Abstract
A total of 61 patients with haematological malignancies were randomised either to allogeneic transplantation with blood stem cells (BSC) or bone marrow (BM), of whom 37 patients gave their consent to participate in a skin biopsy trial. Skin biopsies were performed before and after transplantation. The main objective was to assess whether biopsies of normal and affected skin from patients allografted with BSC showed a different histopathological and immunohistochemical pattern as compared to biopsies taken from patients allografted with BM. In addition, we wished to clarify whether sequential skin biopsies could be of prognostic value with regard to graft-versus-host disease (GVHD). Biopsies from normal or affected skin in BSC allografted did not disclose a different pattern as compared to BM transplants. Biopsies taken before the outbreak of acute and chronic GVHD showed no substantial differences between the groups. Irrespective of the type of allograft, the immunohistochemical picture of affected skin consistent with acute GVHD was dominated by a significantly higher number of T-lymphocytes (CD8+). Biopsies from normal skin before the outbreak of GVHD had no predictive value with regard to the development of acute or chronic GVHD. Immunohistochemistry is of supplementary help in distinguishing changes caused by cytotoxic agents from those caused by acute GVHD.
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References
Ringdén O, Deeg HJ . Clinical spectrum of graft-versus-host disease. In: Ferrara JLM, Deeg HJ, Burakoff SJ (eds.). Graft-Versus-Host Disease. Marcel Dekker: New York, 1997; pp 525–559.
Weaver CH, Longin K, Buckner CD, Bensinger W . Lymphocyte content in peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor. Bone Marrow Transplant 1994; 13: 411–415.
Körbling M, Huh YO, Durett A et al. Allogeneic blood stem cell transplantation: peripheralization and yield of donor derived primitive hematopoietic progenitor cells (CD34+ Thy-1dim) and lymphoid subsets, and possible predictors of engraftment and GVHD. Blood 1995; 86: 2842–2848.
Vigorito AC, Azevedo WM, Marques JF et al. A randomised, prospective comparison of allogeneic bone marrow and peripheral blood progenitor cell transplantation in the treatment of haematological malignancies. Bone Marrow Transplant 1998; 22: 1145–1151.
Blaise D, Kuentz M, Fortanier C et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukaemia: a report from the Société Française de Greffe de Moelle. J Clin Oncol 2000; 18: 537–546.
Powles R, Mehta J, Kulkarni S et al. Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial. Lancet 2000; 355: 1231–1237.
Heldal D, Tjønnfjord G, Brinch L et al. A randomised study of allogeneic transplantation with stem cells from blood or bone marrow. Bone Marrow Transplant 2000; 25: 1129–1136.
Couban S, Simpson DR, Barnett MJ et al. A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies. Blood 2002; 100: 1525–1531.
Bensinger WI, Martin PJ, Storer B et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 3: 175–181.
Schmitz N, Beksac M, Hasenclever D et al. Transplantation of mobilized peripheral blood cells to HLA-identical siblings with standard-risk leukaemia. Blood 2002; 100: 761–767.
Mohty M, Kuentz M, Michallet M et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomized study. Blood 2002; 100: 3128–3134.
Heldal D, Brinch L, Tjønnfjord G et al. Fewer relapses and increased chronic GVHD in patients transplanted with blood stem cells: a 5-year follow-up in a single centre study. Bone Marrow Transplant 2003; 32: 257–264.
Hepburn NC, McLaren KM, Turner ML, Beveridge GW . The role of skin biopsies in bone marrow recipients. Q J Med 1993; 86: 715–717.
Esteban JM, Somlo G . Skin biopsy in allogeneic and autologous bone marrow transplant patients: a histologic and immunohistochemical study and review of the literature. Mod Pathol 1995; 8: 59–64.
Diamond DJ, Chang KL, Jenkins KA, Forman SJ . Immunohistochemical analysis of T cell phenotypes in patients with graft-versus-host disease following allogeneic bone marrow transplantation. Transplantation 1995; 10: 1436–1444.
Kohler S, Hendrickson MR, Chao NJ, Smoller BR . Value of skin biopsies in assessing prognosis and progression of acute graft-versus-host disease. Am J Surg Pathol 1997; 21: 988–996.
Dickinson AM, Sviland L, Wang XN . Predicting graft-versus-host disease in HLA-identical bone marrow transplant: a comparison of T-cell frequency analysis and a human skin explant model. Transplantation 1998; 66: 857–863.
Dickinson A, Hromadnikova I, Sviland L . Use of a skin explant model for predicting GVHD in HLA-matched bone marrow transplants – effect of GVHD prophylaxis. Bone Marrow Transplant 1999; 24: 857–863.
Sviland L, Dickinson AM . A human skin explant model for predicting graft-versus-host disease following bone marrow transplantation. J Clin Pathol 1999; 52: 910–913.
Sviland L . The pathology of bone marrow transplantation. Curr Diagn Pathol 2000; 6: 242–250.
Glucksberg H, Storb R, Fefer A et al. Clinical manifestation of graft-versus-host disease in human recipients of marrow from HLA matched sibling donors. Transplantation 1974; 18: 295–304.
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: 204–217.
Lerner KG, Kao GF, Storb CD . Histopathology of graft-versus-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors. Transplant Proc 1974; 6: 367–371.
Leskinen R, Taskinen E, Volin L et al. Immunohistology of skin and rectum biopsies in bone marrow transplant recipients. APMIS 1992; 100: 1115–1122.
Favre A, Cerri A, Bacigalupo A, Lanino E et al. Immuno-histochemical study of skin lesions in acute and chronic graft versus host disease following bone marrow transplantation. Am J Surg Pathol 1997; 21: 23–34.
Yamada H, Chihara J, Hamada K et al. Immunohistology of skin and oral biopsies in graft-versus-host disease after bone marrow transplantation and cytokine therapy. J Allergy Clin Immunol 1997; 100: 73–76.
Sviland L, Pearson ADJ, Eastham EJ et al. Class II antigen expression by keratincytes – an early feature of graft-versus-host disease. Transplantation 1988; 46: 402–406.
Loughran TP, Sullivan K, Morton T et al. Value of day 100 screening studies for predicting the development of chronic graft-versus-host disease after allogeneic bone marrow transplantation. Blood 1990; 76: 228–234.
Acknowledgements
This study was supported by Bergliot and Sigurd Skaugen's ‘Fond til bekjempelse av kreft’. We also thank Hilde Beate Vik, the nurses, the medical staff and the administrative personnel at The Section of Haematology, Medical Department, Rikshospitalet University Hospital, Oslo for their excellent cooperation and patient care, and above all thanks to Marit Hatlestad Nilsen, The Gade Institute, Haukeland University Hospital, Bergen, who deserves our deepest gratitude for her meticulous preparation of the immunohistochemical specimens.
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Heldal, D., Brinch, L., Evensen, S. et al. Skin biopsies for early diagnosis and prognosis of graft-versus-host disease in recipients of allogeneic stem cells from blood or bone marrow. Bone Marrow Transplant 34, 345–350 (2004). https://doi.org/10.1038/sj.bmt.1704568
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DOI: https://doi.org/10.1038/sj.bmt.1704568
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