Induction Chemotherapy Followed Immediately by Busulfan-Based Reduced Conditioning and Allografting in Elderly Patients with Advanced MDS or sAML.

Allogeneic stem cell transplantation after a dose-reduced conditioning has become a reasonable treatment option for elderly patients with MDS/sAML. For patients with high number of blasts prior transplantation, the risk of relapse is considerably. To reduce the risk of relapse after dose-reduced allograft we performed a study using an anthracycline based induction chemotherapy (amsacrine, cytosine-arabinoside, fludarabine) followed immediately by a reduced intensity conditioning therapy consisting of busulfan (8mg/kg).

Between November 2005 and November 2008, 49 patients with MDS (n = 24), CMML (n = 8) and sAML (n = 17) and a median age of 61 years (r: 26 – 73) and a median number of 13% blasts were included. Stem cell source were unrelated (n = 43) or related donor (n = 6).

No graft failure was observed and the median time to leukocyte engraftment (> 1.0 × 10⁹ /l) was only 10 days (r: 7 – 32). The incidence of acute graft-versus-host disease grade II to IV was 39 % and of grade III / IV was 14 %. Chronic GvHD was noted in 57 % of the patients, which was limited in 35 % and extensive in 32 % of the patients. After a median follow-up of 15 months (r: 3 – 35) the two-years estimated disease-free and overall survival was 49 % (95 % CI 33 – 65 %) and 54 % (95 % CI 39 – 69 %), respectively. The 1 year cumulative incidence of treatment-related mortality was 29 % (95 % CI 15 – 43 %). The 2 year cumulative incidence of relapse was 18 % (95 % CI 6 – 30 %). Patients with fully matched related or unrelated donor had a better survival than patients transplanted from mismatched donor (69 % vs. 37 %; p=0.06).

A sequential approach using anthracycline based induction chemotherapy followed immediately by a busulfan based reduced conditioning regimen and allogeneic stem cell transplantation from related and unrelated donors resulted in a fast engraftment and a relative low risk of relapse in elderly patients with advanced MDS or sAML. To lower the therapy related mortality a careful donor selection is mandatory.

No relevant conflicts of interest to declare.