Graftversusmyeloma Effect And Donor Lymphocyte Infusion

Similar to chronic myelogenous leukemia, there are several lines of indirect evidence supporting the existence of an alloimmune antimyeloma response, or GvM effect. This evidence includes the observation that molecular remissions are more common after allo-geneic transplantation than after autologous transplantation in patients with myeloma.16 In addition, the relapse rates are lower after allogeneic transplant compared with autologous transplantation. Some patients with persistent evidence of disease after allo-geneic transplantation gradually achieve complete remission without further therapy. Finally, it has been shown that vaccination of the allogeneic donor against the patient's idiotypic protein can facilitate transfer of donor immunity to myeloma at the time of transplantation.37

Studies of donor lymphocyte infusion (DLI) provide direct evidence of the existence of a GvM effect38-41 (Table 85.2). The overall response rate to DLI in patients with myeloma approaches 45%, with complete responses noted in about 25% of patients. Durable complete responses are noted in half of the patients who obtain a complete remission, with follow-up over 7 years in some patients. Interestingly, extramedullary recurrence has been noted in some patients.45

DLI in patients with myeloma is associated with a high incidence of GvHD. In one study of 13 patients treated with DLI, 66% developed evidence of acute GvHD and 56% chronic GvHD.38 Quantitative PCR has been used to follow patients after DLI and demonstrates the close correlation between the onset of GvHD and GvM.46 Strategies explored to reduce GvHD following DLI include the infusion of lower numbers of donor cells, infusion of selective donor cell populations such as CD4+ cells,4047 or use of T cells transduced with thymidine kinase, which allows for systemic treatment of the recipient with ganciclovir in the event that severe GvHD develops.48-50 Lokhorst and colleagues reported responses in some patients with doses as low as 1 X 107 CD3+ cells/kg.51

There is a strong association between GvHD and a GvM effect, and whether GvHD and GvM are distinct remains unclear. A review of DLI studies in patients with multiple myeloma reported that 18 of 22 patients who developed GvHD responded to the infusion, while only 2 of 7 patients who did not develop GvHD responded.41 A second study of 54 patients demonstrated an overall response rate of 52%, with 73% of patients who developed evidence of chronic GvHD responding to DLI.52 Responses to DLI have occurred in the absence of clinical GvHD, and several patients remain in durable remission without evidence of GvHD, suggesting that GvM may indeed be separable from GvHD in some patients. In an attempt to prevent relapse and to induce a GvM effect in the minimal disease setting, prophylactic DLI after myeloablative transplantation has been explored.

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