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Prognostic significance of nucleophosmin mutations and FLT3 internal tandem duplication in adult patients with cytogenetically normal acute myeloid leukemia.

Kim YK, Kim HN, Lee SR, Ahn JS, Yang DH, Lee JJ, Lee IK, Shin MG, Kim HJ - Korean J Hematol (2010)

Bottom Line: The patients were divided according to their mutation status into the NPM1mut/FLT3-ITD (isolated NPM1mut), NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-, and NPM1wt/FLT3-ITD+ (isolated FLT3-ITD+) groups.Adult patients with CN-AML carrying isolated NPM1mut and isolated FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-.Although isolated NPM1mut leads to favorable clinical outcomes of CN-AML, the role of alloSCT in such patients remains to be considered.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology/Oncology, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Korea.

ABSTRACT

Background: Nucleophosmin (NPM1) gene and fms-like tyrosine kinase 3 gene-internal tandem duplication (FLT3-ITD) mutations are the most frequent mutations in patients with cytogenetically normal (CN)-AML. We analyzed the prognostic impact of these mutations and their interactions in adults with CN-AML.

Methods: NPM1 mutation (NPM1mut) and FLT3-ITD mutation (FLT3-ITD+) were analyzed by GeneScan and PCR assays of bone marrow samples obtained from 121 adult patients with CN-AML (age≤60 years at diagnosis).

Results: The incidence of FLT3-ITD+ was higher in the NPM1mut group than in the wild-type NPM1 gene (NPM1wt) group. The patients were divided according to their mutation status into the NPM1mut/FLT3-ITD (isolated NPM1mut), NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-, and NPM1wt/FLT3-ITD+ (isolated FLT3-ITD+) groups. The isolated NPM1mut group showed significantly better clinical outcomes in terms of relapse rate, 5-year relapse-free survival (RFS), and overall survival (OS) than the other groups. In contrast, the isolated FLT3-ITD+ group had a higher relapse rate and shorter RFS and OS than the other groups. The 5-year RFS rate was much higher among the patients who underwent allogeneic stem cell transplantation (alloSCT) than among those treated with high-dose cytarabine chemotherapy (HDAC) only as consolidation therapy in the isolated NPM1mut group and the NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD- group.

Conclusion: Adult patients with CN-AML carrying isolated NPM1mut and isolated FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-. Although isolated NPM1mut leads to favorable clinical outcomes of CN-AML, the role of alloSCT in such patients remains to be considered.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier analysis of CN-AML for RFS and OS according to the combined NPM1mut and FLT3-ITD+ status. (A) RFS and OS before transplantation. (B) Overall RFS and OS. Abbreviations: CN, cytogenetically normal; NPM1mut, nucleophosmin gene mutation; NPM1wt, wild-type nucleophosmin gene; FLT3-ITD, fms-like tyrosine kinase 3 gene-internal tandem duplication; RFS, relapse-free survival; OS, overall survival.
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Figure 3: Kaplan-Meier analysis of CN-AML for RFS and OS according to the combined NPM1mut and FLT3-ITD+ status. (A) RFS and OS before transplantation. (B) Overall RFS and OS. Abbreviations: CN, cytogenetically normal; NPM1mut, nucleophosmin gene mutation; NPM1wt, wild-type nucleophosmin gene; FLT3-ITD, fms-like tyrosine kinase 3 gene-internal tandem duplication; RFS, relapse-free survival; OS, overall survival.

Mentions: In agreement with the previous reports, our study showed that the FLT3-ITD+ status was significantly associated with NPM1mut in terms of the incidence and clinical outcomes; hence, we assessed the prognostic impact of the three groups according to the NPM1mut and FLT3-ITD+ status (Table 5). The highest remission rate was found in the NPM1mut/FLT3-ITD- group (80.0%); however, the differences among the groups were not statistically significant. The relapse rate before SCT was higher in the NPM1wt/FLT3-ITD+ group (41.7%) than in the NPM1mut/FLT3-ITD- group (21.4%) and the other groups (NPM1wt/FLT3-ITD- or NPM1mut/FLT3-ITD+, 24.5%). Furthermore, the overall relapse rate was significantly higher in the isolated FLT3-ITD+ group (83.3%) than in the isolated NPM1mut (28.6%) and the other groups (38.5%). The post hoc test also revealed that the NPM1wt/FLT3-ITD+ group had a significantly higher overall relapse rate than the NPM1mut/FLT3-ITD- (P=0.00) or the other groups (P=0.01). The highest 5-year RFS and OS were observed in the isolated NPM1mut group regardless of SCT, followed by the NPM1wt/FLT3-ITD- or NPM1mut/FLT3-ITD+ group and the isolated FLT3-ITD+ groups (Fig. 3).


