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

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.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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