Cytogenetics and FLT3-ITD mutation predict clinical outcomes in non transplant patients with acute myeloid leukemia

• Main Authors: Pimjai Niparuck, Nittaya Limsuwanachot, Sulada Pukiat, Pichika Chantrathammachart, Budsaba Rerkamnuaychoke, Sutada Magmuang, Sithakom Phusanti, Kochawan Boonyawat, Teeraya Puavilai, Pantep Angchaisuksiri, Artit Ungkanont, Suporn Chuncharunee
• Other Authors: Faculty of Medicine, Ramathibodi Hospital, Mahidol University
• Format: Article
• Published: 2020
• Subjects: Biochemistry, Genetics and Molecular Biology; Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/50281
• Institution: Mahidol University

© 2019 The Author(s). Background: 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. Methods: 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. Results: 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 (p = 0.006) and 31 versus 15 months (p < 0.001), respectively. Conclusions: 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.