a long period, allowing reduction of and, in some cases, discontinuation
of the corticosteroid dose. Reappearance of the blood cancer or progression of
GVHD did not occur in any patient. Side effects noted during the study which
could have been due to IL-2 included fever, malaise and fatigue, kidney
dysfunction and reduced platelet count.
Thus, a daily low dose of IL-2 could benefit patients with GVHD,
especially those unresponsive to corticosteroids
Koreth, et al; N Engl J Med 2011; 365:2055-2066