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Mutations of the genes associating with cell differentiation or proliferation are recognized as factors of tumorigenesis or prognosis in hematological malignancies. In pediatric acute lymphoblastic ...leukemia (ALL), alterations of IKZF1 (a factor of lymphocyte differentiation), TP53 (a cell cycle regulator) and CREBBP (a histone modifier) are found as possible prognostic markers for stratification of treatments. On the other hand, in adult ALL, clinical significance of such alterations remains to be determined. In the present work, we examined whether the mutations in those genes affected the incidence and prognosis in adult ALL patients.
We investigated 87 adult patients with newly diagnosed ALL treated with JALSG protocols between 1986 and 2011. Age ranged from 15 to 86 years, with a median of 51 years. We obtained cDNA and genomic DNA from the peripheral blood or bone marrow mononuclear cells at diagnosis. CREBBP mutations are dominantly identified in the histone acetyltransferase (HAT) domain. HAT domain in the CREBBP gene was amplified by PCR using cDNA and was subjected to direct sequencing. Additionally other histone modifiers, EZH2, EED, and UTX, were sequenced as the same as in CREBBP. TP53 exons 5 – 8 and 10, in which mutations were commonly reported, were sequenced using genomic DNA. We amplified IKZF1 using RT-PCR for detecting aberrant dominant negative isoforms: Ik6 and Ik10. Genomic deletions of IKZF1 were assessed with RQ-PCR or genomic DNA PCR. We compared clinical profiles between patients with and without such gene mutations. The present study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the revised Declaration of Helsinki.
In 87 adult patients with ALL, alterations of CREBBP, EED, TP53 and IKZF1 were detected in 7 (9.5%), 3 (4.8%), 6 (6.9%) and 42 (50%), respectively. None of EZH2 and UTX mutation was found. The alterations of CREBBP and IKZF1 at diagnosis in adult patients were more frequent than those in pediatric patients ever reported. Some gene mutations were not found frequently. Each gene mutation per se did not significantly affect prognosis. We tried to predict the prognosis by scoring gene mutations and chromosomal abnormalities. Philadelphia chromosome (Ph) has great impact to prognosis of patients with ALL. We scored the number of mutated genes and Ph for each patient. As the score was higher, adult patients with ALL had poorer relapse-free survival (P=0.0439) and OS (P=0.4819), but statistical significance was not detected in this small cohort.
Single gene mutations, such as IKZF1, can predict the prognosis in pediatric ALL. In adult ALL, however, only few gene mutations are reported to be promising prognostic factors which have impacts to treatment outcomes. Scoring system may be a useful method for predicting prognosis and stratifying treatment in adult ALL. Our study implies the possibility that a variety and heterogeneity of genetic alterations in adult ALL are associated with the pathogenesis for treatment resistance and prognostic marker of adult ALL.
No relevant conflicts of interest to declare.
Background:
Adult T-cell leukemia-lymphoma (ATL), which is a hematological malignancy related to human T-lymphotropic virus type I (HTLV-1), is known as a malignant lymphoid disease with poor ...prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered a treatment modality to contribute prolonging the survival in some population of patients (Katsuya H et al. 2015 Blood). A small study indicated that ATL cells frequently have chromosomal abnormalities including various numerical aberrations and complex structural abnormalities (Kamada N et al. Cancer Res. 1992). However, there has been no large study to examine the relationship between chromosomal abnormalities and survival. Here we report the impact of chromosomal abnormalities on survival in ATL patients with conventional chemotherapy.
Patients and Methods:
In this study, we extracted a population of patients from the database of ATL-PI project, which is a nation-wide survey of ATL patients newly diagnosed between January 2000 and May 2009, and the overall results were reported elsewhere (Katsuya H et al. JCO 2012, Blood 2015). Fifteen hundred and twelve patients were registered in this project, and we excluded the patients who received allo-HSCT, and who were diagnosed with smoldering and chronic type ATL. Moreover, patients whose chromosomal analysis with G-banding stain showed normal, multiploid or no mitosis, or no information on chromosomal analysis and on the factors to determine the ATL-PI were also excluded. As a consequence, 210 patients with acute (n=157) and lymphoma (n=53) types were selected for this analysis. Abnormal karyotypes were analyzed from the aspect of numerical and structural break points. To identify the specific abnormalities and to avoid the secondary changes, the stem-line karyotype, which meant the simplest abnormal clone, was used as the representative karyotype for this study. A statistical analysis was performed with 'EZR' (Kanda T. BMT 2013). We examined an overall survival (OS) in relation to chromosomal abnormalities using cox proportional hazard regression model, and p-value of less than 0.05 was considered as statistically significant.
