Allogeneic hematopoietic stem cell transplantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse

To elucidate factors contributing to the effectiveness of allogeneic hematopoietic stem cell transplantation (alloHCT) in high-risk CLL, immune interventions, GvHD and clinical outcome of 77 consecutive patients allografted for CLL were analyzed. Immune modulation (immunosuppression tapering, rituxi...

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Main Authors: Hahn, Michael (Author) , Böttcher, S. (Author) , Dietrich, Sascha (Author) , Hegenbart, Ute (Author) , Rieger, Michael (Author) , Stadtherr, Peter (Author) , Bondong, Andrea (Author) , Ritgen, Matthias (Author) , Schmitt, Thomas (Author) , Tran, Thuong Hien (Author) , Görner, Martin (Author) , Krämer, Isabelle (Author) , Luft, Thomas (Author) , Schönland, Stefan (Author) , Witzens-Harig, Mathias (Author) , Zenz, Thorsten (Author) , Kneba, Michael (Author) , Ho, Anthony Dick (Author) , Dreger, Peter (Author)
Other Authors: Schulz, Renate (Other)
Format: Article (Journal)
Language:English
Published: 6 July 2015
In: Bone marrow transplantation
Year: 2015, Volume: 50, Issue: 10, Pages: 1279-1285
ISSN:1476-5365
DOI:10.1038/bmt.2015.150
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/bmt.2015.150
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/bmt2015150
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Author Notes:M. Hahn, S. Böttcher, S. Dietrich, U. Hegenbart, M. Rieger, P. Stadtherr, A. Bondong, R. Schulz, M. Ritgen, T. Schmitt, T.H. Tran, M. Görner, I. Herth, T. Luft, S. Schönland, M. Witzens-Harig, T. Zenz, M. Kneba, A.D. Ho and P. Dreger

MARC

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520 |a To elucidate factors contributing to the effectiveness of allogeneic hematopoietic stem cell transplantation (alloHCT) in high-risk CLL, immune interventions, GvHD and clinical outcome of 77 consecutive patients allografted for CLL were analyzed. Immune modulation (immunosuppression tapering, rituximab-augmented donor lymphocyte infusions) was guided by minimal residual disease (MRD) monitoring and commenced at a median of 91 (22-273) days after alloHCT, resulting in a probability of being event free and MRD-negative 1 year after transplant of 57% (84% in those encountering chronic GvHD). Patients who were event free and MRD-negative at the 12-month landmark had a 4-year PFS of 77% and largely remained durably MRD-negative if MRD clearance had occurred subsequent to immune modulation. Three-year overall survival, PFS, relapse incidence and non-relapse mortality of all 77 patients were 69, 57, 26 and 24%, respectively. Survival was not affected by EBMT risk category but by active disease at alloHCT, which could not be overcome by intensification of conditioning. Twenty-three patients who experienced relapse post alloHCT had a survival of 56% at 2 years after CLL recurrence. In conclusion, MRD-guided immune modulation after alloHCT for high-risk CLL can provide durable MRD clearance in more than half of the patients. 
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