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Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the GCLLSG CLL3X trial

Peter Dreger, Hartmut Döhner, Matthias Ritgen, Sebastian Böttcher, Raymonde Busch, Sascha Dietrich, Donald Bunjes, Sandra Cohen, Jörg Schubert, Ute Hegenbart, Dietrich Beelen, Matthias Zeis, Michael Stadler, Justin Hasenkamp, Lutz Uharek, Christof Scheid, Andreas Humpe, Thorsten Zenz, Dirk Winkler, Michael Hallek, Michael Kneba, Norbert Schmitz, Stephan Stilgenbauer

Abstract

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.