Results:
Among the 210 patients, 119 and 91 patients were male and female, respectively. The median age of patients was 66 years (40-89). With respect to other factors of ATL-PI, the median level of soluble interleukin-2 receptor (sIL-2R), serum albumin, were 30800 U/mL (620-1,219,000), 3.6 g/dL (1.6-5.3), respectively. Almost all patients were diagnosed with stage II-IV of clinical stage (n=200), and almost half of patients certified 2-4 of ECOG-PS (n=113). Sixty-nine, 106, and 35 patients were classified as high, intermediate and low risk by ATL-PI, respectively. Specimens used for chromosomal analysis were taken from lymph nodes (n=77), bone marrow (n=72), peripheral blood (n=50), pleural fluids (n=4), ascites (n=4) and 1 each of stomach, sinusoidal tumor, and tonsillar lesions. The median number of numerical abnormalities and marker chromosomes were 2 (0-20) and 1 (0-20), and the median number of structural break points was 6 (0-21). The numerical abnormalities were loss of sex chromosomes (31%) followed in decreasing order by -14 (24%), -13 (19%), -9 (12%) and -17 (12%) while the structural break points were located at 1p (30%), 3q (30%), 14q (30%), 6q (26%) and 1q (22%). The median OS was 286 days (1-2565). ECOG-PS, serum albumin level, sIL-2R, and structural break points at 9q or 19p, and the number of structural break points over 4 or 5 points were shown to be the significant factors affecting the survival by univariate analysis. Then, the multivariate analysis indicated that 2-4 of ECOG-PS (HR: 2.021, 95%CI: 1.436-2.791, p<0.001), serum albumin level < 3.5 g/dl (HR: 1.631, 95%CI: 1.282-2.074, P<0.001), and chromosomally structural break points at 9q (HR: 1.584, 95%CI: 1.096-2.289, p<0.001) and 19p (HR: 1.765, 95%CI: 1.038-2.999, p<0.001) were factors that negatively contributed to OS.
Discussions and Conclusion:
This is the first large study showing the impact of chromosomal abnormality in acute and lymphoma types ATL on OS. It demonstrated that structural break points at 9q and 19p were the independent risk factors for OS in addition to those of ATL-PI.
Katsuya:The Uehara Memorial Foundation: Research Funding. Utsunomiya:Daiichi Sankyo Co., Ltd.: Speakers Bureau. Tsukasaki:Daiichi Sankyo Co., Ltd.: Consultancy; Takeda: Research Funding. Suzumiya:Takeda: Honoraria; Astellas: Research Funding; Kyowa Hakko kirin: Research Funding; Chugai: Honoraria, Research Funding; Toyama Chemical: Research Funding; Eisai: Honoraria, Research Funding.
Abstract 2538
Among acute myeloid leukemia (AML) patients with intermediate-risk cytogenetics, C/EBPa mutations represent a distinct disease entity with a favorable clinical outcome and is adopted in ...the current WHO classification of AML as a provisional disease entity in the category AML with recurrent genetic abnormalities. CEBPA encodes a transcription factor that is essential for neutrophil development. AML patients with CEBPA mutations can be separated into two subgroups with a single mutation in the CEBPA (CEBPA sm) and double mutations (CEBPA dm). Biallelic mutations consisted of an N-terminal frameshift mutation and a C-terminal inframe bZIP mutation were detected in the majority of CEBPA dm, whereas CEBPA sm occurs in either N-terminal or C-terminal regions. More recent data indicate that favorable outcome is mainly observed in AML patients with CEBPA dm but not with CEBPA sm. In addition, concurrent gene mutations may occur more frequently in AML with CEBPA sm than in CEBPA dm. In contrast, transcription factor GATA2 mutations are frequently identified in AML with CEBPA dm. In this study, we examined incidence, concurrent gene mutations and clinical significance of CEBPA dm and CEBPA sm in Japanese adults with cytogenetically intermediate-risk AML.
To identify the prevalence and prognostic impact of CEBPA dm and CEBPA sm, we examined 111 patients with intermediate-risk AML who were mainly treated with the JALSG protocols. Age ranged from 16 to 86 years, with a median of 58.5 years. DNA was extracted from bone marrow or peripheral blood mononuclear cells at diagnosis and subjected to PCR amplification and direct sequencing of the CEBPA, FLT3, NPM1, IDH1, IDH2, DNMT3A and GATA2 genes. This study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the revised Declaration of Helsinki.
Of 111 cytogenetically intermediate-risk AML, we found 12 (10.8%) CEBPA dm and 7 (6.3%) CEBPA sm. In 7 CEBPA sm, one NPM1 mutation and one FLT3-ITD were detected. Two FLT 3-ITD and no concurrent mutation of NPM1 were found in CEBPA dm. No mutation in the IDH1, IDH2, DNMT3A exon 23 was identified in both patients with CEBPA sm and CEBPA dm. On the other hand, mutations in the GATA2 zinc finger domains were detected in 3 of 12 (25%) patients with CEBPA dm. No GATA2 mutations were found in 7 CEBPA sm. One of 21 patients with wild-type CEBPA (CEBPA wt) had a GATA2 mutation. Patients with CEBPA double or single mutations showed a better 5-year overall survival (OS) compared to CEBPA wt (51.3% vs 16.0%, P=0.0048). CEBPA dm AML was associated with a significant superior clinical outcome compared with CEBPA wt (5-year OS, 55.6% vs 16.0%, P=0.0025). However, no significant difference was identified between CEBPA dm and CEBPA sm AML (5-years OS, 55.6% vs 42.9%, P=0.1375) or between CEBPA sm and CEBPA wt AML (5-year OS, 42.9% vs 16.0%, P=0.4827). In addition, the presence of additional GATA2 mutations did not significantly influence the clinical outcome of AML patients with CEBPA dm.
A total of 19 (17.1%) patients with cytogenetically intermediate-risk AML harbored CEBPA mutations. Our study indicates that the presence of the CEBPA dm but not CEBPA sm is associated with favorable outcome in Japanese patients with cytogenetically intermediate-risk AML.
No relevant conflicts of interest to declare.
Abstract 1419
Molecular pathogenesis of acute lymphoblastic leukemia (ALL) has largely been verified in pediatric patients and the identification of genetic alterations have contributed to ...stratifying therapeutic applications. In adult patients with ALL, cytogenetic and genetic abnormalities have not sufficiently been elucidated and therapeutic improvement has been hindered. CREB binding protein (CREBBP) is a transcriptional coactivator that interacts with a diverse range of transcription factors and regulates transcription by histone acetylation in hematopoiesis. Mutations of the CREBBP gene are recently found in approximately 2–4% of pediatric patients with ALL. Especially in relapsed cases, the mutations prevail (18–63%) and are possible markers for prediction of relapse in pediatric ALL. In adult patients with ALL, the clinical significance of CREBBP mutations remains to be determined. Here we examined adult ALL patients in an attempt to determine the incidence, clinical characteristics and prognostic impact of the CREBBP mutations.
We investigated 71 adult patients with newly diagnosed ALL treated with JALSG protocols between 1986 and 2010. Age ranged from 15 to 86 years, with a median of 54 years. CREBBP mutations are dominantly identified in histone acetyltransferase (HAT) domain. HAT domain in the CREBBP gene was amplified with RT-PCR using RNA isolated from the peripheral blood or bone marrow mononuclear cells at diagnosis and was subjected to direct sequencing. We compared clinical profiles between patients with and without CREBBPHAT domain mutations. This study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the revised Declaration of Helsinki.
CREBBP HAT domain mutations were detected in 8 of 71 (11.3%) patients: one nonsense mutation, five insertion mutations with frameshifts, and five missense mutations. Two patients harbored biallelic mutations. The mutations at diagnosis in adult patients were seen more frequently than those in pediatric patients ever reported. Such mutations were not completely identical to those detected in pediatric ALL, but were seen in the region within the HAT domain, indicating that such mutations are loss-of-function mutations. The mutations were found in both B-cell (6/53: 11.3%) and T-cell (1/9: 11.1%) ALL, and distributed in patients harboring IKZF1 alterations (3/31: 9.7%) or the BCR-ABL fusion gene (2/19: 10.5%). There were no statistical difference in age, sex, leukocyte, platelet counts and complete remission rate between patients with and without the CREBBP HAT domain mutations. Patients with the mutations had a trend with worse cumulative incidence of relapse (P=0.4637), relapse-free survival (P=0.4195) and OS (P=0.2349) compared to patients lacking the mutations, but statistical significance was not detected in this small cohort.
