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

Abstract 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...

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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
Format: Article
Language:English
Published: BMC 2019-01-01
Series:Experimental Hematology & Oncology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40164-019-0127-z
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author Pimjai Niparuck
Nittaya Limsuwanachot
Sulada Pukiat
Pichika Chantrathammachart
Budsaba Rerkamnuaychoke
Sutada Magmuang
Sithakom Phusanti
Kochawan Boonyawat
Teeraya Puavilai
Pantep Angchaisuksiri
Artit Ungkanont
Suporn Chuncharunee
author_facet Pimjai Niparuck
Nittaya Limsuwanachot
Sulada Pukiat
Pichika Chantrathammachart
Budsaba Rerkamnuaychoke
Sutada Magmuang
Sithakom Phusanti
Kochawan Boonyawat
Teeraya Puavilai
Pantep Angchaisuksiri
Artit Ungkanont
Suporn Chuncharunee
author_sort Pimjai Niparuck
collection DOAJ
description Abstract 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.
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spelling doaj.art-dfbdca18c00747419aff4015339559802022-12-22T01:54:42ZengBMCExperimental Hematology & Oncology2162-36192019-01-018111410.1186/s40164-019-0127-zCytogenetics and FLT3-ITD mutation predict clinical outcomes in non transplant patients with acute myeloid leukemiaPimjai Niparuck0Nittaya Limsuwanachot1Sulada Pukiat2Pichika Chantrathammachart3Budsaba Rerkamnuaychoke4Sutada Magmuang5Sithakom Phusanti6Kochawan Boonyawat7Teeraya Puavilai8Pantep Angchaisuksiri9Artit Ungkanont10Suporn Chuncharunee11Division of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol UniversityHuman Genetics Laboratory, Department of Pathology, Ramathibodi Hospital, Mahidol UniversityDivision of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol UniversityDivision of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol UniversityHuman Genetics Laboratory, Department of Pathology, Ramathibodi Hospital, Mahidol UniversityHuman Genetics Laboratory, Department of Pathology, Ramathibodi Hospital, Mahidol UniversityDivision of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol UniversityDivision of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol UniversityDivision of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol UniversityDivision of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol UniversityDivision of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol UniversityDivision of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol UniversityAbstract 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.http://link.springer.com/article/10.1186/s40164-019-0127-zAcute myeloid leukemiaCytogeneticsFLT3-ITDNPM1CEBPA
spellingShingle Pimjai Niparuck
Nittaya Limsuwanachot
Sulada Pukiat
Pichika Chantrathammachart
Budsaba Rerkamnuaychoke
Sutada Magmuang
Sithakom Phusanti
Kochawan Boonyawat
Teeraya Puavilai
Pantep Angchaisuksiri
Artit Ungkanont
Suporn Chuncharunee
Cytogenetics and FLT3-ITD mutation predict clinical outcomes in non transplant patients with acute myeloid leukemia
Experimental Hematology & Oncology
Acute myeloid leukemia
Cytogenetics
FLT3-ITD
NPM1
CEBPA
title Cytogenetics and FLT3-ITD mutation predict clinical outcomes in non transplant patients with acute myeloid leukemia
title_full Cytogenetics and FLT3-ITD mutation predict clinical outcomes in non transplant patients with acute myeloid leukemia
title_fullStr Cytogenetics and FLT3-ITD mutation predict clinical outcomes in non transplant patients with acute myeloid leukemia
title_full_unstemmed Cytogenetics and FLT3-ITD mutation predict clinical outcomes in non transplant patients with acute myeloid leukemia
title_short Cytogenetics and FLT3-ITD mutation predict clinical outcomes in non transplant patients with acute myeloid leukemia
title_sort cytogenetics and flt3 itd mutation predict clinical outcomes in non transplant patients with acute myeloid leukemia
topic Acute myeloid leukemia
Cytogenetics
FLT3-ITD
NPM1
CEBPA
url http://link.springer.com/article/10.1186/s40164-019-0127-z
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