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Reduced intensity conditioning regimens including alkylating chemotherapy do not alter survival outcomes after allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia compared to low-intensity non-myeloablative conditioning

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

The optimal dose intensity for conditioning prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) for chronic lymphocytic leukemia (CLL) is unknown.

Methods

We retrospectively compared outcomes of patients who received a first alloHCST after non-myeloablative (NMA) and reduced intensity conditioning (RIC). Data of 432 patients with a median age of 55 years were included, of which 86 patients underwent NMA and 346 RIC.

Results

The median follow-up after alloHSCT was 4.3 years. Compared to the RIC group, more NMA patients had purine-analog-sensitive disease, were in complete remission and received matched related donor transplantation. After RIC, the probabilities for 5-year OS, EFS, CIR, and NRM were 46%, 38%, 28%, and 35% and after NMA the respective probabilities were 52%, 43%, 25%, and 32%. In multivariate analysis, remission status prior to conditioning but not RIC versus NMA conditioning had a significant impact on CIR, EFS, and OS.

Conclusion

Presumed higher anti-leukemic activity of RIC versus NMA conditioning did not translate into better outcomes after alloHSCT, but better remission status prior to conditioning did. Effective pathway inhibitor-based salvage therapies combined with NMA conditioning might thus represent the most attractive contemporary approach for alloHSCT for patients with CLL.

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Acknowledgements

We are grateful to the data managers of the contributing centers and the staff of the EBMT data office in Leiden especially Anja Henseler, Annelies Kleijne, and Anja van Biezen who provided high-level support at all stages of the CLL data quality initiative and therefore enabled the success of this initiative. Further, we thank Christian Klesse who significantly contributed to the data management and the statistical analyses.

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Authors and Affiliations

  1. BMT Unit Department of Hematology, Rigshospitalet, Copenhagen, Denmark

    Niels Smedegaard Andersen

  2. Medical Department I, University Hospital Dresden, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany

    Martin Bornhäuser & Johannes Schetelig

  3. DKMS gGmbH, Dresden, Germany

    Martin Bornhäuser & Johannes Schetelig

  4. Division of Stem Cell Transplantation and Immunotherapy, University Hospital Schleswig-Holstein, Kiel, Germany

    Martin Gramatzki

  5. Medizinische Klinik u. Poliklinik V, University of Heidelberg, Heidelberg, Germany

    Peter Dreger & Stefan Schönland

  6. Department of Haematology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    Antonin Vitek

  7. Department of Hematology/Oncology, Charles University Hospital, Pilsen, Czech Republic

    Michal Karas

  8. Centre Hospitalier Lyon-Sud-Hématologie, Lyon, France

    Mauricette Michallet

  9. Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Carol Moreno

  10. Department of Internal Medicine Hematology, University Hospital Maastricht, Maastricht, The Netherlands

    Michel van Gelder

  11. Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands

    Anja Henseler & Liesbeth C. de Wreede

  12. Bone Marrow Transplantation Centre, University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

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  1. Niels Smedegaard Andersen
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  2. Martin Bornhäuser
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  8. Carol Moreno
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  9. Michel van Gelder
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  12. Stefan Schönland
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  13. Nicolaus Kröger
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  14. Johannes Schetelig
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the CLL subcommittee, Chronic Malignancies Working Party

Corresponding author

Correspondence to Johannes Schetelig.

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The authors declare to have no conflict of interest with the issue addressed with this manuscript.

Ethical approval

This is a retrospective registry study of the European Society of Blood and Marrow Transplantation (EBMT). Patients were not exposed to study procedures or addional assessments. The study was approved by the internal study board of the Chronic Malignancies Working Party of EBMT. EBMT Registry data were analyzed in full compliance with the Society’s institutional standards. All patients have consented in the use of their medical data to advance hematopoietic cell transplantation.

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Andersen, N.S., Bornhäuser, M., Gramatzki, M. et al. Reduced intensity conditioning regimens including alkylating chemotherapy do not alter survival outcomes after allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia compared to low-intensity non-myeloablative conditioning. J Cancer Res Clin Oncol 145, 2823–2834 (2019). https://doi.org/10.1007/s00432-019-03014-x

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