• Irena Preložnik-Zupan Klinični oddelek za hematologijo Klinični center Zaloška 7 1525 Ljubljana
  • Samo Zver Klinični oddelek za hematologijo Klinični center Zaloška 7 1525 Ljubljana
  • Jože Pretnar Klinični oddelek za hematologijo Klinični center Zaloška 7 1525 Ljubljana
Keywords: allogeneic haematopoietic stem cell transplantation, acute graft versus host disease


Background. Beside greater susceptibility to infections, acute graft host disease is a consequence of the activation of donor T-cells against host antigens. Most common target organs are skin, liver and intestinal mucosis.

Methods. In the 6-year period between January 1995 and December 2000, 49 patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT) in Transplant unit, Department of Hematology, Clinical Centre Ljubljana. The standard GVHD prophylaxis regimen consisted of cyclosporine and short-course methotrexate. Severe, grade III-IV aGVHD with skin and/or gastrointestinal and/or liver involvement appeared in 16 (32%) of the 49 patients.

Results. Among the 16 patients with severe aGVHD, 14 had liver involvement, ten gastrointestinal and eight skin involvement. One patient had skin involvement only, the rest of them had combined involvement of two or three organ systems. Routine first-line treatment for aGVHD, given to all 16 pts with severe forms of the disease, was methylprednisolone (MP) 2mg/ kg. Six patients with predominant skin involvement responded to MP. Other ten patients with mainly liver and gastrointestinal involvement needed second or even third line aGVHD treatment. These were anti-thymocyte globulin (ATG) and/or monoclonal antibodies (OKT3) and/or mycophenolate mofetil (MMF) and/or FK506 (tacrolimus). Seven patients died of advanced aGVHD and treatment related infection.

Conclusions. Based on our experiences, we conclude that in critically ill patients with severe aGVHD, neutropenia and high risk for opportunistic infection, each day of ineffective MP therapy may have fatal consequences. Simultaneous institution of a combination of corticosteroids and a second-line drug might prove more appropriate for patients with a severe form of aGVHD.


Download data is not yet available.


Apperley JF, Gluckman E, Gratwohl A. Blood and marrow transplantation. The EBMT Handbook. 2000 Revised Edition. Paris: European School of Haematology, 2000: 135–51.

Gale RP, Bortin MM, van Bekkum DW et al. Risk factors for acute graft versus host disease. Brit J Haematol 1987; 67: 397–406.

Nash RA, Pepe MS, Storb R et al. Analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Blood 1992; 80: 1838–45.

Przepiorka D, Smith TL, Folloder J et al. Risk factors for acute graft-versushost disease after allogeneic blood stem cell transplantation. Blood 1999; 94: 1465–70.

Basara N, Blau IW, Willenbacher W et al. New strategies in the treatment of graft-versus-host-disease. Bone Marrow Transplant 2000; 25: S12–5.

Ruutu T, Niederwieser D, Gratwohl A et al. A survey of the prophylaxis and treatment of acute GVHD in Europe: a report of the European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 1997; 19: 759–64.

Van Lint MT, Uderzo C, Locasciuli A et al. Early treatment of acute graftversus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation. Blood 1998; 92: 2288–93.

Basara N, Blau IW, Roemer E et al. Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. Bone Marrow Transplant 1998; 22: 61–5.

Hebart H, Gischeidle H, Holler E et al. OKT3 for steroid-resistant acute GVHD: a three-center experience. Bone Marrow Transplant 1999; 23: Suppl: 301a–1.

Storb R, Deeg HJ, Whitehead J et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 1986; 314: 729–35.

Storb R, Pepe M, Deeg HJ et al. Long-term follow-up of a controlled trial comparing a combination of methotrexate plus cyclosporine with cyclosporine alone for prophylaxis of graft-versus-host disease in patients administered HLA-identical marrow grafts for leukemia. Blood 1992; 80: 560–1.

How to Cite
Preložnik-Zupan I, Zver S, Pretnar J. SEVERE (GRADE III-IV) ACUTE GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION. ZdravVestn [Internet]. 1 [cited 22Sep.2019];71(9). Available from:
Professional Article