Autologous graftversushost disease

Although the high rate of relapse after autologous HSCT has in part been attributed to tumor contamination of the autograft, a similar relapse rate has also been observed with syngeneic HSCT, which is free of tumor contamination.21 It is more likely that relapses are due to endogenous tumor cells that survived the cytotoxic effects of the conditioning regimen. It has been hypothesized that these high relapse rates with either syngeneic or autologous HSCT are due to the absence of a GVL effect. Attempts have been made to induce GVHD and an associated GVL effect in the autologous HSCT setting. Murine studies indicated that administration of the immunosuppressive drug cyclosporine after autologous HSCT elicited an autoimmune syndrome with pathology virtually identical to GVHD.73 The GVHD observed after autologous and syngeneic HSCT in murine models was associated with the development of a highly restricted repertoire of CD8+ autoreactive T cells that recognized a peptide from the invariant chain, termed CLIP, presented by MHC class II molecules.74 These autoreactive T cells produced type 1 cytokines, including interferon-gamma, interleukin-2 (IL-2), and TNF-a. These studies led to clinical trials in patients with lymphoma and acute leukemia.75 76 Although clinical and histologic evidence of GVHD was demonstrated in these trials, there was no clear evidence of a clinical benefit in terms of a reduction in relapse rates.

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