Bone Marrow Transplantation (2001) 28, 1161–1166  2001 Nature Publishing Group All rights reserved 0268–3369/01 $15.00 www.nature.com/bmt Case report A graft-versus-colonic cancer effect of allogeneic stem cell transplantation H Zetterquist 1 , P Hentschke 2 , A Tho ¨rne 1 , A Wernerson 3 , J Mattsson 2 , M Uzunel 2 , J Martola 4 , N Albiin 4 , J Aschan 2 , N Papadogiannakis 3 and O Ringde ´n 2 1 Department of Surgery, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden; 2 Centre for Allogeneic Stem Cell Transplantation and Department of Clinical Immunology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden; 3 Department of Pathology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden; and 4 Department of Radiology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden Summary: Allogeneic stem cell transplantation (ASCT) has proved to have an important immune-mediated anti-tumour effect in patients with haematologic malignancies. There is also evidence of such an effect in patients with malig- nant tumours. We studied this effect of ASCT in a patient with colorectal cancer. A 77-year-old man hav- ing a primarily resected colonic cancer with dissemi- nated lymph node involvement received ASCT from his HLA-identical sibling as the only treatment. Mixed haematopoietic chimerism was monitored using PCR- amplification of variable number tandem repeats and tumour size, assessed by repeated CT scans. Recipient leucocytes were gradually replaced by donor cells for 1 month. Continuous resolution of lymph node metastases was seen together with clinical graft-versus-host disease (GVHD). The patient died of pneumonia and cardiac insufficiency 4 months after transplantation. At autopsy, most of the metastases were necrotic, with few remain- ing tumour cells. Clinical and histopathological post- mortem results showed a graft-versus-colorectal cancer effect. Bone Marrow Transplantation (2001) 28, 1161– 1166. Keywords: allogeneic stem cell transplantation; graft- versus-host disease; colonic carcinoma; graft-versus- tumour; mixed chimerism Cancer may be controlled by the immune system as shown in experimental animal studies and in man. 1–3 Patients with leukaemia who develop acute graft-versus-host disease (GVHD) and, especially chronic GVHD, run a lower risk of relapse than those without GVHD. 4–6 Furthermore, T cell depletion of the graft, which effectively prevents GVHD, increases the risk of relapse. 7–9 A graft-versus-tumour (GVT) effect has been found in animal models, 10,11 human Correspondence: Dr O Ringde ´n, Department of Clinical Immunology, Karolinska Institutet, Huddinge University Hospital, F79, SE-141 86 Stockholm, Sweden Received 16 May 2001; accepted 2 September 2001 myeloma and breast cancer. 12,13 Promising results after ASCT have also been reported in patients with hyper- nephroma. 14,15 Recently, more attention has been paid to the use of gra- nulocyte colony-stimulating factor (G-CSF)-mobilized per- ipheral blood stem cell transplantation. Comparison of G- CSF-mobilized ASCT (containing at least a 10-fold increase in donor T cell numbers) and traditional bone mar- row transplantation reveals a similar incidence of GVHD and graft-versus-leukaemia (GVL) effect. 16–19 Since donor T cells are the effectors of the GVL effect, it is important to study whether G-CSF-mobilized allogeneic stem cells maintain a reasonably high antitumour effect, as also in other malignancies, with a minimum of GVHD. We wished to study the clinical contributions of the GVT effect and GVHD in a patient with colonic cancer after non- myeloablative ASCT. Materials and methods Patient and donor A 77-year-old man, who had undergone peripheral vascular surgery and coronary by-pass surgery, was diagnosed as having sigmoid cancer and underwent a left-sided hemico- lectomy in April 1998. Histopathological examination revealed an adenocarcinoma Dukes C, with metastases in six of 12 local lymph nodes. With his history of severe vascular disease, he was not considered a candidate for adjuvant cytostatic therapy. At 1-year follow-up, he was found to have enlarged coeliac lymph nodes and a needle biopsy confirmed metastatic adenocarcinoma. As he had several healthy siblings, he was given the option of undergoing ASCT and was ultimately found to have a well- suited donor in his healthy 66-year-old HLA-identical brother. ASCT for metastatic colonic carcinoma using non- myeloablative conditioning was approved by the ethics committee at Huddinge University Hospital. Allogeneic stem cell transplantation The patient received fludarabine (30 mg/m 2 ) i.v. on days -4, -3 and -2 before transplantation. On the day of trans-