Abstract
Colonoscopic evaluation of mucosal tissues after allogeneic hematopoietic stem cell transplantation (HSCT) is very useful in evaluating pathogenesis and diagnosis of intestinal graft-versus-host disease (GVHD). However, information on the timing and sites of biopsies and the immunohistological evaluation of mucosal tissues for diagnosing intestinal GVHD, especially following reduced-intensity (RIC) regimens, remains very limited. A total of 33 patients with histologically proven GVHD after allogeneic HSCT with RIC (n = 23) and myeloablative conditioning (MAC, n = 10) regimens were enrolled in the present study. Colonoscopy was performed due to gastrointestinal symptoms, especially diarrhea and anorexia. Sites of biopsies with the worst histopathological grading were the terminal ileum in 67 % of patients. In the RIC group, the onset of diarrhea prior to colonoscopy examination was later (median: RIC, 57 vs. MAC, 27 days) and the number of patients who developed abdominal pain tended to be higher (RIC, 70 % vs. MAC, 30 %). A lower number of CD4+ cells and a higher ratio of Foxp3+ cells to CD4+ cells were detected in the involved lesions of intestinal GVHD following RIC. These differences in the RIC and MAC groups suggest that regimen-specific therapeutic strategies are required for diagnosing intestinal GVHD.
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References
Shlomchik WD, Couzens MS, Tang CB, McNiff J, Robert ME, Liu J, et al. Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science. 1999;285:412–5.
Zeng D, Lewis D, Dejbakhsh-Jones S, Lan F, Garcia-Ojeda M, Sibley R, et al. Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease. J Exp Med. 1999;189:1073–81.
Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–100.
Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, et al. CD4+ CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9:1144–50.
Passweg JR, Stern M, Koehl U, Uharek L, Tichelli A. Use of natural killer cells in hematopoietic stem cell transplantation. Bone Marrow Transpl. 2005;35:637–43.
Rezvani K, Mielke S, Ahmadzadeh M, Kilical Y, Savani BN, Zeilah J, et al. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood. 2006;108:1291–7.
Hill GR, Crawford JM, Cooke KR, Brinson YS, Pan L, Ferrara JL. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood. 1997;90:3204–13.
Reddy P, Ferrara JL. Immunobiology of acute graft-versus-host disease. Blood Rev. 2003;17:187–94.
Perez-Simon JA, Diez-Campelo M, Martino R, Brunet S, Urbano A, Caballero MD, et al. Influence of the intensity of the conditioning regimen on the characteristics of acute and chronic graft-versus-host disease after allogeneic transplantation. Br J Haematol. 2005;130:394–403.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transpl. 1995;15:825–8.
Pavletic SZ, Lee SJ, Socie G, Vogelsang G. Chronic graft-versus-host disease: implications of the National Institutes of Health consensus development project on criteria for clinical trials. Bone Marrow Transpl. 2006;38:645–51.
Doney KC, Weiden PL, Storb R, Thomas ED. Treatment of graft-versus-host disease in human allogeneic marrow graft recipients: a randomized trial comparing antithymocyte globulin and corticosteroids. Am J Hematol. 1981;11:1–9.
Sale GE, Shulman HM, McDonald GB, Thomas ED. Gastrointestinal graft-versus-host disease in man. A clinicopathologic study of the rectal biopsy. Am J Surg Path. 1979;3:291–9.
Thompson B, Salzman D, Steinhauer J, Lazenby AJ, Wilcox CM. Prospective endoscopic evaluation for gastrointestinal graft-versus-host disease: determination of the best diagnostic approach. Bone Marrow Transpl. 2006;38:371–6.
Bergmann L, Fenchel B, Jahn B, Mitrous PS, Hoelzer D. Immunosuppressive effects and clinical response of fludarabine in refractory chronic lymphocytic leukemia. Ann Oncol. 1993;4:371–5.
Ferrara JL, Reddy P. Pathophysiology of graft-versus-host disease. Semin Hematol. 2006;43:3–10.
Rieger K, Loddenkemper C, Maul J, Fietz T, Wolff D, Terpe H, et al. Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD. Blood. 2006;107:1717–23.
Acknowledgments
We appreciate the work of the staff of hematopoietic stem cell transplantation unit, National Cancer Center Hospital in Japan, who provided excellent patient and donor care. We would like to express thanks to Ms. Miura and Kina for their kind technical assistance.
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Yamasaki, S., Miyagi-Maeshima, A., Kakugawa, Y. et al. Diagnosis and evaluation of intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation following reduced-intensity and myeloablative conditioning regimens. Int J Hematol 97, 421–426 (2013). https://doi.org/10.1007/s12185-013-1297-9
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DOI: https://doi.org/10.1007/s12185-013-1297-9