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Evidence of a Graft-Versus-Leukemia Effect in Chronic Lymphocytic Leukemia After Reduced-Intensity Conditioning and Allogeneic Stem-Cell Transplantation: The Cooperative German Transplant Study Group

J. Schetelig, C. Thiede, M. Bornhäuser, R. Schwerdtfeger, M. Kiehl, J. Beyer, H.G. Sayer, N. Kröger, M. Hensel, C. Scheffold, T.K. Held, K. Höffken, A.D. Ho, J. Kienast, A. Neubauer, A.R. Zander, A.A. Fauser, G. Ehninger, W. Siegert

From the Charité Campus Virchow Klinikum and Klinik für Innere Medizin m.S. Hämatologie und Onkologie; Charité Campus Mitte, Humboldt-Universität zu Berlin, Medizinische Klinik II m.S. Onkologie und Hämatologie, Berlin; Universitätsklinikum Carl Gustav Carus, Medizinische Klinik und Poliklinik I, Dresden; Stiftung Deutsche Klinik für Diagnostik GmbH, Zentrum für Blutstammzell-und Knochenmarktransplantation, Wiesbaden; Klinik für Knochenmark-transplantation und Hämatologie/Onkologie GmbH, Idar-Oberstein; Klinikum der Philipps-Universität, Abteilung für Innere Medizin Hämatologie/Onkologie/Immunologie, Marburg; Friedrich Schiller Universität Jena, Klinik für Innere Medizin II; Universitäts-Krankenhaus Eppendorf, Medizinische Klinik Knochenmarktransplantation, Hamburg; Universität Heidelberg, Medizinische Klinik und Poliklinik, Abteilung Innere Medizin V, Hämatologie, Onkologie und Rheumatologie; and Westfälische Wilhelms-Universität, Medizinische Klinik, Innere Medizin A, Münster, Germany.

Address reprint requests to Wolfgang Siegert, MD, Medizinische KIinik II mit Schwerpunkt Onkologie und Hämatologie, Charité Campus Charité Mitte, Schumannstr. 20–21, 10117 Berlin, Germany; email: wolfgang.siegert{at}charite.de.

Purpose: To study whether hematopoietic stem-cell transplantation (HSCT) after reduced-intensity conditioning is effective and tolerable in patients with advanced chronic lymphocytic leukemia (CLL).

Patients and Methods: Thirty patients with advanced B-cell CLL were included into the study. After reduced-intensity conditioning with fludarabine, busulfan, and antithymocyte globulin, patients received a transplant from related (n = 15) or unrelated donors (n = 15). Minimal residual disease (MRD) was monitored with a clone-specific polymerase chain reaction.

Results: After a median follow-up of 2 years, 23 patients are alive (to date). Neutrophil and platelet engraftment occurred after a median of 17.5 and 15 days, respectively. Acute graft-versus-host disease (GVHD) grade 2 to 4 was observed in 17 patients (56%), and chronic GVHD was observed in 21 patients (75%). Twelve patients (40%) achieved a complete remission (CR), and 16 patients (53%) achieved a partial remission. Late CR occurred up to 2 years after transplantation. MRD was monitored in eight patients with CR. All patients achieved a molecular CR. At last follow-up, six patients were in ongoing molecular CR. Causes of death were treatment-related complications in four patients and progressive disease in three patients. The probability of overall survival, progression-free survival, and nonrelapse mortality at 2 years was 72% (95% confidence interval [CI], 54% to 90%), 67% (95% CI, 49% to 85%), and 15% (95% CI, 1% to 29%), respectively.

Conclusion: Treatment-related mortality after reduced-intensity conditioning followed by allogeneic HSCT was low. The procedure induced molecular remissions in patients with advanced CLL. The observation of late remissions provided evidence of a graft-versus-leukemia effect.

Supported by the Deutsche Krebshilfe (70-2755; C.T.,M.B.).

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