Abstract

BackgroundCytogenetic abnormalities and mutated genes indicate the role of consolidation therapy with hematopoietic stem cell transplantation (HSCT) or chemotherapy in acute myeloid leukemia (AML). In this study, we conducted a retrospective study in adult AML patients with newly diagnosed with de novo AML who did not undergo HSCT, to study long term relapse free survival (RFS) and overall survival (OS) after consolidation chemotherapy.MethodsWe recruited 141 consecutive AML patients during January 2010–June 2017, the patients received induction chemotherapy with standard dose Ara-C and Idarubicin (7 + 3 or 5 + 2 regimen) followed by intermediate (IDAC) or high dose Ara-c (HiDAC) consolidation therapy.ResultsNormal karyotype, complex, favorable, intermediate and adverse chromosomal aberrations were found in 59%, 16%, 5%, 14% and 6%, respectively. Mutated NPM1, FLT3-ITD and CEBPA genes in CN-AML were seen in 33%, 18% and 19%, respectively. A 5 year follow up, 5y-RFS was 16% and 5y-OS was 14% in the whole study population. 5y-RFS and 5y-OS in patients completed 4 cycles of consolidation therapy were 25% and 40%, respectively. Adverse cytogenetic risk and mutated FLT3-ITD were significantly associated with poor RFS (9 and 15 months, respectively) and OS (14 and 16 months, respectively), whereas patients with mutant NPM1 had favorable outcomes (RFS/OS = 51/63 months). Patients receiving 4 cycles of consolidation therapy had significantly impacts on median RFS and OS compared with those treated with 1 or 2 cycles; 15 versus 11 months (p = 0.006) and 31 versus 15 months (p < 0.001), respectively.ConclusionsCytogenetic and mutation tests for FLT3-ITD, NPM1 and CEBPA genes were meaningful for predicting outcomes in adult AML patients. Adverse cytogenetic abnormalities and FLT3-ITD mutation showed dismal RFS and OS.

Highlights

  • Cytogenetic abnormalities and mutated genes indicate the role of consolidation therapy with hematopoietic stem cell transplantation (HSCT) or chemotherapy in acute myeloid leukemia (AML)

  • There were some differences between mutation patterns of AML among Asian and Western populations; the mutations of NPM1, FMS related tyrosine kinase 3 (FLT3)-internal tandem duplications (ITDs), FLT3-tyrosine kinase domain (TKD) and CCAAT/enhancer binding protein α gene (CEBPA) were found in 16% (Asian) versus 30% (Western), 11% (Asian) versus 23% (Western), 9% (Asian) versus 10% (Western) and 21% (Asian) versus 9% (Western), respectively [6]

  • All patients were older than 15 years old and had the results of cytogenetic, FLT3-ITD, NPM1 and CEBPA gene mutation analysis

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Summary

Introduction

Cytogenetic abnormalities and mutated genes indicate the role of consolidation therapy with hematopoietic stem cell transplantation (HSCT) or chemotherapy in acute myeloid leukemia (AML). AML patients with t(8;21)(q22;q22.1), inv(16)(p13.1q22), t(16;16) (p13.1;q22), mutated NPM1 with wild type FLT3-ITD or low FLT3-ITD allele burden or biallelic CEBPA gene mutation are recommended to receive consolidation therapy with 2–4 cycles of intermediate dose Ara-C (IDAC), whereas allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is preferred for consolidation treatment in AML without favorable cytogenetics, AML with adverse risk gene mutations or AML with wild-type NPM1 and CEBPA genes [2]. We performed a retrospective study to analyze long term relapse free survival (RFS) and overall survival (OS) in adult non-transplant patients with de novo AML receiving IDAC or high dose Ara-C (HiDAC) based on clinical data, cytogenetic patterns and mutations of NPM1, FLT3-ITD and CEBPA

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