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Reduced Intensity Conditioning Regimens

Low-intensity conditioning and hematopoietic stem cell transplantation in patients with renal and colon carcinoma

Bone Marrow Transplantation volume 31, pages 253–261 (2003)Cite this article

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 –DRβ1-compatible unrelated grafts were used. Diagnoses were adenocarcinoma of kidney (n=10), colon (n=6), breast (n=1) and cholangiocarcinoma (n=1). Conditioning was fludarabine 30 mg/m2/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 7.5×106/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 conditioning.

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Acknowledgements

We thank the staff at the Center for Allogeneic Stem cell Transplantation for competent and compassionate patient care, Inger Hammarberg for help with the preparation of this manuscript and Dr Zoe and Francis Walsh for checking the language. This study was supported by the Swedish Cancer Society (0070-B99-13XAC), the Children's Cancer Foundation (1997/073), the Swedish Medical Research Council (K2000-06X-05971-20A), the Cancer Society in Stockholm, the Tobias Foundation and the FRF Foundation.

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Authors and Affiliations

  1. Center for Allogeneic Stem Cell Transplantation, Huddinge University Hospital, Stockholm, Sweden

    P Hentschke, L Barkholt, M Uzunel, J Mattsson, M Remberger & O Ringdén

  2. Division of Immunology, Microbiology and Pathology, Huddinge University Hospital, Stockholm, Sweden

    P Hentschke, L Barkholt, M Uzunel, J Mattsson, A Wernerson, M Söderberg, M Remberger & O Ringdén

  3. Department of Radiology, Huddinge University Hospital, Stockholm, Sweden

    J Martola & N Albiin

  4. Department of Surgery, Huddinge University Hospital, Stockholm, Sweden

    A Thörne

  5. Department of Oncology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

    P Wersäll & P Pisa

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Hentschke, P., Barkholt, L., Uzunel, M. et al. Low-intensity conditioning and hematopoietic stem cell transplantation in patients with renal and colon carcinoma. Bone Marrow Transplant 31, 253–261 (2003). https://doi.org/10.1038/sj.bmt.1703811

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