Manifestations of Chronic GVHD in Other Organ Systems

  • Cecilia C. S. YeungEmail author
  • Howard M. Shulman


Following HSCT, donor T cells reacting to differences in a recipient’s genetically determined histocompatibility antigens cause acute GVHD (aGVHD). The immunologic targets includes the thymus resulting in the generation of autoreactive T cells, which later lead to autoimmune-like manifestations in chronic GVHD (cGVHD). Well-established manifestations of cGVHD include dermal sclerosis, sicca syndrome, and bronchiolitisobliterans syndrome, as well as eosinophilia and thrombocytopenia. This chapter describes several of the infrequent or rare clinical-pathological autoimmune-like findings associated with cGVHD such as polymyositis, myasthenia gravis, and serositis. Much less common, poorly understood, or controversial are coronary arteritis, retroperitoneal fibrosis associated with elevated IgG4, and lymphocytic cerebritis.


Chronic GVHD Autoimmunity Thymic injury Polymyositis Myasthenia gravis Serositis Coronary arteritis Retroperitoneal fibrosis Central nervous system manifestation of GVHD Lymphocytic cerebritis Bone marrow involvement with GVHD 


  1. 1.
    Krenger W, Hollander GA. The thymus in GVHD pathophysiology. Best Pract Res Clin Haematol. 2008;21(2):119–28.PubMedCrossRefGoogle Scholar
  2. 2.
    Zeiser R, Blazar BR. Acute graft-versus-host disease – biologic process, prevention, and therapy. N Engl J Med. 2017;377(22):2167–79.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Tsutsumi Y, Kamiishi T, Kikuchi R, Ito S, Matsuoka S, Teshima T. Myasthenia gravis after allogeneic bone marrow transplantation: a case report and literature review. Hematol Oncol Stem Cell Ther. 2017;S1658-3876(17)30052–3.Google Scholar
  4. 4.
    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;21(3):389–401 e381.Google Scholar
  5. 5.
    Fukatsu M, Murakami T, Ohkawara H, et al. A possible role of low regulatory T cells in anti-acetylcholine receptor antibody positive myasthenia gravis after bone marrow transplantation. BMC Neurol. 2017;17(1):93.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Horowitz MM, Rowlings PA. An update from the International Bone Marrow Transplant Registry and the Autologous Blood and Marrow Transplant Registry on current activity in hematopoietic stem cell transplantation. Curr Opin Hematol. 1997;4(6):395–400.PubMedCrossRefGoogle Scholar
  7. 7.
    Mackey JR, Desai S, Larratt L, Cwik V, Nabholtz JM. Myasthenia gravis in association with allogeneic bone marrow transplantation: clinical observations, therapeutic implications and review of literature. Bone Marrow Transplant. 1997;19(9):939–42.PubMedCrossRefGoogle Scholar
  8. 8.
    Kotani A, Takahashi A, Koga H, et al. Myasthenia gravis after allogeneic bone marrow transplantation treated with mycophenolate mofetil monitored by peripheral blood OX40+ CD4+ T cells. Eur J Haematol. 2002;69(5–6):318–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Shimoda K, Gondo H, Harada M, et al. Myasthenia gravis after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1994;14(1):155–6.PubMedGoogle Scholar
  10. 10.
    Sauter A, Bethge W, Vogel U, Horger M. Cervical fascial and muscular involvement in chronic GVHD after Allo-SCT and radiation therapy. Bone Marrow Transplant. 2009;44(7):451–2.PubMedCrossRefGoogle Scholar
  11. 11.
    Morimoto Y, Oka S, Tashima M, Hamahata K, Nohgawa M. Chronic GVHD complicated with polymyositis and cardiomyopathy after myeloablative hematopoietic stem cell transplantation. Rinsho Ketsueki. 2015;56(5):485–90.PubMedGoogle Scholar
  12. 12.
    Oda K, Nakaseko C, Ozawa S, et al. Fasciitis and myositis: an analysis of muscle-related complications caused by chronic GVHD after allo-SCT. Bone Marrow Transplant. 2009;43(2):159–67.PubMedCrossRefGoogle Scholar
  13. 13.
    Sakamoto K, Imamura T, Niwa F, et al. Dermatomyositis developed in a recipient of allogeneic BMT; the differentiation of chronic GVHD and autoimmune disease. Bone Marrow Transplant. 2012;47(4):603–4.PubMedCrossRefGoogle Scholar
  14. 14.
    Rackley C, Schultz KR, Goldman FD, et al. Cardiac manifestations of graft-versus-host disease. Biol Blood Marrow Transplant. 2005;11(10):773–80.PubMedCrossRefGoogle Scholar
  15. 15.
