Journal of Cancer Research and Clinical Oncology, 2014, Vol.140(8), pp.1391-1397
Byline: Ulf Schnetzke (1), Peter Fix (3), Baerbel Spies-Weisshart (1), Karin Schrenk (1), Anita Glaser (2), Hans-Joerg Fricke (1), Paul Rosee (1), Andreas Hochhaus (1), Sebastian Scholl (1) Keywords: AML; Relapse; FLT3; Cyclophosphamide; Stem cell transplantation Abstract: Background Approximately, 70 % of adult patients with de novo acute myeloid leukemia (AML) achieve a complete remission (CR) while 10--20 % of AML are refractory to induction chemotherapy. Furthermore, a significant proportion of AML patients in CR will relapse during or after consolidation treatment. There is no evidence for a standard salvage regimen and most centers use a combination of an anthracycline and cytarabine (AraC). The aim of this study was to investigate the impact of two age-adjusted regimens containing AraC and cyclophosphamide applied for the treatment of relapsed or refractory AML. Patients and methods We retrospectively analyzed 60 patients (24 male, 36 female median age 56 years) with relapsed or refractory AML who were treated with a combination of AraC and cyclophosphamide monocentrically between October 2000 and January 2013. Two different protocols containing either high-dose (hAC) or intermediate-dose cytarabin (iAC) have been applied dependent on age and performance status. Results We demonstrate an overall response rate (CR + PR) induced by hAC and iAC of 56.7 %. Importantly, a complete remission rate (CR + CRp) of 52.2 % was found in patients who received the hAC regimen while only 8.8 % of patients achieved a CR following the iAC protocol (p 〈 0.001). The rate of refractory disease was 26.1 and 47.1 %, respectively. High-risk cytogenetics, i.e., a complex aberrant or monosomal karyotype had no effect on achievement of CR after hAC. In addition, there was no impact of activating FLT3 mutations on response to treatment according to the hAC regimen. In the cohort of patients treated with the iAC protocol, treatment-related mortality of 11.8 % within 60 days was observed but none of the patients who received the hAC regimen died within the first 2 months following chemotherapy. The toxicity profile was acceptable at both cytarabine dose levels. Importantly, 19 patients (82.6 %) of the hAC cohort underwent allogeneic hematopoietic stem cell transplantation (HSCT) as consecutive treatment. Conclusion The hAC regimen represents a promising therapeutic approach to induce a second CR in younger patients with relapsed or refractory AML prior to HSCT without using anthracyclines. Author Affiliation: (1) Abteilung Hamatologie und Internistische Onkologie, Klinik fur Innere Medizin II, Universitatsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany (2) Institut fur Humangenetik, Universitatsklinikum Jena, Jena, Germany (3) Abteilung Internistische Onkologie und Hamatologie, Zentralklinik Bad Berka, Bad Berka, Germany Article History: Registration Date: 28/03/2014 Received Date: 12/03/2014 Accepted Date: 28/03/2014 Online Date: 12/04/2014 Article note: Ulf Schnetzke and Peter Fix have contributed equally to this work.
AML ; Relapse ; FLT3 ; Cyclophosphamide ; Stem cell transplantation
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