title: Myeloablative intensified conditioning regimen with in vivo T-cell depletion (ATG) followed by allografting in patients with advanced multiple myeloma. A phase I/II study of the German Study-group Multiple Myeloma (DSMM).
abstract: We investigated toxicity and efficacy of in vivo T-cell depletion with anti-thymocyte globulin (ATG) as part of an intensified myeloablative conditioning regimen followed by allogeneic stem cell transplantation in patients with advanced multiple myeloma. The conditioning regimen consisted of modified total body irradiation, busulfan and cyclophosphamide (n=15) or in the case of prior dose-limiting radiotherapy of busulfan and cyclophosphamide (n=3). The median age was 44 years (range, 29-53) and the median time from diagnosis to transplant was 12 months (range, 6-144). Grade II-IV acute graft-versus-host disease (GvHD) occurred in six patients (35%). Severe grade III/IV GvHD developed in one patient (6%). Three patients died of therapy-related causes (17%). A complete remission (CR) with negative immunofixation after allogeneic transplantation was seen in eight of the evaluable patients (53%). After a median follow-up of 41 months (range, 8-84), the estimated overall survival at 6 years for all patients is 77% (CI 95%: 58-96%). The estimated progression-free survival at 6 years for all patients is 31% (CI 95%: 2-59%) and 46% (CI 95%: 9-83%) for patients with CR. In vivo T-cell depletion with ATG resulted in a low rate of severe GvHD with low treatment-related mortality, and a substantial number of long-term survivors.
authors.affiliation: Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
authors.forename: Jochen
authors.initials: J
authors.lastname: Casper
authors.forename: Mathias
authors.initials: M
authors.lastname: Freund
authors.forename: Günter
authors.initials: G
authors.lastname: Derigs
authors.forename: Hannes
authors.initials: H
authors.lastname: Wandt
authors.forename: K
authors.initials: K
authors.lastname: Schäfer-Eckart
authors.forename: Georg
authors.initials: G
authors.lastname: Wittkowsky
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: William
authors.initials: W
authors.lastname: Krüger
authors.forename: Tatjana
authors.initials: T
authors.lastname: Zabelina
authors.forename: Helmut
authors.initials: H
authors.lastname: Renges
authors.forename: Francis
authors.initials: F
authors.lastname: Ayuk
authors.forename: Andreas
authors.initials: A
authors.lastname: Krüll
authors.forename: Axel
authors.initials: A
authors.lastname: Zander
mesh_terms: D000208:Acute Disease; D000328:Adult; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000627:therapeutic use; D002908:Chronic Disease; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000145:classification / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000401:mortality; D014916:Whole-Body Irradiation
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D002066:Busulfan