Incidence, Survival, and Risk Factors for Adults with Acute Myeloid Leukemia Not Otherwise Specified and Acute Myeloid Leukemia with Recurrent Genetic Abnormalities: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database, 2001–2013

2018 ◽  
Vol 139 (2) ◽  
pp. 115-127 ◽  
Author(s):  
Xiaolu Song ◽  
Ye Peng ◽  
Xiaogang Wang ◽  
Yirui Chen ◽  
Lai Jin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Classification Systems ◽  
Seer Database ◽  
Risk Of Death ◽  
Not Otherwise Specified ◽  
Genetic Abnormalities ◽  
Acute Myeloid ◽  
End Results

Background/Aim: As the knowledgebase of acute myeloid leukemia (AML) has grown, classification systems have moved to incorporate these new findings. Methods: We assessed 32,941 patients with AML whose records are contained in the Surveillance, Epidemiology, and End Results (SEER) database. Results: Half of all patients diagnosed between 2001 and 2013 did not have a World Health Organization (WHO) classification. Acute promyelocytic leukemia and acute panmyelosis with myelofibrosis were associated with the longest leukemia-specific survival (110 and 115 months, respectively), and AML with minimal differentiation and acute megakaryoblastic leukemia with the shortest (30 and 28 months, respectively). For patients in the WHO groups AML not otherwise specified (AML-NOS) and AML with recurrent genetic abnormalities (AML-RGA), the risk of death was greater for older patients and less for married patients. Black patients with any type of AML-NOS also had a higher risk of death. Patients whose case of AML did not receive a WHO classification were older and this group had a higher risk of death when compared to patients with a WHO type of AML-NOS. Conclusion: Our findings highlight the divergent outcomes of patients with AML and the importance of using the WHO classification system and demographic factors to gauge their prognosis.

Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system

Blood ◽  
2009 ◽  
Vol 113 (9) ◽  
pp. 1906-1908 ◽  
Author(s):  
Olga K. Weinberg ◽  
Mahesh Seetharam ◽  
Li Ren ◽  
Katie Seo ◽  
Lisa Ma ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Progression Free Survival ◽  
World Health ◽  
Multilineage Dysplasia ◽  
Molecular Features ◽  
Not Otherwise Specified ◽  
Cebpa Mutations ◽  
Acute Myeloid

Although some studies have validated the 2001 World Health Organization (WHO) classification of acute myeloid leukemia (AML), including the importance of multilineage dysplasia, others have suggested that multilineage dysplasia correlates with unfavorable cytogenetics but has no independent impact on prognosis. In 2008, the revised WHO classification has expanded this category into “AML with myelodysplasia-related changes” (AML-MRC). We evaluated the clinical, pathologic, cytogenetic, and molecular features of 100 AML patients using the 2008 WHO criteria. Patients underwent genetic screening for NPM1, FLT3-ITD, FLT3-D835, and CEBPA mutations. Compared with patients with AML, not otherwise specified, patients with AML-MRC were significantly older (P = .014), presented with a lower hemoglobin (P = .044), more frequently expressed CD14 (P = .048), and exhibited a decreased frequency of CEBPA mutations (P = .001). Multivariate analysis indicated that patients with AML-MRC had a significantly worse overall survival, progression-free survival, and complete response compared with AML-not otherwise specified (all P < .001). These data support the clinical, morphologic, and cytogenetic criteria for this 2008 WHO AML category.

