Graft-versus-host disease classification

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Graft-versus-host disease


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2]


Classification can be related to time-of-onset or to disease severity. Time-of-onset classification divides GvHD into acute or chronic, based on the key time point of 100 days. Severity classification divides GvHD into stages and grades, as defined by the International Bone Marrow Transplant Registry (IBMTR). The ultimate grade of GvHD is determined by the stages of the individual organs affected. Grade 1 GvHD, for example, is characterized by skin involvement but without liver or GI involvement.


  • Clinically, graft-versus-host-disease is divided into acute and chronic forms.
    • The acute or fulminant form of the disease (aGVHD) is normally observed within the first 100 days post-transplant[1], and is a major challenge to transplants owing to associated morbidity and mortality[2].
    • The chronic form of graft-versus-host-disease (cGVHD) normally occurs after 100 days. The appearance of moderate to severe cases of cGvHD adversely influences long-term survival [3].
    • The overlap syndrome includes features of both acute and chronic GvHD. This is less commonly encountered.[4]
  • This distinction is not arbitrary: acute and chronic GvHD appear to involve different immune cell subsets, different cytokine profiles, somewhat different host targets, and respond differently to treatment.




The conglomeration of staging gives rise to a grade. The grading system is as follows:

  • Grade 1: skin stage 1-2 with no liver or GI involvement
  • Grade 2: skin stage 3 or liver stage 1 or GI stage 1
  • Grade 3: skin with any stage or liver stage 2-3 or GI stage 2-4
  • Grade 4: skin stage 4 or liver stage 4 or GI with any stage

Transfusion-associated GVHD

  • This type of GvHD is associated with transfusion of un-irradiated blood to immunocompromised recipients. It can also occur in situations where the blood donor is homozygous and the recipient is heterozygous for an HLA haplotype. It is associated with higher mortality (80-90%) due to involvement of bone marrow lymphoid tissue, however the clinical manifestations are similar to GVHD resulting from bone marrow transplantation. Transfusion-associated GvHD is rare in modern medicine. It is almost entirely preventable by controlled irradiation of blood products to inactivate the white blood cells (including lymphocytes) within.


  1. Graft versus Host Disease, from the National Marrow Donor Program
  2. Goker H, Haznedaroglu IC, Chao NJ (2001). "Acute graft-vs-host disease: pathobiology and management". Exp. Hematol. 29 (3): 259–77. PMID 11274753.
  3. Lee SJ, Vogelsang G, Flowers ME (2003). "Chronic graft-versus-host disease". Biol. Blood Marrow Transplant. 9 (4): 215–33. doi:10.1053/bbmt.2003.50026. PMID 12720215.
  4. Socié G, Ritz J (2014). "Current issues in chronic graft-versus-host disease". Blood. 124 (3): 374–84. doi:10.1182/blood-2014-01-514752. PMC 4102710. PMID 24914139.
  5. Qian L, Wu Z, Shen J (2013). "Advances in the treatment of acute graft-versus-host disease". J Cell Mol Med. 17 (8): 966–75. doi:10.1111/jcmm.12093. PMC 3780546. PMID 23802653.