title: Long-term follow-up of T cell-depleted allogeneic bone marrow transplantation in refractory multiple myeloma: importance of allogeneic T cells.
abstract: Multiple myeloma may be cured by myeloablative conditioning and allogeneic blood or marrow transplantation (alloBMT), but this occurs at the expense of high transplant-related mortality. In an endeavor to reduce procedure-related toxicity, this study retrospectively evaluated the safety, tolerability, and efficacy of T cell depletion by counterflow centrifugal elutriation before alloBMT. Fifty-one patients with stage II (6) or III (45) multiple myeloma received alloBMTs using T cell depletion by elutriation. Fifty-three percent (27 of 51) of patients had primary refractory disease at the time of transplantation, 10% (5 of 51) had relapsed disease, and 4% (2 of 51) had refractory relapsed disease. The median age was 49 (range, 32 to 62) years, and the median time from diagnosis to transplantation was 9 (range, 4 to 58) months. Patients had received a median of 1 (range, 1 to 3) regimen and 4 (range, 2 to 16) cycles of chemotherapy. In this population, transplant-related mortality rate was 24% (12 of 51) with 2 patients dying of graft-versus-host disease (GVHD). Thirty-one of 39 evaluable patients have experienced relapse, and the probability of progression-free survival 5 years after alloBMT alone is 16%. Sixteen patients were given donor lymphocyte infusions (DLI) at the time of relapse (n = 11) or for persistent disease 1 year after transplantation (n = 5). Acute or chronic GVHD was seen in 63% (10 of 16) of patients given DLI. Responses were seen in 8 of 16 patients (6 complete response [CR], 2 partial response [PR]) with 6 of 8 responding patients having GVHD. Five recipients of DLI remain in a continuous CR, ranging from 3 to 64 months in duration. Thus, like chronic myelogenous leukemia, allogeneic T cells appear to have potent antimyeloma activity that is critical for achieving a cure. DLI-induced remissions of multiple myeloma can be durable, even in patients with refractory multiple myeloma. Unlike chronic myelogenous leukemia, the antimyeloma effect of allogeneic T cells rarely occurs in the absence of clinically significant GVHD.
authors.affiliation: Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Baltimore, MD, USA. huffca@jhmi.edu
authors.forename: Carol Ann
authors.initials: CA
authors.lastname: Huff
authors.forename: Ephraim J
authors.initials: EJ
authors.lastname: Fuchs
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Noga
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Donnell
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ambinder
authors.forename: Louis
authors.initials: L
authors.lastname: Diehl
authors.forename: Ivan
authors.initials: I
authors.lastname: Borrello
authors.forename: Georgia B
authors.initials: GB
authors.lastname: Vogelsang
authors.forename: Carole B
authors.initials: CB
authors.lastname: Miller
authors.forename: Ian A
authors.initials: IA
authors.lastname: Flinn
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brodsky
authors.forename: Deborah
authors.initials: D
authors.lastname: Marcellus
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jones
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome