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Reply to the letter by Hori et al

Bone Marrow Transplantation volume 33, pages 257–258 (2004)Cite this article

Hori et al have raised an important question, namely the response evaluation criteria for use in immunotherapy. We used the combined results of computer tomography (CT) images and autopsy findings showing a decrease in size and/or number of metastases, and cell necrosis of metastases after the reduced intensity conditioning (RIC) and allogeneic stem cell transplantation (SCT) in patients with metastatic solid organ cancer.1 Childs et al also relied on CT image changes not only in evaluation of the effect of the RIC and allogeneic SCT, but also when deciding which patients would be offered therapy.2 Mainly patients with slowly progressive tumour metastases were included in the experimental protocol at the National Institute of Health (NIH).3 We agree that an urgent need exists for validation of the tumour response criteria which can hardly directly adapt the Response Evaluation Criteria in Solid Tumours (RECIST) mainly used after chemoradiotherapy.3

The aim of the RIC before transplantation is not to reduce tumour metastases, but to suppress the recipient immune system and to prevent rejection of the donor haematopoietic stem cells and maturating leucocytes. This is in contrast to the more aggressive myeloablative conditioning, which aims to kill all leukaemic cells. Until recently, this has been used mainly in patients with haematological malignancies. This patient group gains a cytotoxic antileukaemia effect by the time the preparative regimen has started. Thus, evaluation of allogeneic SCT presumes total myeloablation – no or only few malignant leukaemic cells – as the basic level to follow the developing alloimmunity against possible relapse of the haematological malignancy. However, RIC is now used in an increasing number of patients with haematological malignancies. Using sensitive molecular biological tools, a new patient group with minimal residual disease (MRD) at transplantation requires evaluation against this initial low leukaemia cell load.4 Accordingly, patients with solid tumours with a known tumour marker – such as the prostate specific antigen (PSA) of prostate cancer and the alpha-fetoprotein of hepatocellular cancer – can be evaluated with such a sensitive test, mirroring early the biological activity of the tumour. Scientific research is already focused on patients with tumour types without known tumour marker(s) to isolate specific tumour antigen(s). They may be used as immunotherapy targets and for treatment evaluation.

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References

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Authors and Affiliations

  1. Centre for Allogeneic Stem Cell Transplantation, Huddinge University Hospital, Stockholm, SE-14186, Sweden

    L Barkholt, P Hentschke & O Ringdén

  2. Department of Clinical Immunology, Division of Laboratory Medicine, Karolinska Institutet, Stockholm, SE-14186, Sweden

    L Barkholt, P Hentschke & O Ringdén

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  1. L Barkholt
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  2. P Hentschke
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  3. O Ringdén
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Barkholt, L., Hentschke, P. & Ringdén, O. Reply to the letter by Hori et al. Bone Marrow Transplant 33, 257–258 (2004). https://doi.org/10.1038/sj.bmt.1704372

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