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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

RFS analysis of the alloSCT patients versus the chemotherapy-alone patients according to the NPM1mut status. (A) Overall RFS in the NPM1wt group. The overall RFS was significantly longer among the alloSCT patients than among the chemotherapy-alone patients (P=0.01). (B) Overall RFS in the NPM1mut group. A trend of longer survival was observed among the alloSCT patients than among the chemotherapy-alone patients, but the difference was not statistically significant (P=0.34). Abbreviations: NPM1mut, nucleophosmin gene mutation; NPM1wt, wild-type nucleophosmin gene; RFS, relapse-free survival; alloSCT, allogeneic stem cell transplantation.
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Figure 2: RFS analysis of the alloSCT patients versus the chemotherapy-alone patients according to the NPM1mut status. (A) Overall RFS in the NPM1wt group. The overall RFS was significantly longer among the alloSCT patients than among the chemotherapy-alone patients (P=0.01). (B) Overall RFS in the NPM1mut group. A trend of longer survival was observed among the alloSCT patients than among the chemotherapy-alone patients, but the difference was not statistically significant (P=0.34). Abbreviations: NPM1mut, nucleophosmin gene mutation; NPM1wt, wild-type nucleophosmin gene; RFS, relapse-free survival; alloSCT, allogeneic stem cell transplantation.

Mentions: In the subgroup analysis, the overall RFS was significantly longer among the patients who underwent alloSCT than among the nontransplant patients (P=0.01) in the NPM1wt group (Fig. 2A). On the other hand, in the NPM1mut group, a trend for longer RFS was observed among the alloSCT patients than the nontransplant patients, but the difference was not statistically significant (P=0.34; Fig. 2B). Although few patients underwent autoSCT (N=5), this procedure did not influence the overall relapse rate, RFS, and OS (data not shown).


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)

RFS analysis of the alloSCT patients versus the chemotherapy-alone patients according to the NPM1mut status. (A) Overall RFS in the NPM1wt group. The overall RFS was significantly longer among the alloSCT patients than among the chemotherapy-alone patients (P=0.01). (B) Overall RFS in the NPM1mut group. A trend of longer survival was observed among the alloSCT patients than among the chemotherapy-alone patients, but the difference was not statistically significant (P=0.34). Abbreviations: NPM1mut, nucleophosmin gene mutation; NPM1wt, wild-type nucleophosmin gene; RFS, relapse-free survival; alloSCT, allogeneic stem cell transplantation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: RFS analysis of the alloSCT patients versus the chemotherapy-alone patients according to the NPM1mut status. (A) Overall RFS in the NPM1wt group. The overall RFS was significantly longer among the alloSCT patients than among the chemotherapy-alone patients (P=0.01). (B) Overall RFS in the NPM1mut group. A trend of longer survival was observed among the alloSCT patients than among the chemotherapy-alone patients, but the difference was not statistically significant (P=0.34). Abbreviations: NPM1mut, nucleophosmin gene mutation; NPM1wt, wild-type nucleophosmin gene; RFS, relapse-free survival; alloSCT, allogeneic stem cell transplantation.
Mentions: In the subgroup analysis, the overall RFS was significantly longer among the patients who underwent alloSCT than among the nontransplant patients (P=0.01) in the NPM1wt group (Fig. 2A). On the other hand, in the NPM1mut group, a trend for longer RFS was observed among the alloSCT patients than the nontransplant patients, but the difference was not statistically significant (P=0.34; Fig. 2B). Although few patients underwent autoSCT (N=5), this procedure did not influence the overall relapse rate, RFS, and OS (data not shown).

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