The purpose of this prospective multicenter phase-2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia (CLL). Conditioning was based on fludarabine and cyclophosphamide. Longitudinal quantitative monitoring of minimal residual disease (MRD) was done centrally by MRD-flow or RQ-PCR. One-hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 (7-102) months, 4-year non-relapse mortality, event-free survival (EFS) and overall survival (OS) was 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD-negative at 12 months post transplant. Four-year EFS of this subset was 89% with all event-free patients except for two being MRD-negative at the most recent assessment. EFS was similar for all genetic subsets including 17p-. In multivariate analyses, uncontrolled disease at alloSCT and in-vivo T cell depletion with alemtuzumab, but not 17p-, previous purine analogue refractoriness, or donor source (HLA-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk CLL can result in long-term MRD-negative survival in up to half of the patients independent of the underlying genomic risk profile. This trial has been registered at http://clinicaltrials.gov as NCT00281983.
- Submitted March 17, 2010.
- Accepted May 13, 2010.
- Copyright © 2005 American Society of Hematology