High IL1R1 expression predicts poor survival and benefit from stem cell transplant in intermediate-risk acute myeloid leukemia from the Leucegene cohort

IL1R1 Expression Predicts the Benefit from Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Intermediate-Risk Cytogenetics

High Expression of SPAG1 Is Associated with a Worse Clinical Outcome in Intermediate Risk Acute Myeloid Leukemia That Can be Partially Overcome By Hematopoietic Stem Cell Transplantation

Identification of Novel Antigens for Normal Karyotype Triple Mutated Acute Myeloid Leukemia

Prognostic Value of Molecular Markers for Guiding Post-Remission Therapy in Patients with De Novo Acute Myeloid Leukemia (AML) and Intermediate-Risk Cytogenetics

Assessment of CEBPA Mutations Might Contribute to a Better Prognostic Assignment in Patients with Intermediate-Risk Cytogenetics Acute Myeloid Leukemia (AML).

Allogeneic Hematopoietic Stem-Cell Transplantation (HSCT) in First Complete Remission Is Superior Compared to Chemotherapy/Autologous HSCT in Patients with Intermediate-Risk Cytogenetics Acute Myeloid Leukemia Lacking Mutations in NPM1, FLT3-ITD, and CEBPA: A Joint Study of AMLSG, Cetlam and Acute Leukemia Working Party of EBMT

Objective To analyze clinical characteristics of cytogenetically normal acute myeloid leukemia (CN-AML) patients with DNMT3A, FLT3-ITD and NPM1 mutations (DNMT3A/FLT3-ITD/NPM1+), and explore the prognosis of these patients. Methods The clinical characteristics and prognosis of 109 CN-AML patients in our center from Dec 2005 to Oct 2014 were retrospectively analyzed. Based on gene mutations, these patients were divided into 4 groups: DNMT3A/FLT3-ITD/NPM1+ AML patients (n = 25), FLT3-ITD+ AML patients (n = 32), NPM1+ AML patients (n = 24), DNMT3A+ AML patients (n = 28). Results The average age of 25 DNMT3A/FLT3-ITD/NPM1 + patients was 46 years old, including 9 males and 16 females. Higher white blood cells (81.7×109/L) and bone marrow blasts (66.3 %) were found in DNMT3A/FLT3-ITD/NPM1+ group. The 3 years overall survival (3-OS) rate and 3 years disease free survival (3-DFS) rate in DNMT3A/FLT3-ITD/NPM1+ group were 17.65 % and 13.88 %, respectively. In DNMT3A/FLT3-ITD/NPM1+ group, 17 patients received chemotherapy as consolidation therapy, and 8 patients received allogeneic hematopoietic stem cell transplantation (HSCT). There were significant differences in 3-OS between DNMT3A/FLT3-ITD/NPM1+ group and FLT3-ITD+ group, NPM1+ AML group or DNMT3A+ group (DNMT3A+ group: P= 0.049 9, FLT3-ITD+ group: P = 0.036 1, NPM1+ group: P = 0.013 4), while no differences in 3-DFS were found (P > 0.05). Conclusions There are higher white blood cells and bone marrow blasts in DNMT3A/FLT3-ITD/NPM1+ CN-AML patients compared with those in FLT3-ITD+, NPM1+ AML or DNMT3A+ patients. DNMT3A/FLT3-ITD/NPM1+ CN-AML patients likely have the poor survival. Key words: DNMT3A mutation; FLT3-ITD mutation; NPM1 mutation; Leukemia, myeloid, acute; Clinical characteristics

NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematologic Malignancies

Minimal Residual Disease following Allogeneic Hematopoietic Stem Cell Transplantation

Maintenance Therapy in Patients with FLT3-ITD-Mutation-Positive Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation: Real-World Survival

Gemtuzumab Ozogamicin Plus Standard Induction Chemotherapy Improves Outcomes in Intermediate Risk Cytogenetic Acute Myeloid Leukemia

RUNX1 Mutation Does Not Significantly Impact the Outcome of Newly Diagnosedadult AML: A Retrospective Study of Chinese AML Patients

Hereditary Predisposition to Acute Myeloid Leukemia in Older Adults.

