title: T-cell--depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect.
abstract: 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 (> or = 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. (Blood. 2001;98:934-939)
authors.affiliation: Center for Hematologic Oncology and Department of Biostatistics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. edwin_alyea@dfci.harvard.edu
authors.forename: E
authors.initials: E
authors.lastname: Alyea
authors.forename: E
authors.initials: E
authors.lastname: Weller
authors.forename: R
authors.initials: R
authors.lastname: Schlossman
authors.forename: C
authors.initials: C
authors.lastname: Canning
authors.forename: I
authors.initials: I
authors.lastname: Webb
authors.forename: D
authors.initials: D
authors.lastname: Doss
authors.forename: P
authors.initials: P
authors.lastname: Mauch
authors.forename: K
authors.initials: K
authors.lastname: Marcus
authors.forename: D
authors.initials: D
authors.lastname: Fisher
authors.forename: A
authors.initials: A
authors.lastname: Freeman
authors.forename: B
authors.initials: B
authors.lastname: Parikh
authors.forename: J
authors.initials: J
authors.lastname: Gribben
authors.forename: R
authors.initials: R
authors.lastname: Soiffer
authors.forename: J
authors.initials: J
authors.lastname: Ritz
authors.forename: K
authors.initials: K
authors.lastname: Anderson
mesh_terms: D000206:Actuarial Analysis; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D018572:Disease-Free Survival; D005260:Female; D020350:Graft vs Tumor Effect / Q000502:physiology; D006801:Humans; D008212:Lymphocyte Depletion / Q000592:standards*; D017710:Lymphocyte Transfusion / Q000592:standards*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000628:therapy*; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen