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Conditioning Regimens

Reduced-intensity conditioning with fludarabine and thiotepa for second allogeneic transplantation of relapsed patients with AML

Abstract

A second allograft was offered to 58 relapsed AML patients after conditioning with fludarabine 90–150 mg/m2 and thiotepa 15 mg/kg, in most cases with active disease. Median age was 53 years (range 23–69), median time to relapse after the first allo-SCT was 326 (47–2189) days and median follow-up was 6.7 years. GVHD prophylaxis consisted mainly of CsA and alemtuzumab. Response rates at 1 month were CR in 50 and persistent disease in 3/53 evaluable patients. At 3 years, the relapse incidence (95% confidence interval) was 56 (45–71)%, the TRM 31 (21–46)%, the OS rate was 18 (9–29)% and the EFS rate was 13 (5–23)%. OS improved with younger patient age, longer relapse-free interval after the first allo-SCT and the development of chronic GVHD. Patients 65 years old who relapsed >12 months after the first allograft (n=20) had a 3-year OS rate of 41 (19–62)%. Conventional cytogenetics and FLT3 mutation status did not affect outcome. Our regimen is feasible and provides at least for a subgroup of patients with AML recurrence after allo-SCT a reasonable therapeutic option in an otherwise fatal situation. Further modifications and a better understanding of the underlying biology could help lower the risk of relapse.

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Acknowledgements

We acknowledge the contributions of E Lenartz and P Isele-Hiss in donor search and coordination, I Matt in data management, E Samek, S Enger and I Huber for technical assistance in the laboratory, C Cürten for proofreading the manuscript and R Mertelsmann for continuous support. We thank M Bentz, J Mezger, F Hirsch, A Jakob and W Brugger for patient referral and the nurses and fellows of ward Löhr for their dedication to the patients.

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Correspondence to J Finke.

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Christopoulos, P., Schmoor, C., Waterhouse, M. et al. Reduced-intensity conditioning with fludarabine and thiotepa for second allogeneic transplantation of relapsed patients with AML. Bone Marrow Transplant 48, 901–907 (2013). https://doi.org/10.1038/bmt.2012.267

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