Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Magina, N.
Conventional post-remission therapy in adult acute myeloid leukemia – a systematic review / meta-analysis
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2016. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Berghold Andrea
- Sill Heinz
- Altmetrics:
- Abstract:
- Background: Acute myeloid leukemia (AML) is a heterogenous malignancy caused by transformation of hematopoietic stem and precursor cells. Current therapies applied with curative intention consist of induction using cytarabine and anthracycline followed by post-remission treatment. The latter can be either allogeneic stem cell transplantation (HSCT) or conventional consolidation chemotherapy according to leukemia and patient-related factors. However, the question of the optimal cytarabine dose and number of treatment cycles remains open. This systematic review and meta-analysis aims to investigate the comparison of the different doses of cytarabine (high / intermediate / low), the optimal number of consolidation cycles and whether mono- or combination therapy is of advantage with respect to younger patients (=65 years) and elderly patients (>65 years). Methods: To investigate this research question, a systematic review including a meta-analysis was performed according to the PRISMA Statement. The databases of Pubmed and Cochrane Library from 1990 to 2014 as well as the archives of the American Society of Hematology and the NCCN guidelines for AML were screened. Original articles reporting randomized clinical trials that at least included 100 patients undergoing conventional consolidation therapy were identified. Relevant data were extracted, described and processed by a meta-analysis. Results: Of 38,814 potentially relevant articles, 18 were finally included in this systematic review fulfilling our inclusion critera reporting on a total of 14,572 patients with AML. Fifteen matched to the primary goal of the systematic review and meta-analysis of patients aged 65 years and younger. The comparison of low/intermediate versus high dose cytarabine indicated that disease free survival (DFS) may be improved by high dose administration (HR 0.90 [0.80; 1.02]) but was less pronounced for overall survival (OS) (HR 0.96 [0.87; 1.06]). Our results did not show any significant differences between long term and short term therapy with respect to OS (HR 1.06 [0.89; 1.25]) either, but there was a significant result that less cycles may lead to worse DFS (HR 1.16 [1.03; 1.29]). Evaluating whether monotherapy or combination therapy is of advantage, no significant results could be found for both, DFS (HR 1.02 [0.93; 1.11]) and OS (HR 1.08 [0.97; 1.20]). Conclusion: This systematic review and meta-analysis demonstrate that high dose cytarabine may improve DFS but not OS used as conventional consolidation treatment for patients with AML.. Concerning the number of cycles, we could show that an increased number of consolidation chemotherapy cycles enhance DFS but not OS. There was no benefit in adding other chemotherapy drugs to the cytarabine treatment schedule. Further work will focus on assessing these parameters in certain AML subgroups, most importantly those based on cytogenetic aberrations.