Allogeneic transplantation following non-myeloablative conditioning in renal carcinoma. New evidence of the immune mecha
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EDITORIAL
Allogeneic transplantation following non-myeloablative conditioning in renal carcinoma. New evidence of the immune mechanisms responsible for the activity of this form of immunotherapy and the pathogenetic role of endogenous retroviruses Camillo Porta Published online: 16 May 2008 ©Springer-Verlag 2008
Camillo Porta (쾷) Medical Oncology and Laboratory of Pre-clinical Oncology and Experimental Therapies IRCCS San Matteo University Hospital Foundation, 27100 Pavia, Italy e-mail: [email protected]
In 2000, the influential New England Journal of Medicine published the first impressive results of the use of allogeneic stem cell transplantation following nonmyeloblative conditioning (the so-called ‘mini-allo transplant’) in the treatment of patients with advanced kidney cancer [1]. Many thought that at last a highly active treatment had become available for this relatively rare pathology which until then had been almost without efficient therapy options. Exactly the same hopes had been raised for the use of high doses of IL-2 administered by intravenous bolus [2]. Therefore, like the experience of Rosenberg, the work of Childs and co-workers was subsequently subjected to intense critical review. At first, the principal criticisms concerned the lack of an adequate formal evaluation of follow-up of the patients in the original cohort presented in the New England Journal of Medicine, and also the scarse feasibility and practicability of the ‘mini-allo transplant’, a complex and costly procedure burdened with substantial morbidity and mortality rates. Later, other authors presented data which did not overall confirm the exciting results originally presented by the Bethseda group (Table 1) [3–13]. These studies were, however, based on modest numbers of highly selected patients. Recent phase III studies, irreproachable (or almost) for their methodology, have promoted the development of a variety of molecular therapies. These have shown themselves to be capable of finally having an impact on survival of patients with advanced kidney cancer [14-17]. Consequently, it seemed that the ‘mini-allo transplant’ had been definitively abandoned as a therapeutic option for these patients. In reality, as for other complex, immunotherapeutic approaches, the biggest problem was and remains understanding and defining the mechanisms by which the anti-tumor activity of the transplanted stem cells is (or is not) carried out.
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Oncol Rev (2008) 2:1–3
Table 1 Experiences reported in literature of allogeneic stem cell transplantation following non myeloablative conditioning for advanced kidney cancer. Results show the wide variation in response (from 0% to 57%) and the substantial mortality rates (from 0% to 33%) in spite of operator expertise
Author (year)
Ref. N. patients Transplant- Overall treated related response mortality (%) rate (%)
Childs et al. (2002) Bregni et al. (2002) Pedrazzoli et al. (2002) Rini et al. (2002) Ueno et al. (2003) Hentschke et al. (2003) Baron et al. (2003) Blaise et al. (2004) Nakagawa et al.
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