Donor Leukocyte Infusions Are Effective in Relapsed Multiple Myeloma After Allogeneic Bone Marrow Transplantation

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Abstract
Donor leukocyte infusions (DLI) can induce sustained remissions in patients with acute and chronic myeloid leukemia who relapse after allogeneic bone marrow transplantation (allo-BMT). Also, in multiple myeloma (MM), incidental reports have indicated the existence of a graft-versus-myeloma effect (GVM) induced by allo-reactive T cells. We performed a retrospective study in a larger group of MM patients to characterize better the effect, prognostic factors, and toxicity of this new treatment modality. Thirteen patients with relapsed MM after allo-BMT were studied. Patients received a total of 29 DLI with T-cell doses ranging from 1 × 106/kg to 33 × 107/kg. Repetitive courses, sometimes with escalated cell doses, were undertaken in case of no response to or relapse after DLI. Eight of 13 patients responded: 4 patients achieved a partial remission and 4 patients achieved a complete remission. Dose escalation was effective in 3 patients. The time to response was median 6 weeks (range, 4 to 10 weeks). Major toxicities were secondary to acute and chronic graft-versus-host disease (GVHD), which occurred in 66% and 56% of all patients and in 87% and 85% of the responders, respectively. Two responding patients developed fatal BM aplasia. The only prognostic factors for response were a T-cell dose greater than 1 × 108/kg and the occurrence of GVHD. Seven of nine patients developing acute GVHD responded, as compared with only 1 response in the 4 patients without GVHD and 6 of 7 patients with chronic GVHD responded, whereas no response was observed in the 5 patients without chronic GVHD. DLI are effective in a high percentage of patients with relapsed MM after allo-BMT, although it is associated with a high treatment-related toxicity. The dose of T cells used may be important in determining the GVM effect, with the highest probability of response after infusion of more than 1 × 108 T cells. Because the optimal individual dose may vary, patient-adapted therapy consisting of repeated infusions with escalating dose of donor leukocytes until maximum response is achieved may therefore be preferable.