Nucleophosmin 1 (NPM1) mutations represent one of the most frequent genetic alterations in acute myeloid leukemia (AML). However, the prognostic significance of concurrent molecular abnormalities and clinical features in NPM1-mutated AML remains to be fully elucidated. We retrospectively analyzed 73 adult AML patients with NPM1 mutations. Clinical characteristics, molecular features, and treatment outcomes were evaluated. Comprehensive molecular profiling was performed to detect concurrent mutations. Survival analysis included recurrence-free survival (RFS) and overall survival (OS), with multivariate analysis to identify independent prognostic factors. The cohort showed a female predominance (54.8%), with a median age of 53.1 years. FLT3-ITD mutations were detected in 49.3% of patients, followed by DNMT3A (42.5%) and IDH1 (23.3%) mutations. Significant differences across FAB subtypes were observed in blast percentage (p = 0.003), WBC count (p = 0.013), and platelet count (p = 0.004). Multivariate analysis identified elevated WBC count (HR = 1.01, p = 0.008), increased LDH levels (HR = 1.0, p = 0.006), and FLT3-ITD mutations (HR = 2.55, p = 0.007) as independent adverse factors for RFS. For OS, low albumin levels (HR = 0.89, p = 0.017), DNMT3A mutations (HR = 2.49, p = 0.042), and treatment response were significant prognostic factors, while allogeneic hematopoietic stem cell transplantation showed a protective effect (HR = 0.08, p = 0.015). Our findings demonstrate that the clinical outcomes of NPM1-mutated AML are significantly influenced by concurrent molecular mutations and clinical parameters. The presence of FLT3-ITD and DNMT3A mutations, along with specific clinical features, identifies patients with adverse prognosis who might benefit from more intensive therapeutic strategies, including allogeneic transplantation.

Introduction The aim of the study was to determine molecular genetic and clinical characterization of acute myeloid leukemia (AML) with trisomy 8 as the sole chromosome abnormality, a recurrent but rare chromosomal abnormality in AML. Methods Interphase fluorescence in situ hybridization, reverse transcriptase-quantitative polymerase chain reaction for gene rearrangement and next-generation sequencing (NGS) were performed on sole trisomy 8 AML patients. Results A total of 35 AML patients with trisomy 8 as the sole chromosome abnormality were screened. The most frequently mutated genes were DNMT3A(37.1%), RUNX1(28.6%), FLT3-ITD(28.6%), IDH2(22.9%), NPM1(17.1%), and ASXL1 (14.3%). The sole +8 AML patients exhibited more mutations in RUNX1 (28.6% vs. 4.8%, P = 0.001) and ASXL1 (14.3% vs. 4.8%, P = 0.039) by comparing with normal karyotype AML (NK AML) patients(n = 63). The sole +8 AML patients(n = 35) with RUNX1 or IDH2 mutations showed significantly lower WBC counts, while FLT3-ITD showed higher white blood cell (WBC) counts as compared to the corresponding wild-type groups. Total of 45.7% patients achieved complete remission (CR) after the first induction therapy. The CR rate of patients with FLT3-ITD or IDH1 mutation was significantly lower than that in the corresponding wild-type cases (P = 0.047, 0.005, respectively). The median overall survival (OS) and disease-free survival (PFS) were 18.0 (95% CI: 10.8–25.2) and 10 (95% CI: 6.7–13.3) months, respectively. FLT3-ITD mutations and allogeneic hematopoietic stem cell transplantation (allo-HSCT) were independent prognostic markers for OS in multivariable analysis. Conclusion The results suggest a possible association between trisomy 8 and additional mutations that may influence clinical feature and prognosis.