Graft-versus-host disease (GVHD)

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OnSurg thanks collaborative partner Dr Anubhav Mittal at for making this valuable content available. Dr Mittal tweets at @anubhavnz.


Despite the initial use of systemic corticosteroids for treatment of grade II-IV acute GVHD, typically in combination with a calcineurin inhibitor, complete response (CR) rates have remained approximately 25% to 40%. Unfortunately, in some cases, withdrawal of corticosteroid therapy can lead to a flare of acute GVHD and/or evolve into chronic GVHD. The exact rate of flares is unpredictable, but is higher in mismatched or unrelated donor haematopoietic cell transplantations (HCTs).


The number of allogeneic haematopoietic cell transplantations (HCTs) continues to increase, with more than 20,000 allogeneic transplantations performed annually worldwide. In 2006, the estimated number of allogeneic HCTs reported in the US to the Center for International Blood and Marrow Transplant Research (CIBMTR) was 6100 (3800 related donors and 2300 unrelated donors).


Graft-versus-host disease (GVHD) is a major complication following allogeneic haematopoietic cell transplantation (HCT) and occurs when donor T cells respond to histoincompatible antigens on the host tissues.
Acute GVHD classically develops within the first 100 days of transplant or can occur beyond 100 days post-transplant with persistent, recurrent, or late-onset symptoms. The principle target organs include the skin, liver, and GI tract.
Chronic GVHD may emerge from acute disease (progressive type), develop following a period of resolution from acute disease (quiescent or interrupted type), or occur de novo. The manifestations can be variable, and are often similar to those seen in autoimmune diseases.
Overlap syndrome is characterised by clinical features that resemble a combination of both acute and chronic GVHD.

History and Exam

allogeneic haematopoietic cell transplantation (HCT) recipient
unrelated donor
multiparous female donor
diffuse maculopapular rash with fever
nausea, abdominal pain, and profuse diarrhoea

Investigations / Tests

- serum electrolytes
- liver functions tests
- urinalysis
- urine culture
- blood culture
- stool culture
- viral polymerase chain reaction (PCR)

Case History

A 50-year-old man with a history of Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) receives a HLA-matched unrelated donor (MUD) haematopoietic cell transplantation (HCT). On day 16 post-transplant, the patient develops fever and diffuse maculopapular rash affecting >50% of his body surface area. By day 23 post-transplant, the patient starts developing nausea, abdominal pain, and profuse diarrhoea. On day 35, the patient begins showing signs of jaundice and hepatomegaly on physical examination.


Acute graft-versus-host disease (GVHD):

Risk factors for the development of acute GVHD include HLA disparity, increasing age of the recipient, donor and recipient gender disparity, type and status of underlying disease, transplant conditioning regimen intensity, ABO compatibility, performance score, white/black race, CMV serostatus, and doses of prophylactic immunosuppression medications.


Acute graft-versus-host disease (GVHD):

The pathophysiology of acute GVHD is complex, but can be conceptualised in 3 sequential steps or phases:

Activation of the antigen presenting cells (APCs)

Donor T cell activation, proliferation, differentiation, and migration

Target tissue destruction.

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