    Gilman AL, Kooy NW, Atkins DL, et al. Complete heart block in association with graft-versus-host disease. Bone Marrow Transplant. 1998;21(1):85–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Chan KW, Taylor GP, Shepherd JD, Shepherd WE. Coronary artery disease following bone marrow transplantation. Bone Marrow Transplant. 1989;4(3):327–30.PubMedGoogle Scholar
  17. 17.
    Prevost D, Taylor G, Sanatani S, Schultz KR. Coronary vessel involvement by chronic graft-versus-host disease presenting as sudden cardiac death. Bone Marrow Transplant. 2004;34(7):655–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Cereda M, Trocino G, Pogliani EM, Schiavina R. A case of cardiac localization of graft-versus-host disease after allogenic bone marrow transplantation. Ital Heart J. 2003;4(1):60–3.PubMedGoogle Scholar
  19. 19.
    Medinger M, Tichelli A, Bucher C, et al. GVHD after allogeneic haematopoietic SCT for AML: angiogenesis, vascular endothelial growth factor and VEGF receptor expression in the BM. Bone Marrow Transplant. 2013;48(5):715–21.PubMedCrossRefGoogle Scholar
  20. 20.
    Mir E, Palomo M, Rovira M, et al. Endothelial damage is aggravated in acute GvHD and could predict its development. Bone Marrow Transplant. 2017;52(9):1317–25.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Polchlopek Blasiak K, Simonetta F, Vargas MI, Chalandon Y. Central nervous system graft-versus-host disease (CNS-GvHD) after allogeneic haematopoietic stem cell transplantation. BMJ Case Rep. 2018;2018:bcr-2017–221840.Google Scholar
  22. 22.
    Kaliyaperumal S, Watkins B, Sharma P, et al. CD8-predominant T-cell CNS infiltration accompanies GVHD in primates and is improved with immunoprophylaxis. Blood. 2014;123(12):1967–9.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Shulman HM, Sullivan KM, Weiden PL, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69(2):204–17.PubMedCrossRefGoogle Scholar
  24. 24.
    Seber A, Khan SP, Kersey JH. Unexplained effusions: association with allogeneic bone marrow transplantation and acute or chronic graft-versus-host disease. Bone Marrow Transplant. 1996;17(2):207–11.PubMedGoogle Scholar
  25. 25.
    J T Leonard, L F Newell, G Meyers, B Hayes-Lattin, J Gajewski, S Heitner, S Nonas, B Allen, A Stentz, R Frires, R T Maziarz, S G Holtan, (2015) Chronic GvHD-associated serositis and pericarditis. Bone Marrow Transplantation 50(8):1098–104PubMedCrossRefGoogle Scholar
  26. 26.
    M Gyger, A Rosenberg, A Shamy, A Hercz, S Caplan, I A Sebag, M L Brisson, D C Roy, (2005) Vascular leak syndrome and serositis as an unusual manifestation of chronic graft-versus-host disease in nonmyeloablative transplants. Bone Marrow Transplantation 35(2):201–3CrossRefGoogle Scholar
  27. 27.
    Dicke C, Kertesz A, Henke RP, et al. Retroperitoneal fibrosis as manifestation of chronic GVHD after allogeneic hematopoietic SCT. Bone Marrow Transplant. 2013;48(3):467–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Nanda A, Rizzo JD, Vogelsang GB. A case of retroperitoneal fibrosis in a patient following HSCT. Bone Marrow Transplant. 2005;35(11):1125–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Lian L, Wang C, Tian JL. IgG4-related retroperitoneal fibrosis: a newly characterized disease. Int J Rheum Dis. 2016;19(11):1049–55.PubMedCrossRefGoogle Scholar
  30. 30.
    Ahmad I, Labbé A-C, Chagnon M, Busque L, Cohen S, Kiss T, Lachance S, Roy D-C, Sauvageau G, Roy J. Incidence and prognostic value of eosinophilia in chronic graft-versus-host disease after nonmyeloablative hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011;17(11):1673–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Leonard JT, Newell LF, Meyers G, Hayes-Lattin B, Gajewski J, Heitner S, Nonas S, Allen B, Stentz A, Frires R, Maziarz RT, Holtan SG. Chronic GvHD-associated serositis and pericarditis. Bone Marrow Transplant. 2015;50(8):1098–104.PubMedCrossRefGoogle Scholar
  32. 32.
    Gyger M, Rosenberg A, Shamy A, Hercz A, Caplan S, Sebag IA, Brisson ML, Roy DC. Vascular leak syndrome and serositis as an unusual manifestation of chronic graft-versus-host disease in nonmyeloablative transplants. Bone Marrow Transplant. 2005;35(2):201–3.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Department of PathologyUniversity of Washington School of MedicineSeattleUSA
  3. 3.Pathology SectionSeattle Cancer Care AllianceSeattleUSA

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