T-cell-depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect

Previous trials of allogeneic bone marrow transplantation (BMT) in patients with multiple myeloma (MM) have demonstrated high response rates but also high transplantation-related mortality (TRM) and high relapse rates. Exploi tation of this strategy remains of interest because donor lymphocyte infusi ons (DLIs) can induce a potent graft-versus-myeloma (GVM) effect. CD6 T-cel l-depleted allogeneic BMT was combined with prophylactic CD4(+) DLI adminis tered 6 to 9 months after BMT in an effort to reduce TRM and to induce a GV M response after BMT. Twenty-four patients with matched sibling donors and chemotherapy-sensitive disease underwent BMT. CD6 T-cell depletion of donor bone marrow was the sole method of graft-versus-host disease (GVHD) prophy laxis. GVHD after BMT was minimal, 1 (4%) grade III and 4 (17%) grade II GV HD. Fourteen patients received DLI, 3 in complete response and 11 with pers istent disease after BMT. Significant GVM responses were noted after DLI in 10 patients with persistent disease, resulting in 6 complete responses and 4 partial responses. After DLI, 50% of patients developed acute (greater t han or equal to 11) or extensive chronic GVHD. Two-year estimated overall s urvival and current progression-free survival (PFS) for all 24 patients is 55% and 42%, respectively. The 14 patients receiving DLI had an improved 2- year current PFS (65%) when compared with a historical cohort of MM patient s who underwent CD6-depleted BMT survived 6 months with no GVHD and did not receive DLI (41 %) (P = .13). Although this study suggests that prophylact ic DLI induces significant GVM responses after allogeneic BMT, only 58% of patients were able to receive DLI despite T-cell-depleted BMT. Therefore, l ess toxic transplantation strategies are needed to allow a higher proportio n of patients to receive DLI and the benefit from the GVM effect after tran splantation. (C) 2001 by The American Society of Hematology.