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Spotlight on IMATINIB as a Model for Signal Transduction Inhibitors

Therapy with imatinib mesylate (Glivec) preceding allogeneic stem cell transplantation (SCT) in relapsed or refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL)

Leukemia volume 16, pages 2358–2365 (2002)Cite this article

Abstract

Imatinib has pronounced antileukemic activity in Ph+ALL, although responses are usually short. To determine whether imatinib may facilitate allogeneic SCT in relapsed or refractory Ph+ALL, we evaluated 46 consecutive, not previously transplanted patients who were enrolled in phase II studies of imatinib. Of 30 patients eligible for SCT, 22 (73%) were actually transplanted. Ten patients were in complete hematologic remission (CHR) (n = 5) or had a complete marrow response (CMR) (n = 5) at the time of SCT, 12 patients had again relapsed or were refractory. After SCT, 18 patients were in complete remission, one patient was refractory, three patients died prior to response assessment. Seven patients (32%) are in ongoing complete remission with a median follow-up of 9.4 (range 1.7–23.8) months. Seven patients (32%) relapsed a median of 5.2 months after SCT. Transplant-related mortality (TRM) was 36%. Probability of disease-free survival (DFS) is 25.5 ± 9.8% overall and 51.4 ± 17.7% when SCT was performed in CHR or CMR, compared with 8.3 ± 8% for SCT during overt leukemia (P = 0.06). In conclusion, imatinib is a well-tolerated salvage therapy prior to allogeneic SCT in patients with Ph+ALL, but requires that SCT be performed within a few weeks of starting treatment to avoid resistance. Disease status at time of transplantation is an important determinant of DFS and TRM.

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Acknowledgements

We are indebted to Brigitte Gehrke, Anja Goodwin, Heike Nürnberger, Martine Pape, and Sandra Wagner for their excellent technical assistance, and to Angelika Spies for study management. We also thank the referring physicians for their excellent cooperation in caring for the patients throughout the study: G Mau, Braunschweig; FK Baur, W Heit, Essen-Werden; HG Höffkes, Fulda; F Ustaoglu, A Ho, Heidelberg; DW Beelen, M Pfreundschuh, Homburg/Saar; D Voliotis, P Staib, Köln; J Beyer, A Neubauer, Marburg; T Lipp, München-Schwabing; M Schleuning, HJ Kolb, München-Grohadern (LMU); M Stelljes, J Kienast, Münster; T Hegge, Osnabrück; J Casper, M Freund, Rostock; D Hähling, Schwerin; L Leimer, W Aulitzky, Stuttgart; C Denzlinger, L Kanz, Tübingen; D Bunjes, H Döhner, Ulm; M Prumbaum, R Schwerdtfeger, Wiesbaden (DKD). Supported by the BMBF, Competence Network Leukemias, grant No. 01GI9971 and by a grant from the Adolf Messer Foundation.

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  1. Abteilung für Hämatologie und Onkologie of the Johann Wolfgang Goethe-Universität, Medizinische Klinik III, Frankfurt, Germany

    B Wassmann, H Pfeifer, U Scheuring, SA Klein, N Gökbuget, A Binckebanck, H Martin, D Hoelzer & OG Ottmann

  2. Novartis Pharma AG, Nürnberg, Germany

    H Gschaidmeier

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Wassmann, B., Pfeifer, H., Scheuring, U. et al. Therapy with imatinib mesylate (Glivec) preceding allogeneic stem cell transplantation (SCT) in relapsed or refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL). Leukemia 16, 2358–2365 (2002). https://doi.org/10.1038/sj.leu.2402770

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