The Genotype Consisting of Complex Karyotype and TP53 Gene Mutation Is Specific to Acute Myeloid Leukemia with Multilineage Dysplasia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2507-2507
Author(s):  
Yuichi Ishikawa ◽  
Hitoshi Kiyoi ◽  
Akane Tsujimura ◽  
Yasushi Miyazaki ◽  
Masao Tomonaga ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Tp53 Mutation ◽  
Genetic Alterations ◽  
Chromosome 17 ◽  
Complex Karyotype ◽  
Genetic Abnormalities ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous disorder of hematopoietic progenitor cells. The World Health Organization (WHO) classification of the myeloid neoplasm incorporates genetic, immunophenotypic, biologic and clinical features. Although the WHO classification recognizes several chromosomal translocations they are frequently seen in AML patients, for categorizing the AML with recurrent genetic abnormalities, a number of other genetic alterations such as point mutations and gene rearrangements have not been included. To date, several genetic alterations, which are involved in the pathogenesis of AML and associated with prognosis of patients, have been documented. Therefore, it is required to establish the detailed classification of AML according to the genetic status. In this study, we comprehensively analyzed the genetic alterations and in de nove AML patients and investigated the association with mutational status, cytogenetic status and clinical features in comparison with the WHO classification. The study population included 144 newly diagnosed de nove AML patients consisting of 38 recurrent genetic abnormalities (RGA), 34 multilineage dysplasia (MLD) and 72 not otherwise categorized (NOC) according to WHO subcategories. Bone marrow samples were obtained from the patients after obtaining informed consent for banking and molecular analyses. Mutations in FLT3, cKIT, NPM1, N-RAS, TP53, C/EBPA, AML1, WT1 and MLL/PTD were analyzed as previously described. In consistent with previous reports, FLT3 (24%), cKIT (5%), NPM1 (20%), N-RAS (8%), C/EBPA (12%), AML1 (2%), MLL-PTD (9%), WT1 (3%) and TP53 (8%) mutations were frequently observed. No significantly different distribution was found in the prevalence of FLT3, N-RAS, C/EBPA, AML1 and MLL-PTD mutations among the WHO categories. However, the skewed prevalence was found in cKIT, NPM1 and TP53 mutations: cKIT mutation was frequently found in AML-RGA, NPM1 mutation was not found in AML-RGA, and TP53 mutation was preferentially found in AML-MLD. N-RAS, C/EBPA, AML1 and WT1 mutations were not identified in AML-RGA, though their distributions were not statistically significant among the WHO categories. It is notable that 9 of 12 (75%) patients who have TP53 mutation are categorized in AML with MLD and 8 of the 9 have complex-karyotype. Importantly, 8 of 9 (88.9%) showed complex karyotype, and 5 of them deleted chromosome 17. In this study, we found 2 additional patients harboring TP53 mutation in the other categories, while they did not show the complex karyotype and chromosome 17 abnormality. Furthermore, complex karyotype was found in 14 of the 144 entire AML patients, while 10 of them were categorized in AML-MLD. The remaining 4 patients were categorized in AML-NOC. Three of them showed del(17) or del(17p), though TP53 mutation was not identified. The genotype consisting of complex karyotype and TP53 mutation was, therefore, specifically found in AML-MLD. Thus TP53 mutation and complex-karyotype AML are significantly correlated and associated with the presence of multi-lineage dysplasia (P= .000 and P= .000, respectively). Moreover, these patients have significantly inferior induction rate and overall survival in AML with MLD. These results suggest that TP53 mutation and complex-karyotype AML distinguish a disease entity in AML with MLD.

Clinicopathologic Characterization of Acute Myeloid Leukemia and Myelodysplastic Syndrome with Inv(3)(q21q26.2)/t(3;3)(q21;q26.2) Reveals That Complex Karyotype but Not Blast Percentage Is Associated with Poor Survival; A Bone Marrow Pathology Group Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3847-3847
Author(s):  
Heesun J. Rogers ◽  
James W. Vardiman ◽  
John Anastasi ◽  
Gordana Raca ◽  
Natasha M Savage ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Risk Group ◽  
Risk Groups ◽  
Complex Karyotype ◽  
Genetic Abnormalities ◽  
Very High ◽  
Acute Myeloid

