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Blood, 15 August 2001, Vol. 98, No. 4, pp. 934-939

CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

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

Edwin Alyea, Edie Weller, Robert Schlossman, Christine Canning, Iain Webb, Deborah Doss, Peter Mauch, Karen Marcus, David Fisher, Andrea Freeman, Bijal Parikh, John Gribben, Robert Soiffer, Jerome Ritz, and Kenneth Anderson

From the Center for Hematologic Oncology and Department of Biostatistics, Dana-Farber Cancer Institute, Departments of Medicine and Radiation Therapy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

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. Exploitation of this strategy remains of interest because donor lymphocyte infusions (DLIs) can induce a potent graft-versus-myeloma (GVM) effect. CD6 T-cell-depleted allogeneic BMT was combined with prophylactic CD4+ DLI administered 6 to 9 months after BMT in an effort to reduce TRM and to induce a GVM 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) prophylaxis. GVHD after BMT was minimal, 1 (4%) grade III and 4 (17%) grade II GVHD. Fourteen patients received DLI, 3 in complete response and 11 with persistent 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 (>=  II) or extensive chronic GVHD. Two-year estimated overall survival 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 patients who underwent CD6-depleted BMT survived 6 months with no GVHD and did not receive DLI (41%) (P = .13). Although this study suggests that prophylactic DLI induces significant GVM responses after allogeneic BMT, only 58% of patients were able to receive DLI despite T-cell-depleted BMT. Therefore, less toxic transplantation strategies are needed to allow a higher proportion of patients to receive DLI and the benefit from the GVM effect after transplantation.

© 2001 by The American Society of Hematology.
 

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