Background and 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 intensity and efficacy might 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.
Patients and 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 (3x10, 3x12 or 3x14g/m2 i.v.) and fludarabine (5x30mg/m2 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.
After a median follow up of 3.2 years an actuarial overall survival (OS) of 59.2 % (at 3 years) and an event-free survival (EFS) of 40,1% has been reached. Patients with related donor or transplantation in CR had a better OS (85,4 resp. 74,2%) and EFS (52,2% resp. 61,9%). The cumulative incidence of relapse at 3 years was 26,2%. Transplantation in CR resulted in a lower relapse incidence than transplantation not in CR (17,9 vs. 30%). Treatment-related mortality (TRM) at day 100 is 17,4% (cumulative incidence). In stepwise Cox regression analyses for OS, EFS and TRM only the covariables transplantation in CR vs. not in CR and the donor status were shown to be influential. No effects were detected for age (under 50 years vs. 50 years and older), concomitant disease (present vs. not present) or intensity of pretreatment.
The cumulative incidence for acute graft-versus-host disease (GvHD) °I-IV at day 100 was 43.3%. The cumulative incidence for chronic GvHD at 3 years is 36.1%.
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.