Dataset Information

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol.

ABSTRACT: IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19−86). Of these, 38 (14%) harbored IDH1 and 51 (18%) IDH2 mutations. IDH1/2 mutations were significantly associated with WHO PS >2 (p < 0.001) and non-complex karyotype (p = 0.021) when compared to IDH1/2-WT. Furthermore, patients with IDH1 mutations were more frequently NPM1-mutated (p = 0.007) and had a higher platelet count (p = 0.036). At relapse, IDH1/2 mutations were detected in 6 (25%) patients. As per the outcome, 60.5% of IDH1/2-mutated patients achieved complete remission; overall survival and event-free survival at 2 years were 44.5% and 36.1%, respectively: these rates were similar to IDH1/2-WT. In IDH1/2-mutated patients, high WBC proved to be an independent prognostic factor for survival. In conclusion, the GIMEMA AML1516 confirms that IDH1/2 mutations are frequently detected at diagnosis and underlines the importance of recognizing IDH1/2-mutated cases up-front to offer the most appropriate therapeutic strategy, given the availability of IDH1/2 inhibitors.

SUBMITTER: Messina M

PROVIDER: S-EPMC9221405 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol.

Messina Monica M Piciocchi Alfonso A Ottone Tiziana T Paolini Stefania S Papayannidis Cristina C Lessi Federica F Fracchiolla Nicola Stefano NS Forghieri Fabio F Candoni Anna A Mengarelli Andrea A Martelli Maria Paola MP Venditti Adriano A Carella Angelo Michele AM Albano Francesco F Mancini Valentina V Massimo Bernardi B Arena Valentina V Sargentini Valeria V Sciumè Mariarita M Pastore Domenico D Todisco Elisabetta E Roti Giovanni G Siragusa Sergio S Ladetto Marco M Pravato Stefano S De Bellis Eleonora E Simonetti Giorgia G Marconi Giovanni G Cerchione Claudio C Fazi Paola P Vignetti Marco M Amadori Sergio S Martinelli Giovanni G Voso Maria Teresa MT

Cancers 20220618 12

IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19−86). Of these, 38 (14%) harbored IDH1 and 51 (18%) IDH2 mutations. IDH1/2 mutations ...[more]

PMID: 35740677

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Project description:BackgroundInterleukin-7 receptor (IL7R) mutation has been demonstrated to be an adverse prognostic factor in acute lymphoblastic leukemia (ALL) patients. However, the effects of the IL7R mutation on acute myeloid leukemia (AML) have rarely been reported. Here, we investigated IL7R mutations and their effects on AML patients.MethodsA total of 346 newly diagnosed AML patients from January 2017 to July 2020 at Nanfang Hospital were analyzed in this study. A genomic panel of 167 gene targets was detected by next-generation sequencing.ResultsAmong 346 patients, 33 (9.5%) AML patients carried IL7R mutations. With a median follow-up of 50.7 months (95% confidence interval (CI) 17.3-62.2), the 5-year overall survival (OS) rates were 51.5% (95% CI 37.0%-71.0%) and 72.2% (95% CI 67.4%-77.3%; p = 0.008), the 5-year event-free survival (EFS) rates were 36.1% (95% CI 23.2%-57.1%) and 58.1% (95% CI 52.9%-63.8%; p = 0.005), the 5-year non-relapse mortality (NRM) were 21.4% (95% CI 8.5%-38.2%) and 6.2% (95% CI 3.7%-9.5%; p = 0.004) in the IL7R mutant (IL7R MUT ) group and non-IL7R mutant (IL7R WT ) group, respectively. There is no significant difference in the disease-free survival (75.1% vs 73.5%, p = 0.885) and cumulative incidence of relapse (25.7% vs 25.2%, p = 0.933) between IL7R MUT and IL7R WT group. Furthermore, patients who underwent hematopoietic stem cell transplantation (HSCT) still had more adverse outcomes in the IL7R MUT group than in the IL7R WT group (5-year OS: 61.9% vs 85.3%, p = 0.003). In the TET2 (p = 0.013) and DNA methyltransferase 3A (DNMT3A; p = 0.046) mutation subgroups, the presence of IL7R mutations was associated with worse OS than in AML patients without IL7R mutations.ConclusionOur study demonstrated that the IL7R mutation is associated with an inferior prognosis for AML patients. Patients with IL7R mutations have higher NRM, shorter OS, and EFS than patients without IL7R mutations, even patients who have undergone HSCT. Future larger and multicentric prospective studies will be explored.

Dataset Information

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol.

Publications

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol.

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