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).
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.
Kröger
Nicolaus
N
Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Germany.
Einsele
Hermann
H
Wolff
Daniel
D
Casper
Jochen
J
Freund
Mathias
M
Derigs
Günter
G
Wandt
Hannes
H
Schäfer-Eckart
K
K
Wittkowsky
Georg
G
Schmitz
Norbert
N
Krüger
William
W
Zabelina
Tatjana
T
Renges
Helmut
H
Ayuk
Francis
F
Krüll
Andreas
A
Zander
Axel
A
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
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D002066:Busulfan