Acute Graft Versus Host Disease
Reviewed and revised 29 August 2014
OVERVIEW
- major complication of allogeneic haematopoietic stem cell transplantation
- pathophysiology = antigens on the host cells are attacked by the donated T cells
- About 35%–50% of haematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD
- About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD
DIFFERENTIAL
Tissue biopsy is to helps differentiate from other diagnoses which may mimic GVHD
- neutropenic sepsis
- line sepsis
- drug reactions (SJS)
- mucositis
- skin breakdown
- enteritis (bacterial or viral, e.g. CMV colitis)
- veno-occlusive disease
CLINICAL FEATURES
Trifecta of
- skin — rash
- liver — jaundice, hepatitis
- Gastrointestinal — diarrhoea, abdominal pain, mucositis
Other post-transplant complications may be related to, or actually be a manifestation of, GVHD:
- e.g. non-infectious pulmonary infiltrates upon engraftment (outcome is generally poor)
STAGING AND GRADING
- Acute GVHD is staged and graded (grade 0-IV) by the number and extent of organ involvement
INVESTIGATIONS
- FBC: neutrophils and bone marrow function
- coagulopathy:
- U+E: electrolytes abnormalities associated with diarrhoea
- renal function
- liver function
- microbiology: stool sample, blood cultures, sputum, lines, urine
- CXR: even if no signs
- skin biopsy: lymphocytic infiltration with basilar vacuolization in aGVHD
- rectal biopsy: necrosis, mucosal ulcerations, crypt dropout (relatively specific in aGVHD)
- CT abdomen: luminal dilation with thickening of small bowel wall (“ribbon sign”), air fluid levels suggestive of an ileus in aGVHD
MANAGEMENT
Supportive
- balanced crystalloid
- product resuscitation (RBC must be leucocyte depleted and irradiated)
- electrolyte replacement
- G-CSF: improves neutropenia but no change in mortality
- broad spectrum antimicrobials: antibiotics, antifungals
- antimicrobial prophylaxis: fluconazole, cotrimoxazole, acyclovir
- diarrhoea: antimotility agents, TPN, bowel rest
- if it is recurrent enteric infection: IVIG (controversial)
Specific
About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line) immunosuppressive therapy for which there is currently no standard-of-care.
- systemic corticosteroids: methylprednisolone 2mg/kg/day
- calcineurin antagonists: cyclosporin, tacrolimus
- anti-thymocyte globulin
- monoclonal antibody: diclizumab
- MTOR: sirolimus
- methotrexate
- PUVA
- thalidomide
- phototherapy: extracorporeal photophoresis
- TNF receptor alpha inhibitor: etanercept
- mesenchymal stem cells
PROGNOSIS
- about 50% survival overall at 1 year following intensive steroid therapy
- about 50% develop chronic GVHD
- prognosis varies with grade: Grade I-II ~80% long-term survival, Grade IV ~5% long-term survival
References and Links
LITFL
- CCC — Chronic GVHD
Journal Articles and Textbooks
- Dignan FL, Clark A, Amrolia P, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Hadzic N, Shaw BE, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of acute graft-versus-host disease. Br J Haematol. 2012 Jul;158(1):30-45. PMID: 22533831.
- Jacobsohn DA, Vogelsang GB. Acute graft versus host disease. Orphanet J Rare Dis. 2007 Sep 4;2:35. PMC2018687.
- Socié G, Blazar BR. Acute graft-versus-host disease: from the bench to the bedside. Blood. 2009 Nov 12;114(20):4327-36. PMC2777122.
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
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