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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.

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