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

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, ra...

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Main Authors: Pfeifer, Heike (Author) , Wassmann, B. (Author) , Bethge, W. (Author) , Dengler, Jolanta (Author) , Bornhäuser, M. (Author) , Stadler, M. (Author) , Beelen, D. (Author) , Vucinic, V. (Author) , Burmeister, T. (Author) , Stelljes, M. (Author) , Faul, C. (Author) , Dreger, Peter (Author) , Kiani, A. (Author) , Schäfer-Eckart, K. (Author) , Schwerdtfeger, R. (Author) , Lange, E. (Author) , Kubuschok, B. (Author) , Horst, H. A. (Author) , Gramatzki, M. (Author) , Brück, P. (Author) , Serve, H. (Author) , Hoelzer, D. (Author) , Gökbuget, N. (Author) , Ottmann, O. G. (Author)
Format: Article (Journal)
Language:English
Published: 30 April 2013
In: Leukemia
Year: 2013, Volume: 27, Issue: 6, Pages: 1254-1262
ISSN:1476-5551
DOI:10.1038/leu.2012.352
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/leu.2012.352
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/leu2012352
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Author Notes:H. Pfeifer, B. Wassmann, W. Bethge, J. Dengler, M. Bornhäuser, M. Stadler, D. Beelen, V. Vucinic, T. Burmeister, M. Stelljes, C. Faul, P. Dreger, A. Kiani, K. Schäfer-Eckart, R. Schwerdtfeger, E. Lange, B. Kubuschok, H.A. Horst, M. Gramatzki, P. Brück, H. Serve, D. Hoelzer, N. Gökbuget and O.G. Ottmann

MARC

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520 |a 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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