Abstract Abstract 3847 Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2); RPN1-EVI1 [inv3/t3] is a distinct type of AML with recurrent genetic abnormalities (RGA) in the 2008 WHO classification, with poor response to therapy and poor prognosis. The resulting dysregulation of EVI1 plays an important role in stem cell self-renewal and leukemogenesis. Although myelodysplastic syndrome (MDS) with inv3/t3 has a high risk of progression to AML, inv3/t3 is not among the genetic abnormalities sufficient for diagnosis of AML, irrespective of blast percentage (%) in the WHO classification. The revised International Prognostic Scoring System (IPSS-R) includes comprehensive cytogenetic subgrouping to better define prognosis in MDS patients. In this system, inv3/t3 is included in a poor risk karyotype group. The objective of this multicenter study was to evaluate a series of patients with MDS/AML and inv3/t3 in order to characterize their clinicopathologic features and outcome, and to apply the IPSS-R to inv3/t3 MDS patients. 111 patients (40 MDS and 71 AML with inv3/t3) were gathered from 8 medical centers. The median age at diagnosis was 56.5 years and was significantly older in MDS than AML with inv3/t3 patients (65 vs 54.5, p=0.03). Patients typically presented with normocytic anemia, thrombocytopenia and mild leukopenia (median Hb 9.1 g/dL, platelet 91 x109/L, WBC 3.6 x109/L). MDS with inv3/t3 patients had lower WBC than AML with inv3/t3 (median 3.1 vs 5.5, p<0.001). 19% of patients had hepatosplenomegaly. The median bone marrow (BM) blast% was 4% in MDS and 50% in AML with inv3/t3 and BM cellularity was higher in AML (70%) than MDS (40%) with inv3/t3 (both p<0.001). 88% of patients showed dysmegakaryopoiesis with characteristic small uni/bilobated forms. Dysgranulopoiesis (46%) and dyserythropoiesis (56%) were common and 59% of patients displayed multilineage dysplasia. The cytogenetics showed isolated inv3/t3 in 41% of patients, one additional abnormality in 33% and complex karyotype in 26%. −7/del7q (37%) was a frequent additional abnormality. Philadelphia chromosome (Ph) was noted in 10% of AML with inv3/t3. Overall 83% of patients (75% of MDS and 87% of AML with inv3/t3) expired (median follow up of 7.9 months (mo)). Most patients received therapy including 54% with chemotherapy (CTX; topoisomerase II inhibitors and/or antimetabolites) alone, 27% with CTX and allogeneic stem cell transplant (SCT) and 19% with supportive care. 16% of patients (10 MDS and 8 AML with inv3/t3) were associated with prior therapy for solid tumors and lymphomas. 57% of MDS with inv3/t3 patients subsequently evolved to AML. There was no significant difference in overall survival (OS) between MDS and AML with inv3/t3 (12.9 vs 8.0 mo, Cox PH p=0.11, Figure 1). There was no OS difference between MDS and AML after excluding Ph+ cases (Cox PH p=0.17) nor between de novo and therapy related MDS/AML with inv3/t3 (Cox PH p=0.89). Patients with isolated inv3/t3, one additional cytogenetic abnormality, and a complex karyotype showed progressively shorter OS (12.9, 10.0 and 4.3 mo, Cox PH p<0.001, Figure 2). The patients who received CTX and SCT showed superior OS to patients receiving CTX alone or supportive care only (15, 7 and 5 mo, respectively, Cox PH p=0.02). In multivariate analysis, choice of therapy and complex karyotype retained independent prognostic significance (Cox PH p= 0.02 and p<0.001, respectively). MDS with inv3/t3 patients were classified into IPSS Intermediate (Int)-1 (21), Int-2 (13), and high (6) risk groups. IPSS-R categorized MDS patients into low (3), Int (6), high (14) and very high (17) risk groups. 57% of IPSS Int-1 risk group patients (expected OS 3.5 year) were reclassified to high or very high risk group in IPSS-R (expected OS <1.6 year). Thus, the IPSS-R scores were higher relative to IPSS score (signed rank test, P<0.001). However, 72.5% and 77.5% of MDS with inv3/t3 patients had shorter OS than expected OS by IPSS-R and IPSS scores. The IPSS-R better reflects the OS of inv3/t3 than IPSS but may not fully reflect the generally dismal prognosis. Patients with MDS and AML with inv3/t3 follow a similarly aggressive clinical course, supporting classification of MDS with inv3/t3 as an AML with RGA irrespective of blast%. Additional cytogenetic abnormalities are associated with shorter OS in AML/MDS with inv3/t3 and our data suggest that aggressive therapy with SCT should be considered in these patients. Disclosures: Vardiman: Celgene Corporation: review of slides for clinical trials not relevant to this abstract Other. Foucar:e. Honoraria–Scientific Symposium Pathology Education: ASCP Press; ARP, Amirsys, ASCP Press; ARP, Amirsys Patents & Royalties, Honoraria, Not relevant to this abstract Other.

Comprehensive Analysis of Genetic Alterations in Acute Myeloid Leukemia According to the WHO Classification.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4311-4311
Author(s):  
Yuichi Ishikawa ◽  
Hitoshi Kiyoi ◽  
Akane Tsujimura ◽  
Yasusi Miyazaki ◽  
Masao Tomonaga ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Normal Karyotype ◽  
Genetic Alterations ◽  
P53 Mutation ◽  
Npm1 Mutation ◽  
Multilineage Dysplasia ◽  
Genetic Abnormalities ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic progenitor cells, and is thought to be the consequence of two broad complementation classes of mutations: those that confer a proliferative and/or survival advantage to hematopoietic progenitors, and those that impair hematopoietic differentiation and confer properties of self-renewal. To date, several genetic alterations, which are involved in the pathophysiology of the AML development, have been apparent, and some of them have been disclosed to have an impact on the clinical management. Therefore, it is required to establish the detailed classification of AML according to the genetic status. In this study, we comprehensively analyzed the genetic alterations in AML patients in comparison with the WHO classification. The study population included 115 newly diagnosed AML patients consisting of 25 recurrent genetic abnormalities, 25 multilineage dysplasia, 7 therapy-related and 56 not otherwise categorized WHO subcategories. Bone marrow samples were obtained from the patients after obtaining informed consent for banking and molecular analyses. Mutations in FLT3, cKIT, NPM1, N-RAS, p53, C/EBPa, AML1 and AKT1 genes were analyzed as previously described. In consistent with previous reports, FLT3 (20.9%), NPM1 (14.8%) and C/EBPa (13.0%) mutations were frequently observed, while no AKT1 mutation was found. Furthermore, NPM1 mutation was not found in AML with recurrent genetic abnormalities and C/EBPa mutation was not found in AML with recurrent genetic abnormalities or therapy related. Nine cases have double mutations of FLT3 and NPM1 genes, and 3 have FLT3 and C/EBPa mutations. Of note is that 15 of 25 (60%) AML with multilineage dysplasia cases have at least one mutation in p53, NPM1, C/EBPa, FLT3, N-RAS and AML1 genes and that p53 mutation was selectively found in the cases with complex karyotype. However, 4 AML with multilineage dysplasia cases with normal karyotype did not have any mutations in the analyzed genes. Comprehensive genetic analysis clarifies the detailed molecular base of AML and could make the subdivision of the WHO classification by combining the analysis for clinical impacts. Especially, mutation status in p53, NPM1 and C/EBPa genes seems to be useful for the subdivision of the AML with multilineage dysplasia, which is the most heterogeneous subcategory in the WHO classification.

scholarly journals Population-based disparities in survival among patients with core-binding factor acute myeloid leukemia: A SEER database analysis

2014 ◽  
Vol 38 (7) ◽  
pp. 773-780 ◽  
Author(s):  
Andrew M. Brunner ◽  
Traci M. Blonquist ◽  
Hossein Sadrzadeh ◽  
Ashley M. Perry ◽  
Eyal C. Attar ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Population Based ◽  
Seer Database ◽  
Database Analysis ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Acute Myeloid

Acute Leukemia

2016 ◽  
Author(s):  
Richard A. Larson ◽  
Roland B Walter
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
Lymphoblastic Leukemia ◽  
World Health ◽  
Acute Leukemias ◽  
Acute Myeloid

The acute leukemias are malignant clonal disorders characterized by aberrant differentiation and proliferation of transformed hematopoietic progenitor cells. These cells accumulate within the bone marrow and lead to suppression of the production of normal blood cells, with resulting symptoms from varying degrees of anemia, neutropenia, and thrombocytopenia or from infiltration into tissues. They are currently classified by their presumed cell of origin, although the field is moving rapidly to genetic subclassification. This review covers epidemiology; etiology; classification of leukemia by morphology, immunophenotyping, and cytogenetic/molecular abnormalities; cytogenetics of acute leukemia; general principles of therapy; acute myeloid leukemia; acute lymphoblastic leukemia; and future possibilities. The figure shows the incidence of acute leukemias in the United States. Tables list World Health Organization (WHO) classification of acute myeloid leukemia and related neoplasms, expression of cell surface and cytoplasmic markers for the diagnosis of acute myeloid leukemia and mixed-phenotype acute leukemia, WHO classification of acute lymphoblastic leukemia, WHO classification of acute leukemias of ambiguous lineage, WHO classification of myelodysplastic syndromes, European LeukemiaNet cytogenetic and molecular genetic subsets in acute myeloid leukemia with prognostic importance, cytogenetic and molecular subtypes of acute lymphoblastic leukemia, terminology used in leukemia treatment, and treatment outcome for adults with acute leukemia. This review contains 1 highly rendered figure, 9 tables, and 117 references.

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