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December 2002, Volume 16, Number 12, Pages 2358-2365
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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)
B Wassmann1, H Pfeifer1, U Scheuring1, S A Klein1, N Gökbuget1, A Binckebanck1, H Martin1, H Gschaidmeier2, D Hoelzer1 and O G Ottmann1

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

2Novartis Pharma AG, Nürnberg, Germany

Correspondence to: O G Ottmann, Medizinische Klinik III, Abteilung für Hämatologie und Onkologie, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany

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.

Leukemia (2002) 16, 2358-2365. doi:10.1038/sj.leu.2402770

Keywords

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL); BCR-ABL; tyrosine kinase; imatinib mesylate (Glivec); allogeneic stem cell transplantation

Received 24 May 2002; accepted 21 August 2002
December 2002, Volume 16, Number 12, Pages 2358-2365
Table of contents    Previous  Abstract  Next   Full text  PDF
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