Niparuck Pimjai, Limsuwanachot Nittaya, Pukiat Sulada, Chantrathammachart Pichika, Rerkamnuaychoke Budsaba, Magmuang Sutada, Phusanti Sithakom, Boonyawat Kochawan, Puavilai Teeraya, Angchaisuksiri Pantep, Ungkanont Artit, Chuncharunee Suporn
Division of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Human Genetics Laboratory, Department of Pathology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Exp Hematol Oncol. 2019 Jan 30;8:3. doi: 10.1186/s40164-019-0127-z. eCollection 2019.
Cytogenetic 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.
We 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.
Normal 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 ( = 0.006) and 31 versus 15 months ( < 0.001), respectively.
Cytogenetic 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.
细胞遗传学异常和基因突变表明了造血干细胞移植（HSCT）或化疗巩固治疗在急性髓系白血病（AML）中的作用。在本研究中，我们对新诊断为原发性AML且未接受HSCT的成年AML患者进行了一项回顾性研究，以探讨巩固化疗后的长期无复发生存期（RFS）和总生存期（OS）。
我们招募了2010年1月至2017年6月期间连续的141例AML患者，这些患者接受了标准剂量阿糖胞苷和伊达比星的诱导化疗（7 + 3或5 + 2方案），随后进行中剂量（IDAC）或大剂量阿糖胞苷（HiDAC）巩固治疗。
正常核型、复杂、有利、中等和不良染色体畸变分别在59%、16%、5%、14%和6%的患者中发现。在CN-AML中，NPM1、FLT3-ITD和CEBPA基因的突变分别见于33%、18%和19%的患者。经过5年随访，整个研究人群的5年RFS为16%，5年OS为14%。完成4个周期巩固治疗的患者的5年RFS和5年OS分别为25%和40%。不良细胞遗传学风险和FLT3-ITD突变与较差的RFS（分别为9个月和15个月）和OS（分别为14个月和16个月）显著相关，而NPM1突变的患者预后良好（RFS/OS = 51/63个月）。与接受1或2个周期治疗的患者相比，接受4个周期巩固治疗的患者对中位RFS和OS有显著影响；分别为15个月对11个月（P = 0.006）和31个月对15个月（P < 0.001）。
对FLT3-ITD、NPM1和CEBPA基因进行细胞遗传学和突变检测对预测成年AML患者的预后有意义。不良细胞遗传学异常和FLT3-ITD突变显示出较差的RFS和OS。
