title: Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality.
abstract: We investigated the feasibility of unrelated stem cell transplantation in 21 patients with advanced stage II/III multiple myeloma after a reduced-intensity conditioning regimen consisting of fludarabine (150 mg/m(2)), melphalan (100-140 mg/m(2)), and antithymocyte globulin (ATG; 10 mg/kg on 3 days). The median patient age was 50 years (range, 32-61 years). All patients had received at least one prior autologous transplantation, in 9 cases as part of an autologous-allogeneic tandem protocol. No graft failure was observed. At day 40 complete donor chimerism was detected in all patients. Grade II to IV acute graft-versus-host disease (GVHD) was seen in 8 patients (38%), and severe grade III/IV GVHD was observed in 4 patients (19%). Six patients (37%) developed chronic GVHD, but only 2 patients (12%) experienced extensive chronic GVHD. The estimated probability of nonrelapse mortality at day 100 was 10% and at 1 year was 26%. After allografting, 40% of the patients achieved a complete remission, and 50% achieved a partial remission, resulting in an overall response rate of 90%. After a median follow-up of 13 months, the 2-year estimated overall and progression-free survival rates are 74% (95% CI, 54%-94%) and 53% (95% CI, 29%-87%), respectively. A shorter progression-free survival was seen in patients who already experienced relapse to prior autograft (26% versus 86%, P =.04). Dose-reduced conditioning with pretransplantation ATG followed by unrelated stem cell transplantation provides durable engraftment and donor chimerism, reduces substantially the risk of transplant-related organ toxicity, and induces high remission rates.
authors.affiliation: Department of Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Germany. nkroeger@uke.uni-hamburg.de
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Herbert Gottfried
authors.initials: HG
authors.lastname: Sayer
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.forename: Michael
authors.initials: M
authors.lastname: Kiehl
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Helmut
authors.initials: H
authors.lastname: Renges
authors.forename: Tatjana
authors.initials: T
authors.lastname: Zabelina
authors.forename: Boris
authors.initials: B
authors.lastname: Fehse
authors.forename: Francis
authors.initials: F
authors.lastname: Ayuk
authors.forename: Georg
authors.initials: G
authors.lastname: Wittkowsky
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: Axel Rolf
authors.initials: AR
authors.lastname: Zander
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D005240:Feasibility Studies; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000961:Antilymphocyte Serum; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan