Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Peter Dreger1,*,
  2. Hartmut Döhner2,
  3. Matthias Ritgen3,
  4. Sebastian Böttcher3,
  5. Raymonde Busch4,
  6. Sascha Dietrich1,
  7. Donald Bunjes2,
  8. Sandra Cohen5,
  9. Jörg Schubert6,
  10. Ute Hegenbart1,
  11. Dietrich Beelen7,
  12. Matthias Zeis8,
  13. Michael Stadler9,
  14. Justin Hasenkamp10,
  15. Lutz Uharek11,
  16. Christof Scheid12,
  17. Andreas Humpe3,
  18. Thorsten Zenz2,
  19. Dirk Winkler2,
  20. Michael Hallek12,
  21. Michael Kneba3,
  22. Norbert Schmitz8, and
  23. Stephan Stilgenbauer2
  1. 1 Department of Medicine V, University of Heidelberg, Heidelberg, Germany;
  2. 2 Department of Medicine III, University of Ulm, Ulm, Germany;
  3. 3 Department of Medicine II, University of Schleswig-Holstein, Kiel, Germany;
  4. 4 Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany;
  5. 5 Hopital Maisonneuve Rosemont, Montreal, Quebec, Canada;
  6. 6 Department of Medicine I, University of Saarland, Homburg, Germany;
  7. 7 Department of Bone Marrow Transplantation, University of Essen, Essen, Germany;
  8. 8 Department of Hematology and Stem Cell Transplantation, Asklepios Klinik St. Georg, Hamburg, Germany;
  9. 9 Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;
  10. 10 Department of Hematology and Oncology, University of Goettingen, Goettingen, Germany;
  11. 11 Department of Medicine III, Charite Campus Benjamin Franklin, Universitaetsmedizin Berlin, Berlin, Germany;
  12. 12 Department of Medicine I, Center for Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany
  1. * Corresponding author; email: peter.dreger{at}med.uni-heidelberg.de

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.