Abstract
In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term disease control can only be achieved by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the safety and efficacy of clofarabine-based salvage therapy. The study was designed as phase II, multicenter, intent-to-transplant (ITT) study. A total of 84 patients with r/r AML were enrolled. All patients received at least one cycle of CLARA (clofarabine 30 mg/m2 and cytarabine 1 g/m2, days 1–5). Chemo-responsive patients with a donor received HSCT in aplasia after first CLARA. Generally, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine (4 × 30 mg/m2) and melphalan (140 mg/m2). The median patient age was 61 years (range 40–75). On day 15 after start of CLARA, 26% of patients were in a morphologically leukemia-free state and 79% exposed a reduction in bone marrow blasts. Overall, 67% of the patients received HSCT within the trial. The primary end point, defined as complete remission after HSCT, was achieved by 60% of the patients. According to the ITT, overall survival at 2 years was 43% (95% confidence interval (CI), 32–54%). The 2-year disease-free survival for transplanted patients was 52% (95% CI, 40–69%). Clofarabine-based salvage therapy combined with allogeneic HSCT in aplasia shows promising results in patients with r/r AML.
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Consultant or advisory role: Johannes Schetelig and Jan Moritz Middeke: Sanofi. The other authors declare no conflict of interest.
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Conception and design: Johannes Schetelig; administrative support: Martin Bornhäuser, Gerhard Ehninger; provision of study materials or patients: Jan Moritz Middeke, Regina Herbst, Stefani Parmentier, Gesine Bug, Mathias Hänel, Gernot Stuhler, Kerstin Schäfer-Eckart, Wolf Rösler, Stefan Klein, Wolfgang Bethge, Ulrich Bitz, Bozena Büttner, Holger Knoth, Nael Alakel, Markus Schaich, Anke Morgner, Michael Kramer, Katja Sockel, Malte von Bonin, Friedrich Stölzel, Uwe Platzbecker, Christoph Röllig, Martin Bornhäuser; collection and assembly of data: Johannes Schetelig, Michael Kramer, Jan Moritz Middeke; data analysis and interpretation: Johannes Schetelig, Michael Kramer, Martin Bornhäuser, Jan Moritz Middeke; manuscript writing: all authors; final approval of manuscript: all authors.
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Middeke, J., Herbst, R., Parmentier, S. et al. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia 30, 261–267 (2016). https://doi.org/10.1038/leu.2015.226
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DOI: https://doi.org/10.1038/leu.2015.226
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