Reassessing the role of high dose cytarabine and mitoxantrone in relapsed/refractory acute myeloid leukemia
| Autor: | G. Rechavi, Drorit Merkel, Avichai Shimoni, Chen Gefen, Jonathan Canaani, Yulia Volchek, Noga Shem-Tov, Arnon Nagler, Meital Nagar, Ronit Yerushalmi, Abraham Avigdor, Gabriel Heering, Ninette Amariglio |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Oncology
medicine.medical_specialty NPM1 Mitoxantrone FLT3-ITD Myeloid business.industry Myeloid leukemia Salvage therapy acute myeloid leukemia medicine.anatomical_structure Refractory Internal medicine medicine Cytarabine next-generation sequencing business Survival rate Research Paper medicine.drug |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | A substantial segment of patients with acute myeloid leukemia (AML) will relapse following an initial response to induction therapy or will prove to be primary refractory. High-dose cytarabine and mitoxantrone (HiDAC/MITO) is an established salvage therapy for these patients. We studied all adult patients with relapsed/refractory (R/R) AML who were treated with HiDAC/MITO in our center between the years 2008-2017. To determine whether responding patients harbored a unique molecular signature, we performed targeted next-generation sequencing (NGS) on a subset of patients. The study cohort consisted of 172 patients with a median age of 54 years (range 18–77). The composite complete remission rate was 58%; 11 patients (6%) died during salvage therapy. Median survival was 11.4 months with a 1-year survival rate of 48%. In multivariate analysis favorable risk cytogenetics [Odds ratio (OR)=0.34, confidence interval (CI) 95%, 0.17–0.68; P = 0.002], and de-novo AML (OR = 0.4, CI 95%, 0.16–0.98; P = 0.047) were independently associated with a favorable response. Patients who attained a complete remission had a median survival of 43.7 months compared with 5.2 months for refractory patients (p < 0.0001). Neither the FLT3-ITD and NPM1 mutational status nor the indication for salvage therapy significantly impacted on the response to HiDAC/MITO salvage. NGS analysis identified 20 different mutations across the myeloid gene spectrum with a distinct TP53 signature detected in non-responding patients. HiDAC/MITO is an effective salvage regimen in R/R AML, however patients with adverse cytogenetics or secondary disease may not benefit as much from this approach. |
| Databáze: | OpenAIRE |
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