title: Allogeneic hematopoietic stem cell transplantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse.
abstract: 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.
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hahn
authors.affiliation: Department Medicine II, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Böttcher
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dietrich
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Hegenbart
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.|Praxis für Hämatologie und Onkologie, Darmstadt, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rieger
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Stadtherr
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Bondong
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schulz
authors.affiliation: Department Medicine II, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ritgen
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schmitt
authors.affiliation: Transplantation Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: T H
authors.initials: TH
authors.lastname: Tran
authors.affiliation: Städtisches Klinikum and Onkologische Praxis, Bielefeld, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Görner
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Herth
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Luft
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schönland
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Witzens-Harig
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.|Department of Translational Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Zenz
authors.affiliation: Department Medicine II, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kneba
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: A D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Dreger
mesh_terms: D000328:Adult; D000368:Aged; D060740:Disease Eradication; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012008:Recurrence; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome