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Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning

Leukemia volume 17, pages 841–848 (2003)Cite this article

Abstract

Allogeneic stem cell transplantation (SCT) using reduced-intensity conditioning (RIC) has potential to be a promising treatment of aggressive chronic lymphocytic leukemia (CLL). Since available clinical data obtained with this novel approach are very limited, we have performed a survey on this issue. Data of 77 patients were collected from 29 European Group for Blood and Marrow Transplantation centers. Median age was 54 (30–66) years, and the median number of previous chemotherapy regimens was 3 (0–8). HLA-identical sibling donors were used in 81% of the cases. Moderate conditioning regimens (mainly low-dose total body irradiation (TBI) or fludarabine–cyclophosphamide combinations) were administered to 56% of the patients, whereas the remainder received more intense conditioning consisting of fludarabine–busulfan or high-dose melphalan combinations. In 40% of the patients, in vivo T-cell depletion (TCD) with anti-thymocyte globulin or CAMPATH-1H was part of the conditioning regimen. Cumulative treatment-related mortality (TRM) was 18% (95% CI 9; 27) after 12 months. Complete chimerism as well as best response was not achieved immediately post-transplant but took a median of 3 months to develop. The 2-year probability of relapse was 31% (95% CI 18; 44), with no event occurring later than 12 months post transplant in the absence of TCD. With one exception, relapses were not observed after onset of chronic graft-versus-host disease. Event-free and overall survival at 24 months were 56% (95% CI 43; 69) and 72% (95% CI 61; 83), respectively. The median follow-up was 18 (1–44) months. Donor lymphocyte infusions or secondary transplants were performed in 19 patients with insufficient disease control and/or incomplete donor chimerism post-transplant, leading to a response in seven patients (37%). Preliminary multivariate analysis identified less than PR at transplant (hazard ratio (HR) 3.5; P<0.01) and alternative donor (HR 3.1; P=0.02) as significant risk factors for relapse, whereas number of previous regimens >2 (HR 5.4; P=0.03), TBI (HR 2.5; P=0.05), and alternative donor (HR 2.3; P=0.08) were risk factors for survival. We conclude that RIC might favorably influence the outcome after allogeneic SCT for CLL by reducing TRM while preserving graft-versus leukemia activity.

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Acknowledgements

We thank Rosi Schiefelbein for excellent secretary assistance. Supported by the Deutsche José Carreras Leukämie-Stiftung (Grants DJCLS-R16).

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Authors and Affiliations

  1. Department of Hematology, Allgemeines Krankenhaus St Georg, Hamburg, Germany

    P Dreger

  2. Department of Medical Statistics, University Medical Centre, Leiden, The Netherlands

    R Brand & A van Biezen

  3. Department of Hematology, University of Medical Sciences, Poznan, Poland

    J Hansz

  4. Department of Haematology, Heartlands Hospital, Birmingham, UK

    D Milligan

  5. Bone Marrow Transplantation Unit, Istituto Nazionale dei Tumori, University of Milano, Italy

    P Corradini

  6. Department of Haematology and Oncology, University of Freiburg, Germany

    J Finke

  7. BMT Center, Ospedale Maggiore, Milano, Italy

    G L Deliliers

  8. Servicio de Hematologica Clinica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    R Martino

  9. Haematology Department, Nottingham City Hospital, Nottingham, UK

    N Russell

  10. Unite de Greffe de Cellules Souches Hématopoïétiques, Hôpital Edouard Herriot, Lyon, France

    M Michallet

  11. Department of Hematology and Medical Oncology, University of Leipzig, Germany

    D Niederwieser

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Dreger, P., Brand, R., Hansz, J. et al. Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning. Leukemia 17, 841–848 (2003). https://doi.org/10.1038/sj.leu.2402905

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