Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group 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, German CLL Study Group, Lutz Uharek, Dietrich Beelen, Bertram Glass, Norbert Schmitz, Bernd Hertenstein, Michael Stadler, Matthias Eder, Peter Dreger, Ute Hegenbart, Jörg Schubert, Nadežda Basara, Martin Gramatzki, Michael Kneba, Michael Hallek, Christof Scheid, Andreas Burchert, Sandra Cohen, Dietger Niederwieser, Ernst Holler, Donald Bunjes, Stephan Stilgenbauer, Hartmut Döhner, 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, German CLL Study Group, Lutz Uharek, Dietrich Beelen, Bertram Glass, Norbert Schmitz, Bernd Hertenstein, Michael Stadler, Matthias Eder, Peter Dreger, Ute Hegenbart, Jörg Schubert, Nadežda Basara, Martin Gramatzki, Michael Kneba, Michael Hallek, Christof Scheid, Andreas Burchert, Sandra Cohen, Dietger Niederwieser, Ernst Holler, Donald Bunjes, Stephan Stilgenbauer, Hartmut Döhner
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. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (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 (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at https://ichgcp.net/clinical-trials-registry/NCT00281983" title="See in ClinicalTrials.gov">NCT00281983.
Source: PubMed