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Acute Leukemias

Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR–ABL1-positive acute lymphoblastic leukemia

Leukemia volume 27, pages 1254–1262 (2013)Cite this article

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Abstract

Minimal residual disease (MRD) after allogeneic stem cell transplantation (SCT) for Ph+ acute lymphoblastic leukemia (ALL) is predictive of relapse. Imatinib administration subsequent to SCT may prevent relapse, but the role of scheduling and its impact on outcome are not known. In a prospective, randomized multicenter trial, we compared the tolerability and efficacy of post-transplant imatinib administered either prophylactically (arm A; n=26) or following detection of MRD (arm B; n=29). Prophylactic imatinib significantly reduced the incidence of molecular recurrence after SCT compared with MRD-triggered imatinib (40% vs 69%; P=0.046). Median duration of PCR negativity was 26.5 and 6.8 months, respectively (P=0.065). Five-year survival in both interventional groups was high (80 and 74.5%), despite premature discontinuation of imatinib in the majority of patients because of poor tolerability. Relapse probability was significantly higher in patients who became MRD positive (P=0.017). In conclusion, post-transplant imatinib results in a low relapse rate, durable remissions and excellent long-term outcome in patients with BCR–ABL1-positive ALL irrespective of whether it is given prophylactically or MRD-triggered. Reappearance of BCR–ABL1 transcripts early after SCT or at higher levels identifies a small subset of patients who do not benefit sufficiently from imatinib, and in whom alternative approaches should be explored.

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Acknowledgements

We are also indebted to Christine Wabbels and Ann-Katrin Hoeck for data management and to Doreen Badowski, Brigitte Gehrke, Tamara Klan, Gabriele Lippok, Luisa Göller, Sandra Markovic, Anne Zentgraf for their excellent technical assistance. This work was supported by the Deutsche Jose-Carreras Leukämiestiftung (project R06/25), the Adolf-Messer Foundation and by a grant from Novartis. OGO hold an endowed professorship of the Deutsche Jose Carreras Leukämie Stiftung.

Author contributions

HP, BW, DH and OGO conceived and designed the study; HP, BW, WB, JD, MB, M Stadler., DB, VV, TB, M Stelljes, CF, PD, AK, KS-E, RS, EL, BK, HAH, MG, PB, HS, NG, DH and OGO provided study materials or patients; HP, BW, DH and OGO analyzed data; HP and OGO wrote the manuscript; and all authors gave final approval of the manuscript.

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Authors and Affiliations

  1. Department of Hematology/Oncology of the University Hospitals, Frankfurt, Germany

    H Pfeifer, B Wassmann, P Brück, H Serve, D Hoelzer, N Gökbuget & O G Ottmann

  2. Department of Hematology/Oncology of the University Hospitals, Tübingen, Germany

    W Bethge & C Faul

  3. Department of Hematology/Oncology of the University Hospitals, Heidelberg, Germany

    J Dengler & P Dreger

  4. Department of Hematology/Oncology of the University Hospitals, Dresden, Germany

    M Bornhäuser & A Kiani

  5. Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

    M Stadler

  6. Department of Bone Marrow Transplantation, Westdeutsches Tumorzentrum, Universitätsklinikum Essen, Essen, Germany

    D Beelen

  7. Department of Hematology/Oncology of the University Hospitals, Leipzig, Germany

    V Vucinic

  8. Department of Hematology/Oncology of the University Hospitals, Berlin, Germany

    T Burmeister

  9. Department of Hematology/Oncology of the University Hospitals, Münster, Germany

    M Stelljes

  10. Department of Bone Marrow Transplantation, Medizinische Klinik 5 des Klinikum Nürnberg Nord, Nürnberg, Germany

    K Schäfer-Eckart

  11. Deutsche Klinik für Diagnostik, Wiesbaden, Germany

    R Schwerdtfeger

  12. Evangelisches Krankenhaus Hamm, Germany

    E Lange

  13. Department of Hematology and Oncology, Universitätsklinikum des Saarlandes, Homburg Saar, Germany

    B Kubuschok

  14. Medizinische Klinik und Poliklinik, Uni-Klinikum Campus Kiel II, Kiel, Germany

    H A Horst

  15. Sektion Stammzell und Immuntherapie im Dr Mildred-Scheel-Haus, Klinik für Innere Medizin I, Uni-Klinikum Campus Kiel, Kiel, Germany

    M Gramatzki

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  1. H Pfeifer
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on behalf of the GMALL Study Group

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Correspondence to O G Ottmann.

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Competing interests

OGO received honoraria for participation in advisory boards and as speaker at scientific meetings from Novartis. HP received travel support from Novartis. The remaining authors declare no conflict of interest.

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Pfeifer, H., Wassmann, B., Bethge, W. et al. Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR–ABL1-positive acute lymphoblastic leukemia. Leukemia 27, 1254–1262 (2013). https://doi.org/10.1038/leu.2012.352

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