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. 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)
Alyea
E
E
Center for Hematologic Oncology and Department of Biostatistics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. edwin_alyea@dfci.harvard.edu
Weller
E
E
Schlossman
R
R
Canning
C
C
Webb
I
I
Doss
D
D
Mauch
P
P
Marcus
K
K
Fisher
D
D
Freeman
A
A
Parikh
B
B
Gribben
J
J
Soiffer
R
R
Ritz
J
J
Anderson
K
K
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
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen