Graft versus host disease

Acute graft versus host disease (GVHD): staging and grading criteria

Acute GVHD is graded on the extent of involvement (stage) of each of the target organs, namely the skin, gastrointestinal (GI) tract, and liver. Several criteria are commonly used for staging and grading acute GVHD.

Keystone (modified Glucksberg) criteria[83]Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8. http://www.ncbi.nlm.nih.gov/pubmed/7581076?tool=bestpractice.com

Widely used at transplant centers.[83]Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8. http://www.ncbi.nlm.nih.gov/pubmed/7581076?tool=bestpractice.com The skin is staged based on percent of body surface area (BSA) involvement of maculopapular rash. The gastrointestinal tract is staged based on the volume of stool output, and the liver is staged based on degree of bilirubinemia. In children, stool output is measured per kilogram body weight.[84]Jacobsohn DA. Acute graft versus-host disease in children. Bone Marrow Transplant. 2008 Jan;41(2):215-21. http://www.ncbi.nlm.nih.gov/pubmed/17934526?tool=bestpractice.com

An overall grade is assigned based on the individual stages of the organs involved, which reflects the actual extent of GVHD. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate disease, grade III as severe disease, and grade IV as very severe and life-threatening disease.

MAGIC criteria[85]Harris AC, Young R, Devine S, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2016 Jan;22(1):4-10. https://www.astctjournal.org/article/S1083-8791(15)00602-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/26386318?tool=bestpractice.com

International expert consensus criteria developed to standardize the inclusion of acute GVHD symptoms of the GI tract as part of clinical staging and grading.

Staging is based on clinical manifestations of the skin, GI tract (upper and lower), and liver, with an overall grade assigned based on the most severe target organ involvement.

Acute GVHD stage

• Stage 0

  • Skin (active erythema only): no active (erythematous) GVHD rash

  • Liver (bilirubin): <2 mg/dL

  • Upper GI: no or intermittent nausea, vomiting, or anorexia

  • Lower GI (stool output/day): adults <500 mL/day or <3 episodes/days; children <10 mL/kg/day or <4 episodes/day

• Stage 1

  • Skin (active erythema only): maculopapular rash <25% BSA

  • Liver (bilirubin): 2-3 mg/dL

  • Upper GI: persistent nausea, vomiting or anorexia

  • Lower GI (stool output/day): adults: 500-999 mL/day or 3-4 episodes/day; children:10.0 to 19.9 mL/kg/day or 4-6 episodes/day

• Stage 2

  • Skin (active erythema only): maculopapular rash 25% to 50% BSA

  • Liver (bilirubin): 3.1 to 6.0 mg/dL

  • Lower GI (stool output/day): adults: 1000-1500 mL/day or 5-7 episodes/day; children: 20-30 mL/kg/day or 7-10 episodes/day

• Stage 3

  • Skin (active erythema only): maculopapular rash >50% BSA

  • Liver (bilirubin): 6.1 to 15.0 mg/dL

  • Lower GI (stool output/day): adults: >1500 mL/day or >7 episodes/day; children: >30 mL/kg/day or >10 episodes/day

• Stage 4

  • Skin (active erythema only): generalized erythroderma (>50% BSA) plus bullous formation and desquamation >5% BSA

  • Liver (bilirubin): >15 mg/dL

  • Lower GI (stool output/day): severe abdominal pain with or without ileus or grossly bloody stool (regardless of stool volume)

Acute GVHD grade

• Grade 0

  • No stage 1-4 of any organ

• Grade I

  • Stage 1-2 skin without liver, upper GI, or lower GI involvement

• Grade II

  • Stage 3 rash and/or stage 1 liver and/or stage 1 upper GI and/or stage 1 lower GI

• Grade III

  • Stage 2-3 liver and/or stage 2-3 lower GI, with stage 0-3 skin and/or stage 0-1 upper GI

• Grade IV

  • Stage 4 skin, liver, or lower GI involvement, with stage 0-1 upper GI

Minnesota refined acute GVHD risk score

​​Stratifies patients as either standard risk or high risk depending on stage and grade.[86]MacMillan ML, DeFor TE, Weisdorf DJ. What predicts high risk acute graft-versus-host disease (GVHD) at onset? Identification of those at highest risk by a novel acute GVHD risk score. Br J Haematol. 2012 Jun;157(6):732-41. https://pmc.ncbi.nlm.nih.gov/articles/PMC3654854 http://www.ncbi.nlm.nih.gov/pubmed/22486355?tool=bestpractice.com [87]MacMillan ML, DeFor TE, Holtan SG, et al. Validation of Minnesota acute graft-versus-host disease risk score. Haematologica. 2020;105(2):519-24. https://pmc.ncbi.nlm.nih.gov/articles/PMC7012472 http://www.ncbi.nlm.nih.gov/pubmed/31320554?tool=bestpractice.com ​​ [ The Minnesota Refined Acute GvHD Risk Score Opens in new window ] ​

Chronic GVHD: staging and grading criteria

The National Institutes of Health (NIH) working group scoring system for chronic GVHD[1]Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329079 http://www.ncbi.nlm.nih.gov/pubmed/25529383?tool=bestpractice.com National Institutes of Health: organ scoring of chronic GVHD Opens in new window

Can be used to assess disease severity and prognosis based on specific signs, degree of organ involvement (mild, moderate, severe), and laboratory data.

The NIH working group scoring system recommends:

• at least one diagnostic manifestation (e.g., oral or vaginal lichenoid findings, skin dyspigmentation, bronchiolitis obliterans), or

• one distinctive manifestation (e.g., ocular sicca, depigmentation, papulosquamous plaques) plus a pertinent biopsy, laboratory, or other test for the diagnosis of chronic GVHD.