Reduced intensity conditioning regimens Low-intensity conditioning and hematopoietic stem cell transplantation in patients with renal and colon carcinoma P Hentschke 1,2 , L Barkholt 1,2 , M Uzunel 1,2 , J Mattsson 1,2 , P Wersa¨ ll 5 , P Pisa 5 , J Martola 3 , N Albiin 3 , A Wernerson 2 , M So¨derberg 2 , M Remberger 1,2 , A Tho¨ rne 4 and O Ringde´n 1,2 1 CenterforAllogeneicStemCellTransplantation,HuddingeUniversityHospital,Stockholm,Sweden; 2 DivisionofImmunology, MicrobiologyandPathology,HuddingeUniversityHospital,Stockholm,Sweden; 3 DepartmentofRadiology,HuddingeUniversity Hospital,Stockholm,Sweden; 4 DepartmentofSurgery,HuddingeUniversityHospital,Stockholm,Swedenand 5 Departmentof Oncology,KarolinskaUniversityHospital,KarolinskaInstitutet,Stockholm,Sweden Summary: We have evaluated whether allogeneic hematopoietic stem cell transplantation (HSCT) could induce an antitumor effect in patients with metastatic solid tumors. A total of 12 HLA-identical siblings and 6 HLA-A-, -B- and –DRb1-compatible unrelated grafts were used. Diagnoses were adenocarcinoma of kidney (n ¼ 10), colon (n ¼ 6), breast (n ¼ 1) and cholangiocarcinoma (n ¼ 1). Condition- ing was fludarabine 30 mg/m 2 /day for 3 days and 2 Gy of total body irradiation. Recipients of unrelated HSCT were also given thymoglobuline and two additional days of fludarabine. The median CD34+ cell dose was 7.5  10 6 / kg. Immunosuppression was mycophenolate mofetil and cyclosporin. Among all, 12 patients became complete donor chimeras within a median of 28, 29 and 65 days for B, myeloid and T cells, respectively. Two patients rejected the grafts, one developed marrow aplasia and three were mixed chimeras. The probability of grades II–IV acute graft-versus-host-disease (GVHD) was 57%. Regression of all tumor metastases was seen in one patient with colon carcinoma. Another patient with colon and two with renal carcinoma had regression of lung metastases, but progression of metastases in the liver and/or bone. Necrosis of lung metastasis was found in one further patient with renal carcinoma who died of graft-versus- host-disease (GVHD). In all, 10 patients died; four of transplant-related complications, one of trauma and five of progressive disease. Thus, progression was common after allogeneic HSCT in unselected patients with advanced solid tumors. However, the regression of some metastases associated with GVHD provides suggestive evidence that the GVHD effect may occur in renal and colon adenocarcinoma using reduced intensity condition- ing. Bone Marrow Transplantation (2003) 31, 253–261. doi:10.1038/sj.bmt.1703811 Keywords: reduced intensity conditioning; stem cell transplantation; solid tumor The immune system is known to induce tumor regression. 1 Following allogeneic hematopoietic stem cell transplanta- tion (HSCT), graft-versus-host disease (GVHD) has been found to contribute to an antileukemic effect. 2,3 An alloresponse of donor T lymphocytes is most probably the cause of GVHD and the graft-versus-leukemia (GVL) effect. 4 An allogeneic graft-versus-tumor (GVT) effect has also been reported in breast and renal metastatic carcinoma. 5–9 When performing HSCT, lethal myeloablative condition- ing to eradicate leukemia and induce marked immuno- suppression to pave the way for the donor immunohema- topoietic system has been the routine for several dec- ades 1013 . However, this approach has been challenged by using lower doses and less toxic conditioning to induce immunosuppression and take advantage of the GVT effect later rather than the antitumor effect of chemoradiother- apy. 14–19 Inspired by the nonmyeloablative conditioning and the demonstrated allogeneic antitumor effect in renal carcino- ma patients, 8,9 we used a low-intensity conditioning protocol and included patients with not only renal but also other solid tumors, such as adenocarcinoma of colon and breast as well as cholangiocarcinoma in liver. The aim was to evaluate engraftment and complications following HSCT, and whether HSCT could induce an antitumor effect in patients with various solid tumors. Material and methods Patients Between August 1999 and January 2001, 10 patients with metastatic adenocarcinoma of kidney (R1–R10), six with colon (C1–C6) and one with breast adenocarcinoma (B1) as well as one with cholangiocarcinoma in liver hilum, Klatskin tumor (L1), were treated with reduced intensity conditioning and allogeneic peripheral HSCT at Huddinge University Hospital. All 18 patients had been considered to have Received 29 May 2002; accepted 01 September 2002 Correspondence: L Barkholt, Center for Allogeneic Stem Cell Trans- plantation B87, Huddinge University Hospital, Stockholm SE-141 86, Sweden Bone Marrow Transplantation (2003) 31, 253–261 & 2003 Nature Publishing Group All rights reserved 0268-3369/03 $25.00 www.nature.com/bmt