CREBBP HAT domain mutations at diagnosis in adult ALL are found more frequently than in pediatric ALL. This may be one of the mechanisms that adult ALL has been associated with poor OS compared with pediatric ALL. In this study, CREBBP HAT domain mutations were observed in various subtypes of ALL: both B-cell and T-cell ALL, and both Philadelphia chromosome positive and negative ALL. In pediatric ALL, CREBBP mutations were frequently seen in relapsed patients but not in previously untreated patients. These observations suggest that CREBBP mutations play an important role in an additional late event(s) leading to the development and progression of ALL. Our study implies the possibility that mutations of the CREBBP gene are associated with the pathogenesis and prognostic marker of adult ALL and represent specific epigenetic modifiers in adult ALL, serving as potential therapeutic targets.
No relevant conflicts of interest to declare.
Abstract
Purpose
Recurrent mutations in the genes coding the isocitrate dehydrogenases IDH1 and IDH2 have recently been identified in patients with acute myeloid leukemia (AML). However, the ...prognostic importance of IDH1 and IDH2 mutations is not consistent among several studies. In the present study, we examined the incidence and prognostic impacts of IDH1 and IDH2 mutations in Japanese adults with AML.
Patients and Methods
A total of 233 adults with AML were subjected to the study. Age ranged from 15 to 86 years, with a median of 57.0 years. Patients with aged 69 or less were treated with the protocols of Japan Adult Leukemia Study Group (JALSG). Patients with aged 70 or more were treated with low dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) (Suzushima et al. Leuk Res 2010). DNA was extracted from bone marrow or peripheral blood mononuclear cells of AML patients at diagnosis and subjected to PCR amplification and direct sequencing of the IDH1 and IDH2 genes. NPM1, FLT3 and CEBPA gene mutations were also analyzed. The study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the tenets of the revised Declaration of Helsinki.
Results
IDH1 R132 mutations were detected in 20 (8.6%) patients with AML. IDH2 mutations were found in 19 (8.2%; 17 R140 and two R172) patients. IDH1 and IDH2 mutations were mutually exclusive and were most frequent in the cytogenetic intermediate-risk group. In addition, IDH1 and IDH2 mutations were mutually exclusive with the CEBPA mutation. Moreover, IDH1 and IDH2 mutations were associated with NPM1 mutations. Of 39 patients with IDH mutations, 17 (44%) had the NPM1 mutation, whereas 36 of 194 (19%) lacking an IDH mutation had an NPM1 mutation (P = 0.001). There was no significant correlation of the IDH mutation with FLT3-ITD. Of 226 patients evaluable for treatment outcome, there was no significant difference in 5-year overall survival (OS) between patients with and those without IDH1 mutations (25.1% vs. 29.9%, P = 0.3089). In contrast, 5-year OS rates were significantly lower (6.2%) in patients harboring the IDH2 mutation than in patients lacking the IDH2 mutation (31.5%) in the entire cohort of AML (P = 0.0026). Because IDH1 and IDH2 mutations were associated with NPM1 mutations, we compared OS in patients with and those without IDH1 or IDH2 mutations among patients with and those without NPM1 mutations. Of 51 patients with NPM1 mutations, there was no significant difference in 5-year OS between patients with and those without the IDH1 or IDH2 mutation. In contrast, among 175 patients lacking the NPM1 mutation, 5-year OS in patients with IDH1 or IDH2 mutations was significantly lower than in those without such mutations (0% vs. 32.4%, P = 0.0023 and 0% vs. 32.6%, P = 0.0001, respectively). Moreover, among patients with the wild-type of NPM1, 5-year OS in patients with IDH1 or IDH2 mutations was significantly lower than that in those with the CEBPA mutation, FLT3-ITD, or the wild-type of CEBPA, FLT3, IDH1 and IDH2 (P=0.0002).
Conclusions
Frequent mutations in IDH1 and IDH2 are also found in Japanese adults with AML. Our data strongly suggest that IDH1 and IDH2 mutations confer adverse prognostic effect in NPM1 wild-type AML. On the other hand, an adverse effect of IDH1 and IDH2 mutations may be negated among patients with NPM1 mutations, because NPM1 mutations generally have a higher complete remission rate and more favorable OS.
Disclosures:
No relevant conflicts of interest to declare.
Recurrent mutations in the genes coding the isocitrate dehydrogenases IDH1 and IDH2 have recently been identified in patients with acute myeloid leukemia (AML). However, the prognostic importance of ...IDH1 and IDH2 mutations is not consistent among several studies. In the present study, we examined the incidence and prognostic impacts of IDH1 and IDH2 mutations in Japanese adults with AML.
A total of 233 adults with AML were subjected to the study. Age ranged from 15 to 86 years, with a median of 57.0 years. Patients with aged 69 or less were treated with the protocols of Japan Adult Leukemia Study Group (JALSG). Patients with aged 70 or more were treated with low dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) (Suzushima et al. Leuk Res 2010). DNA was extracted from bone marrow or peripheral blood mononuclear cells of AML patients at diagnosis and subjected to PCR amplification and direct sequencing of the IDH1 and IDH2 genes. NPM1, FLT3 and CEBPA gene mutations were also analyzed. The study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the tenets of the revised Declaration of Helsinki.
IDH1 R132 mutations were detected in 20 (8.6%) patients with AML. IDH2 mutations were found in 19 (8.2%; 17 R140 and two R172) patients. IDH1 and IDH2 mutations were mutually exclusive and were most frequent in the cytogenetic intermediate-risk group. In addition, IDH1 and IDH2 mutations were mutually exclusive with the CEBPA mutation. Moreover, IDH1 and IDH2 mutations were associated with NPM1 mutations. Of 39 patients with IDH mutations, 17 (44%) had the NPM1 mutation, whereas 36 of 194 (19%) lacking an IDH mutation had an NPM1 mutation (P = 0.001). There was no significant correlation of the IDH mutation with FLT3-ITD. Of 226 patients evaluable for treatment outcome, there was no significant difference in 5-year overall survival (OS) between patients with and those without IDH1 mutations (25.1% vs. 29.9%, P = 0.3089). In contrast, 5-year OS rates were significantly lower (6.2%) in patients harboring the IDH2 mutation than in patients lacking the IDH2 mutation (31.5%) in the entire cohort of AML (P = 0.0026). Because IDH1 and IDH2 mutations were associated with NPM1 mutations, we compared OS in patients with and those without IDH1 or IDH2 mutations among patients with and those without NPM1 mutations. Of 51 patients with NPM1 mutations, there was no significant difference in 5-year OS between patients with and those without the IDH1 or IDH2 mutation. In contrast, among 175 patients lacking the NPM1 mutation, 5-year OS in patients with IDH1 or IDH2 mutations was significantly lower than in those without such mutations (0% vs. 32.4%, P = 0.0023 and 0% vs. 32.6%, P = 0.0001, respectively). Moreover, among patients with the wild-type of NPM1, 5-year OS in patients with IDH1 or IDH2 mutations was significantly lower than that in those with the CEBPA mutation, FLT3-ITD, or the wild-type of CEBPA, FLT3, IDH1 and IDH2 (P=0.0002).
Frequent mutations in IDH1 and IDH2 are also found in Japanese adults with AML. Our data strongly suggest that IDH1 and IDH2 mutations confer adverse prognostic effect in NPM1 wild-type AML. On the other hand, an adverse effect of IDH1 and IDH2 mutations may be negated among patients with NPM1 mutations, because NPM1 mutations generally have a higher complete remission rate and more favorable OS.
No relevant conflicts of interest to declare.
Abstract
We examined the incidence and prognostic effect of
IDH
1
and
IDH
2
mutations in 233 Japanese adults with acute myeloid leukemia (
AML
).
IDH
1
R132 mutations were detected in 20 (8.6%) ...patients with
AML
.
IDH
2
mutations were found in 19 (8.2%, 17
R
140 and two
R
172) patients.
IDH
1
and
IDH
2
mutations were mutually exclusive and were associated with normal karyotype
AML
, cytogenetic intermediate‐risk group, and
NPM
1
mutations. Five‐year overall survival (
OS
) rates were significantly lower (15.6%) in patients harboring the
IDH
mutations than in patients lacking the
IDH
mutation (32.0%) in the entire cohort of
AML
(
P
=
0.005). Among patients aged 59 yr or younger with
IDH
mutations, 5‐yr
OS
in patients who underwent allogeneic stem cell transplantation (
SCT
) was significantly higher than that in those not receiving allogeneic
SCT
(50% vs. 10.6%,
P
=
0.020). Of 51 patients with
NPM
1
mutations, there was no significant difference in 5‐yr
OS
rates between patients with and those without the
IDH
mutations. In contrast, among 175 patients lacking the
NPM
1
mutations, 5‐yr
OS
rate in patients with
IDH
mutations was significantly lower than that in those without
IDH
mutations (0% vs. 34.7%,
P
= <0.001). These data suggest that
IDH
mutations have an unfavorable effect in
AML
, especially
AML
with the
NPM
1
wild type and younger
AML
patients with
IDH
mutations may benefit from allogeneic
SCT
.
Abstract 2519
Recurrent mutations in the genes coding the isocitrate dehydrogenases, IDH1 and IDH2, have recently been demonstrated in patients with acute myeloid leukemia (AML). However, it remains ...to be determined how frequently IDH1 and IDH2 mutations occur in Asian AML patients and whether IDH1 and IDH2 mutations are associated with clinical profiles and outcome. In this study, we examined the incidence and prognostic impacts of IDH1 and IDH2 mutations in Japanese adults with AML.
A total of 190 adults with AML were subjected to the study. Age ranged from 15 to 86 years, with a median of 57.0 years. Patients with aged 69 or less were treated with the protocols of Japan Adult Leukemia Study Group (JALSG). Patients aged 70 or more were treated with low dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) (Suzushima et al. Leuk Res 2010). DNA was extracted from bone marrow or peripheral blood mononuclear cells of AML patients at diagnosis and subjected to PCR amplification and direct sequencing of the IDH1 and IDH2 genes. NPM1, FLT3 and CEBPA gene mutations were also analyzed. The study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the tenets of the revised Declaration of Helsinki.
IDH1 R132 mutations were detected in 16 patients (8.4%). IDH2 mutations were found in 18 patients (9.5%; 17 with R140 and one with R172). IDH1 and IDH2 mutations had mutually exclusively occurred. IDH1 mutation was associated with higher platelet counts and was more frequent with M1 in FAB classification. IDH2 mutation was associated with ages, lower leukocyte counts and was more frequent with M0. Median age of patients with IDH2 mutation was 63.5 years, while that with wild type was 55.5 years (P=0.036). No IDH2 mutation was observed in patients aged 39 or less. Both IDH1 and IDH2 mutations were most frequent in cytogenetically normal AML and cytogenetic intermediate-risk group. Although IDH1 mutations were not significantly associated with mutations in NPM1 and FLT3, IDH2 mutations were associated with NPM1 mutations. Of 15 IDH2 mutations, 8 (53%) had NPM1 mutation, whereas 26 of 121 (21%) lacking IDH2 mutation had NPM1 mutation (P=0.012). Interestingly, both IDH1 and IDH2 mutations were mutually exclusive with CEBPA mutations. There was no significant difference in 5-year overall survival (OS) between patients with and without IDH1 mutation (32.6% vs. 26.7%, P=0.7377). In contrast, 5-year OS rates were 6.6% for patients harboring IDH2 mutation and 34.5% for patients lacking IDH2 mutation in the entire cohort of AML (P=0.0020). This unfavorable effect was also found in cytogenetically normal AML (P=0.0383). Of patients aged 59 or less, there was no significant difference in 5-year OS between IDH2 mutations (14.3%) and wild-type (43.3%) (P=0.1440). On the other hand, among patients aged 60 or older, 5-year OS rates were 0% for patients carrying IDH2 mutation and 21.6% for patients lacking IDH2 mutation (P=0.0100).
Frequent mutations in IDH1 and IDH2 are also found in Japanese adults with AML. Our study indicates that IDH2 mutation has an unfavorable impact on the treatment outcome in adult patients with AML, especially in older (age ≥60 years) patients. These data suggest that IDH2 mutation confer a significant adverse impact on elderly patients with AML.
No relevant conflicts of interest to declare.
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