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Chronic Leukemia

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

Bone Marrow Transplantation volume 50, pages 1279–1285 (2015)Cite this article

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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.

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Authors and Affiliations

  1. Department Medicine V, University of Heidelberg, Heidelberg, Germany

    M Hahn, S Dietrich, U Hegenbart, M Rieger, P Stadtherr, A Bondong, R Schulz, T Schmitt, I Herth, T Luft, S Schönland, M Witzens-Harig, T Zenz, A D Ho & P Dreger

  2. Department Medicine II, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany

    S Böttcher, M Ritgen & M Kneba

  3. Praxis für Hämatologie und Onkologie, Darmstadt, Germany

    M Rieger

  4. Transplantation Immunology, University of Heidelberg, Heidelberg, Germany

    T H Tran

  5. Städtisches Klinikum and Onkologische Praxis, Bielefeld, Germany

    M Görner

  6. Department of Translational Oncology, National Center for Tumor Diseases (NCT), University of Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany

    T Zenz

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  1. M Hahn
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Corresponding author

Correspondence to M Hahn.

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Competing interests

PD is Board member of the European Group for Blood and Marrow Transplantation (EBMT) and the German Working Group for Marrow and Blood Stem Cell Transplantation (DAG-KBT); has been working as Consultant for Chugai Pharma and Riemser Pharma; has worked on Advisory Boards for Janssen and Gilead; and has received honoraria from Gilead, Glaxo Smith Kline, Janssen, Mundipharma and Riemser Pharma. MH has received research support from Riemser Pharma. IH has received research support from Medac GmbH and Roche Pharma. SB received research support from Roche, AbbVie and Celgene and honoraria from Roche and AbbVie, and has been working as Consultant for Roche. The remaining authors declare no conflicts of interest.

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Hahn, M., Böttcher, S., Dietrich, S. et al. Allogeneic hematopoietic stem cell transplantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse. Bone Marrow Transplant 50, 1279–1285 (2015). https://doi.org/10.1038/bmt.2015.150

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