Allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies after dose-escalated treosulfan/fludarabine conditioning.
OBJECTIVE
Treosulfan was introduced recently as a conditioning agent for allogeneic blood stem-cell transplantation. The favorable nonhematologic toxicity profile at 3 x 10 g/m(2) was the basis for dose escalation in this prospective, multicenter trial.


METHODS
Fifty-six patients with various hematologic malignancies who were not eligible for standard conditioning were treated with one of three doses: 10 g/m(2), 12 g/m(2), or 14 g/m(2) of intravenous treosulfan, which was administered on days -6 to -4 combined with fludarabine 30 mg/m(2) on days -6 to -2. Patients in complete remission (CR; 42%) or non-CR (58%) received grafts from matched related (47%) or matched unrelated (51%) donors; one patient had a mismatched related donor (2%).


RESULTS
No engraftment failure occurred. Overall, extramedullary toxicity and the nonrelapse mortality rate at 2 years (20%) were low and did not increase with dose. Cumulative incidence of relapse/progression reached 31%. The overall survival and progression-free survival rates were 64% and 49%, respectively, in the total study population. An inverse dose dependency of relapse incidence was indicated in the subgroup receiving transplantations from matched related donors (P = .0568).


CONCLUSIONS
Treosulfan-based conditioning was feasible at all three doses. The 3 x 14 g/m(2) dose was selected for additional studies, because it combines desired characteristics of low toxicity and a low relapse rate.
Casper
Jochen
J
University of Rostock, Rostock, Germany. casper.jochen@klinikum-oldenburg.de
Wolff
Daniel
D
Knauf
Wolfgang
W
Blau
Igor W
IW
Ruutu
Tapani
T
Volin
Liisa
L
Wandt
Hannes
H
Schäfer-Eckart
Kerstin
K
Holowiecki
Jerzy
J
Giebel
Sebastian
S
Aschan
Johan
J
Zander
Axel R
AR
Kröger
Nicolaus
N
Hilgendorf
Inken
I
Baumgart
Joachim
J
Mylius
Heidrun A
HA
Pichlmeier
Uwe
U
Freund
Mathias
M
D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine