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Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors

Nature Clinical Practice Oncology volume 5, pages 256–267 (2008)Cite this article

Abstract

Allogeneic transplantation of hematopoietic cells from an HLA-compatible donor has been used to treat hematologic malignancies. Allogeneic transplantation not only replaces the marrow affected by the disease, but exerts an immune graft-versus-tumor (GVT) effect mediated by donor lymphocytes. The development of nonmyeloablative conditioning regimens before allogeneic transplantation has allowed this therapy to be used in elderly and disabled patients. An allogeneic GVT effect is observed in a proportion of patients with renal, breast, colorectal, ovarian, and pancreatic cancer treated with allogeneic transplantation. In general, the tumor response is associated with the development of acute and chronic graft-versus-host disease. Further improvements will depend on the identification of the antigen targets of GVT, and on reduction of the toxicity of the procedure. Targeted therapies may complement the immune effect of allogeneic transplantation. We present updated results from the literature and data recently placed on file at the European Bone Marrow Transplantation Solid Tumors Working Party.

Key Points

  • Allogeneic stem-cell transplantation from a HLA-compatible sibling donor or from a matched unrelated donor is a beneficial treatment for patients with relapsed and high-risk hematological malignancies

  • Radiotherapy and/or chemotherapy are administered before allotransplant for cytoreduction of the disease and for ablation of the patient's immune system, thus allowing engraftment of infused cells; the newly introduced nonmyeloablative or reduced-intensity regimens are purely immunosuppressive

  • T cells in the infused transplant facilitate engraftment and exert an immune attack on the patient's leukemia/tumor cells, the so-called “graft-versus-leukemia/tumor” effect

  • Retrospective analyses and prospective pilot studies demonstrate a graft-versus-tumor effect in solid tumors, particularly in advanced, clear-cell renal cancer, but also in breast, ovarian, colorectal and pancreatic carcinoma, and soft-tissue sarcoma

  • The mechanisms of the graft-versus-tumor effect are still poorly understood: an immune reaction by donor T cells against minor histocompatibility antigens or tumor-associated antigens is most probably involved

  • Allogeneic transplantation in renal cancer and other solid tumors should be considered a developmental therapy until definitive proof of a clinical benefit is achieved by current studies

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Figure 1: Allotransplantation in solid tumors at EBMT centers during the period 1995–2005.

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Acknowledgements

We thank the doctors, nurses, and patients who have been involved in the mentioned studies. A special thank you to M Carmen Ruiz de Elvira for providing the EBMT data. The EBMT Group is partially supported by an AIRC Regional Grant to MB and PP.

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Authors and Affiliations

  1. T Demirer and G Gurman are Professors in the Department of Haematology/Oncology, F Arpaci is Professor in the Department of Medical Oncology, Ankara University Medical School, Turkey,

    Taner Demirer, Fikret Arpaci & Gunhan Gurman

  2. L Barkholt is Associate Professor, Karolinska University Hospital Huddinge, Sweden,

    Lisbeth Barkholt

  3. D Blaise is Professor in the Institut Paoli Calmettes, France,

    Didier Blaise

  4. P Pedrazzoli is Vice-Director of the Falck Division of Medical Oncology, Ospedale Niguarda-Ca' Granda, Milano,

    Paolo Pedrazzoli

  5. M Aglietta is Professor of Medical Oncology, Institute for Cancer Research and Treatment, Candiolo (Torino),

    Massimo Aglietta

  6. Divisione di Ematologia, AM Carella is Director, Azienda Ospedaliera Universitaria San Martino, Genova,

    Angelo Michele Carella

  7. G Rosti is Director, Medical Oncology, Ospedale Regionale, Treviso,

    Giovanni Rosti

  8. M Bregni is Director of the Strategic Program in Oncology, Istituto Scientifico San Raffaele, Italy,

    Marco Bregni

  9. J-O Bay is Professor at Fédération de Greffe de Moelle et de Thérapie Cellulaire d'Auvergne, Centre Jean Perrin-CHU Clermont-Ferrand, France,

    Jacques-Olivier Bay

  10. D Niederwieser is Professor in the Division of Hematology/Oncology, University Hospital Leipzig, Germany.,

    Dietger Niederwieser

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  1. Taner Demirer
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  2. Lisbeth Barkholt
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Correspondence to Marco Bregni.

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Demirer, T., Barkholt, L., Blaise, D. et al. Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors. Nat Rev Clin Oncol 5, 256–267 (2008). https://doi.org/10.1038/ncponc1104

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