Chronic Myelogenous Leukemia

Chronic myelogenous leukemia is highly susceptible to the GVL effect, as evidenced by the response of CML to DLI, and that long-term, leukemia-free survival rates exceed 70% for patients who were transplanted in early chronic phase.8990 GVL effect against CML clearly exists, as the greatest efficacy of DLI has been demonstrated in CML. Several studies have implicated peptides associated with the product of bcr-abl, but a specific antigen has yet to be identified.91 However, studies in CML provide several important insights on the efficacy of DLI in specific, and GVL in general, relative to disease status and lymphocyte dose.22'52'53'92 Chronic phase CML is particularly responsive to DLI, with remission rates of 50-80%.53'92 In contrast, response rates of accelerated and acute ("blast") phase CML varies between 10% and 30%; the more advanced states of the CML are inversely correlated to the response to DLI. These variable response rates reflect the biology of disease relative to antigen and MHC presentation, as well as growth rate. In patients with more advanced CML, the GVL effect may be insufficiently potent to be clinically detectable, because the leukemic growth rate exceeds the ability of the immune effect to eliminate disease. There is also considerable variability of response to DLI among CML patients in chronic phase. For CML patients with cytogenetic or molecular relapses, the response rates are approximately 60-70% and 80-90%, respectively.53,92 In contrast, the response to DLI among patients with chronic phase CML with morphologic or hematologic relapses is approximately 50-60%. Increased lymphocyte dose appears to improve DLI efficacy against relapse, but it is also associated with increased toxicity in the form of GVHD.92 However, lower DLI doses are as effective as higher doses in patients with a low disease burden. These variations in response suggest that tumor bulk plays an important role in the efficacy of DLI in CML. All of these factors, including disease biology, disease state, and tumor bulk, appear to play significant roles relative to the susceptibility of hematologic malignancies to a GVL effect. Autologous HSCT has limited efficacy in CML due to the relative lack of sensitivity of CML cells to cytotoxic therapy, and more importantly due to difficulty in obtaining a relatively tumor-free auto-graft.93 Due to the tremendous clinical success of ima-tinib (STI-571, Gleevec), the emerging predominant strategy is to use allogeneic HSCT in patients with more advanced CML, and for patients who have failed or progressed on Gleevec.94

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