Prognostic significance of nucleophosmin mutations and FLT3 internal tandem duplication in adult patients with cytogenetically normal acute myeloid leukemia.

Kim YK, Kim HN, Lee SR, Ahn JS, Yang DH, Lee JJ, Lee IK, Shin MG, Kim HJ - Korean J Hematol (2010)

Kaplan-Meier analysis of CN-AML for RFS and OS according to the combined NPM1mut and FLT3-ITD+ status. (A) RFS and OS before transplantation. (B) Overall RFS and OS. Abbreviations: CN, cytogenetically normal; NPM1mut, nucleophosmin gene mutation; NPM1wt, wild-type nucleophosmin gene; FLT3-ITD, fms-like tyrosine kinase 3 gene-internal tandem duplication; RFS, relapse-free survival; OS, overall survival.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2983002&req=5

Figure 3: Kaplan-Meier analysis of CN-AML for RFS and OS according to the combined NPM1mut and FLT3-ITD+ status. (A) RFS and OS before transplantation. (B) Overall RFS and OS. Abbreviations: CN, cytogenetically normal; NPM1mut, nucleophosmin gene mutation; NPM1wt, wild-type nucleophosmin gene; FLT3-ITD, fms-like tyrosine kinase 3 gene-internal tandem duplication; RFS, relapse-free survival; OS, overall survival.
Mentions: In agreement with the previous reports, our study showed that the FLT3-ITD+ status was significantly associated with NPM1mut in terms of the incidence and clinical outcomes; hence, we assessed the prognostic impact of the three groups according to the NPM1mut and FLT3-ITD+ status (Table 5). The highest remission rate was found in the NPM1mut/FLT3-ITD- group (80.0%); however, the differences among the groups were not statistically significant. The relapse rate before SCT was higher in the NPM1wt/FLT3-ITD+ group (41.7%) than in the NPM1mut/FLT3-ITD- group (21.4%) and the other groups (NPM1wt/FLT3-ITD- or NPM1mut/FLT3-ITD+, 24.5%). Furthermore, the overall relapse rate was significantly higher in the isolated FLT3-ITD+ group (83.3%) than in the isolated NPM1mut (28.6%) and the other groups (38.5%). The post hoc test also revealed that the NPM1wt/FLT3-ITD+ group had a significantly higher overall relapse rate than the NPM1mut/FLT3-ITD- (P=0.00) or the other groups (P=0.01). The highest 5-year RFS and OS were observed in the isolated NPM1mut group regardless of SCT, followed by the NPM1wt/FLT3-ITD- or NPM1mut/FLT3-ITD+ group and the isolated FLT3-ITD+ groups (Fig. 3).

Bottom Line: The patients were divided according to their mutation status into the NPM1mut/FLT3-ITD (isolated NPM1mut), NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-, and NPM1wt/FLT3-ITD+ (isolated FLT3-ITD+) groups.Adult patients with CN-AML carrying isolated NPM1mut and isolated FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-.Although isolated NPM1mut leads to favorable clinical outcomes of CN-AML, the role of alloSCT in such patients remains to be considered.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology/Oncology, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Korea.

ABSTRACT

Background: Nucleophosmin (NPM1) gene and fms-like tyrosine kinase 3 gene-internal tandem duplication (FLT3-ITD) mutations are the most frequent mutations in patients with cytogenetically normal (CN)-AML. We analyzed the prognostic impact of these mutations and their interactions in adults with CN-AML.

Methods: NPM1 mutation (NPM1mut) and FLT3-ITD mutation (FLT3-ITD+) were analyzed by GeneScan and PCR assays of bone marrow samples obtained from 121 adult patients with CN-AML (age≤60 years at diagnosis).

Results: The incidence of FLT3-ITD+ was higher in the NPM1mut group than in the wild-type NPM1 gene (NPM1wt) group. The patients were divided according to their mutation status into the NPM1mut/FLT3-ITD (isolated NPM1mut), NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-, and NPM1wt/FLT3-ITD+ (isolated FLT3-ITD+) groups. The isolated NPM1mut group showed significantly better clinical outcomes in terms of relapse rate, 5-year relapse-free survival (RFS), and overall survival (OS) than the other groups. In contrast, the isolated FLT3-ITD+ group had a higher relapse rate and shorter RFS and OS than the other groups. The 5-year RFS rate was much higher among the patients who underwent allogeneic stem cell transplantation (alloSCT) than among those treated with high-dose cytarabine chemotherapy (HDAC) only as consolidation therapy in the isolated NPM1mut group and the NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD- group.

Conclusion: Adult patients with CN-AML carrying isolated NPM1mut and isolated FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-. Although isolated NPM1mut leads to favorable clinical outcomes of CN-AML, the role of alloSCT in such patients remains to be considered.

No MeSH data available.


Related in: MedlinePlus