[Allogeneic blood stem cell transplantation in high-risk patients after conditioning with treosulfan and fludarabine].
OBJECTIVE
Allogeneic transplantation can not be offered to many patients due to potential side-effects of conventional conditioning. Dose-reduced conditioning approaches improve tolerability, however, treatment efficacy may be reduced as well. We have, therefore, developed a dose intense but toxicity reduced conditioning regimen based on treosulfan and fludarabine and report first results.


METHODS
65 patients with a median age of 50 years were transplanted from related (n = 21) or unrelated donors (n = 44) after conditioning with treosulfan (3 x 10, 3 x 12 or 3 x 14 g/m(2) i. v.) and fludarabine (5 x 30 mg/m(2) i. v.). 21 patients were in complete remission (CR) and 44 patients had not reached a CR at the time of transplantation. 59 of 65 patients were considered unfit for a conventional conditioning regimen.


RESULTS
The actuarial overall survival after 3 years is 59.2 %, the event-free survival 40.1 %. Patients with a related donor or transplantation in CR had a better overall (85.4 resp. 74.2 %) and event-free survival (52.2 % resp. 61.9 %). The cumulative incidence of relapse at 3 years was 26.2 %. Non-relapse mortality at day 100 is 17.4 % (cumulative incidence). In stepwise Cox regression analyses for overall survival, event-free survival and non-relapse mortality the covariables transplantation in CR vs. not in CR and the donor status were shown to be influential.


CONCLUSIONS
These results with a conditioning therapy of treosulfan and fludarabine indicate that patients despite higher age, concomitant disease or after intensive pretreatment can be successfully transplanted without increased treatment-related mortality.
Casper
J
J
Abteilung Hämatologie und Onkologie der Medizinischen Fakultät der Universität Rostock. jochen.casper@med.uni-rostock.de
Wilhelm
S
S
Steiner
B
B
Wolff
D
D
Grobe
N
N
Hähling
D
D
Hartung
G
G
Hilgendorf
I
I
Lück
A
A
Junghanss
C
C
Kahl
C
C
Baumgart
J
J
Pichlmeier
U
U
Freund
M
M
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality / Q000592:standards; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012044:Regression Analysis; D012074:Remission Induction; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality / Q000592:standards; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine