Morphologic Dysplasia in De Novo Acute Myeloid Leukemia (AML) Is Related to Unfavorable Cytogenetics but Has No Independent Prognostic Relevance Under the Conditions of Intensive Induction Therapy: Results of a Multiparameter Analysis From the German AML Cooperative Group Studies

2003 ◽  
Vol 21 (2) ◽  
pp. 256-265 ◽  
Author(s):  
Torsten Haferlach ◽  
Claudia Schoch ◽  
Helmut Löffler ◽  
Winfried Gassmann ◽  
Wolfgang Kern ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
De Novo ◽  
World Health ◽  
Prognostic Impact ◽  
Cooperative Group ◽  
Prognostic Relevance ◽  
Health Organization ◽  
Acute Myeloid

Purpose: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification. Patients and Methods: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study. Results: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P < .001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P < .001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics. Conclusion: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account.

Clinico-pathologic characteristics and outcomes of the World Health Organization (WHO) provisional entity de novo acute myeloid leukemia with mutated RUNX1

2020 ◽  
Vol 33 (9) ◽  
pp. 1678-1689
Author(s):  
Andrés E. Quesada ◽  
Guillermo Montalban-Bravo ◽  
Rajyalakshmi Luthra ◽  
Keyur P. Patel ◽  
Koji Sasaki ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
World Health Organization ◽  
Myeloid Leukemia ◽  
De Novo ◽  
World Health ◽  
The World ◽  
Health Organization ◽  
Acute Myeloid

scholarly journals Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies

Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 551-558 ◽  
Author(s):  
Sabine Kayser ◽  
Manuela Zucknick ◽  
Konstanze Döhner ◽  
Jürgen Krauter ◽  
Claus-Henning Köhne ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
World Health ◽  
Prognostic Impact ◽  
Cytogenetic Abnormalities ◽  
Allogeneic Hsct ◽  
Monosomal Karyotype ◽  
Acute Myeloid

We aimed to determine the prognostic impact of monosomal karyotype (MK) in acute myeloid leukemia (AML) in the context of the current World Health Organization (WHO) classification and to evaluate the outcome of MK+ patients after allogeneic HSCT. Of 1058 patients with abnormal cytogenetics, 319 (30%) were MK MK+. MK+ patients were significantly older (P = .0001), had lower white blood counts (P = .0006), and lower percentages of BM blasts (P = .0004); MK was associated with the presence of −5/5q−, −7, 7q−, abnl(12p), abnl(17p), −18/18q−, −20/20q−, inv(3)/t(3;3), complex karyotype (CK), and myelodysplasia (MDS)–related cytogenetic abnormalities (P < .0001, each); and NPM1 mutations (P < .0001), FLT3 internal tandem duplications (P < .0001), and tyrosine kinase domain mutations (P = .02) were less frequent in MK+. Response to induction therapy and overall survival in MK+ patients were dismal with a complete remission rate of 32.5% and a 4-year survival of 9%. MK retained its prognostic impact in AML with CK, AML with MDS-related cytogenetic abnormalities, and in a revised definition (MK-R) excluding cases with recurrent genetic abnormalities according to WHO classification and those with derivative chromosomes not leading to true monosomies. In younger patients, allogeneic HSCT from matched related and unrelated donors resulted in a limited improvement of overall survival.

scholarly journals Germline CEBPA mutation in familial acute myeloid leukemia

2021 ◽  
Vol 13 (3) ◽  
Author(s):  
Matilde Boada ◽  
Ana Inés Catalan ◽  
Carolin Ottati ◽  
Florencia Bentancour ◽  
Daniela Lens ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Who Classification ◽  
World Health ◽  
Enhancer Binding Protein ◽  
History Of ◽  
Proper Diagnosis ◽  
Health Organization ◽  
Biallelic Mutations ◽  
Acute Myeloid

Myeloid Neoplasms with germline predisposition become part of 2016 World Health Organization (WHO) classification of hematological malignancies since 2016. CCAAT/enhancer binding protein-alpha (CEBPA) is a myeloid transcription factor located in chromosome 19q. Acute myeloid leukemia (AML) with biallelic mutations of CEBPA AML with recurrent genetic abnormalities according to WHO classification. The inheritance of a germline CEBPA mutation predisposes to the development of AML with autosomal dominant inheritance. Familial CEBPA AML share characteristics with somatic CEBPA AML. However, a higher relapse incidence is reported. We present the case of a 46-years-old male with family history of acute leukemia who was diagnosed with single mutated CEBPA acute myeloid leukemia. The same mutation was found in two of his siblings. The clinical suspicion and proper diagnosis of familial cases is necessary, especially when a related allogenic transplant is indicated in order to select an adequate donor.

The Value of CD64 Expression in Distinguishing Acute Myeloid Leukemia With Monocytic Differentiation From Other Subtypes of Acute Myeloid Leukemia: A Flow Cytometric Analysis of 64 Cases

2007 ◽  
Vol 131 (5) ◽  
pp. 748-754
Author(s):  
Cherie H. Dunphy ◽  
Wohzan Tang
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Flow Cytometric Analysis ◽  
World Health ◽  
Monocytic Differentiation ◽  
Flow Cytometric Immunophenotyping ◽  
Cd64 Expression ◽  
Flow Cytometric ◽  
Health Organization ◽  
Acute Myeloid

Abstract Context.—Flow cytometric immunophenotyping is a useful ancillary tool in the diagnosis and subclassification of acute myeloid leukemias (AMLs). A recent study concluded that CD64 is sensitive and specific for distinguishing AMLs with a monocytic component (ie, AML M4 and AML M5) from other AML subtypes. However, in that study, the intensity of CD64 was not well defined and the number of non-M4/non-M5 AMLs was small. Objective.—To evaluate the usefulness of CD64 by flow cytometric immunophenotyping in distinguishing AMLs with monocytic differentiation from other AML subtypes. Design.—Sixty-four AMLs subclassified based on the French-American-British and World Health Organization classifications on pretreatment bone marrows were retrieved from our files (7 M0s, 11 M1s, 17 M2s, 7 M3s, 9 M4s, 7 M5s, 4 M6s, and 2 M7s). A standard panel of markers, including CD2, CD3, CD5, CD7, CD10, CD11b, CD13, CD14, CD15, CD19, CD20, CD33, CD34, CD45, CD56, CD64, CD117, and HLA-DR, were analyzed by flow cytometric immunophenotyping in all AMLs (52 bone marrow samples; 12 peripheral blood samples). Results.—CD64 was expressed in AML subtypes M0 to M5 in varying intensities: heterogeneously expressed in 1 of 7 M0s; dimly expressed in 3 of 11 M1s; dimly and moderately expressed in 6 and 2 of 17 M2s, respectively; dimly and moderately expressed in 5 and 1 of 7 M3s, respectively; dimly expressed in 4 of 9 M4s; and heterogeneously, moderately, and strongly expressed in 1, 3, and 3 of 7 M5s, respectively. Conclusions.—Strong CD64 expression distinguishes AML M5; however, heterogeneous, dim, or moderate expression in itself does not distinguish M0 through M4 subtypes from M5 with dim to moderate CD64 expression. However, any CD64 expression associated with strong CD15 expression distinguishes AML M4 or M5, from other AML subtypes.

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.

Acute Myeloid Leukemia with Coexpression of Lymphoid-Associated Antigens: Clinicobiological Associations and Prognostic Implications,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3596-3596
Author(s):  
Georgia Voutiadou ◽  
Konstantina Kotta ◽  
Barbara Tachynopoulou ◽  
Apostolia Papalexandri ◽  
Chryssanthi Vadikolia ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Critical Role ◽  
Flow Cytometric Analysis ◽  
Prognostic Impact ◽  
Prognostic Implications ◽  
Cytogenetic Profile ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Abstract 3596 Immune phenotyping plays a critical role in the diagnosis and classification of acute leukemia. Several studies have reported a variable proportion of patients with acute myeloid leukemia (AML) expressing lymphoid-associated antigens (LAA). The exact frequency and true clinical significance of this phenomenon remains undefined due to inconsistencies between series, likely related to methodological aspects or potential case selection biases. We retrospectively evaluated the expression of LAA in blast cells from 278 consecutive and unselected patients with AML diagnosed in our Department between 2002 and 2010. The patient cohort included 168 males and 110 females with a median age of 61 years (range, 10–88); 146/278 cases were above the age of 60. Within this cohort, 190 cases (68%) had de novo AML, whereas the remaining 88 cases (32%) concerned secondary AML (sAML) to either MDS (n=80) or other non-hematologic malignancies (n=8). Patients were treated uniformly according to age with Aracytin/Idarubicin induction regimens (“3+7” or “2+5” for ages \q60 or ≥60, respectively). The immunophenotype was determined by flow cytometric analysis of (mainly) bone marrow aspirate and/or peripheral blood samples utilizing a primary CD45/side scatter (SSC) gating procedure with antibodies against CD7, CD13, CD19, CD33, CD4, CD10, CD34, CD117, CD64, HLA-DR, CD20, CD2, CD15, CD56, CD14, CD8, MPO, CD3, CD79a, CD22, TdT and lysozyme; a cut-off value for positivity of 20% was adopted. Overall, we identified 153/278 cases (55%) expressing at least one LAA. The most commonly expressed LAAs were CD4 (outside AML with monocytic differentiation), CD56, CD7, CD2, CD10 and CD79a (in 39%, 33%, 29%, 14%, 10% and 8% of LAA+ AML cases, respectively); interestingly, all CD79a-positive cases co-expressed at least one more LAA. A significant association was identified between LAA expression and cytogenetic profile: in particular, at least one LAA was detected in 37/50 cases (74%) with adverse cytogenetics (SWOG unfavorable and/or monosomal karyotype), compared to 24/41 (58%) cytogenetically favorable cases and 68/134 (51%) cytogenetically intermediate risk cases (p=0.01). No other statistically significant associations were found for LAA expression (positive vs. negative) in respect to age and complete remission (CR) rate. Furthermore, the frequency of LAA-positive cases was identical (55%) in both de novo AML (105/190 cases) and sAML (48/88 cases). Monoparametric statistical analysis was also performed individually for each of the six more frequent LAAs. Significant associations (p<0.05) were identified between: (i) CD7 expression and adverse cytogenetics; (ii) CD10 expression and adverse cytogenetics as well as failure to achieve CR, at both cohort level as well as patients \q60 years with de novo AML; and (iii) CD2 expression and shorter overall and disease-free survival (DFS and OS, respectively). Cox-multivariate analysis identified CD2 expression in addition to advanced age, sAML and adverse cytogenetic profile as negative prognostic indicators (p=0.05) for both DFS and OS. In conclusion, expression of LAAs is frequent in AML, among both de novo AML and sAML cases, and significantly associated with adverse cytogenetics. Although the negative prognostic impact of CD2 expression is noteworthy, however, the precise prognostic implications of the expression of individual LAAs are hard to define on single institution retrospective series and will require evaluation in large prospective and well-controlled studies. Disclosures: No relevant conflicts of interest to declare.

The Size of the Dendritic Cell Population At Diagnosis Worsens Prognosis in Acute Myeloid Leukemia – Bigger Is Not Better

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4870-4870
Author(s):  
Marta I Pereira ◽  
Ana I Espadana ◽  
Emília Cortesão ◽  
Gilberto P Marques ◽  
Catarina Geraldes ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
World Health ◽  
Biological Behavior ◽  
Newly Diagnosed ◽  
Secondary Aml ◽  
De Novo Aml ◽  
Dc Component ◽  
Acute Myeloid

Abstract Abstract 4870 Background: Dendritic cells (DC) are a heterogeneous population of lineage-negative antigen-presenting cells derived from CD34+ hematopoietic progenitors, present in tissue, blood and bone marrow (BM), where plasmacytoid DC (pDC) are a normal finding, representing 0.2 ± 0.1% of cell populations (Matarraz et al, 2010). DC neoplasms include solid tumors (such as DC sarcomas) and an entity classified by the World Health Organization (2008) as an acute myeloid leukemia (AML)-related precursor neoplasm: blastic pDC neoplasm/leukemia, an aggressive disease with poor prognosis, with no clinical trials to orient consensus regarding the most effective treatment; it is usually chemo-resistant, although some cases respond to AML-like regimens and allogeneic hematopoietic stem cell transplant. It is not clear if the presence of an increased DC population in non-DC AML confers pDC neoplasm-like biological characteristics to the former. Aims: This study aims to evaluate whether an increase in the size of DC populations in newly-diagnosed non-DC AML affects the latter's biological behavior, as represented by the overall survival (OS) of patients with the disease. Methods: We reviewed all AML diagnosed in our Hospital between January 1st 2008 and December 31st 2010, identifying 146 patients. We excluded 9 patients who had no flow cytometry immunophenotyping (IP) performed, and 7 whose first IP was performed after treatment was instituted. In that time frame, we also diagnosed 4 pDC neoplasms. Of the 130 patients included, 91 had their presenting IP performed on BM aspirate, while the remaining 39 were phenotyped on blood samples. The size of the DC populations and blastic DC maturation were determined on these samples. Patients were classified into 2 groups according to the size of the DC component; one (the Non-DC Group) had a DC component of up to 0.3% (in practice, the highest value in this group was 0.2%); the other (DC Group) had a percentage over this limit (the lowest value being 1.0%). OS data was determined for both groups; special consideration was given to age strata, separating patients under 65 years of age (Under-65) from those 65 or older (Over-65) and etiology (distinguishing de novo AML from AML secondary to therapy, myelodysplasia or myeloproliferative diseases). The percentage of DC identified by IP did not influence nor alter the type of treatment instituted. Results: We found that the presence of a DC component above the normal BM interval (as determined by Matarraz et al) was associated with a significantly decreased OS, with patients with DC components over 0.3% presenting with a median OS of 2.4 months (mean: 6.4 ± 1.6) and those with a component under 0.3% with a median OS of 8.6 months (mean: 17.0 ± 1.9) (p = 0.033). In our series, patients Over-65 had a median OS of 2.9 months (mean = 6.9 ± 1.0) and those Under-65 a median of 21.3 months (mean = 22.5 ± 2.5), p < 0.001. The differences in OS according to DC component were attenuated in patients Over-65 (median = 1.8 vs. 3.9 months, p = NS), whereas in patients Under-65 the median survival was 2.7 months (mean: 8.7 ± 2.9) for the DC Group and 24.4 months (mean: 24.3 ± 2.7) for the non-DC Group (p = 0.035). The differences in OS were also significant for de novo AML (median = 2.4 vs. 16.0 months, mean = 4.7 ± 1.9 vs. 20.5 ± 2.6, p = 0.017), but not statistically relevant for secondary AML (median = 4.4 vs. 5.5 months, mean = 8.4 vs. 10.8, p = NS). Discussion: In this study, we found that an increase in the size of the DC component as determined by IP at diagnosis on newly-diagnosed AML had a negative impact on prognosis, with a significant decrease in median and mean OS in patients with a percentage of DC over the upper limit of the normal interval. We also determined that the decreased survival was primarily attributed to the better-prognosis groups (patients under 65 and with de novo AML), whereas the effect of the worsened prognosis was attenuated in those patients with a bad prognosis at the outset (patients over 65 and with secondary AML). If data from DC neoplasms could be extrapolated, we could suggest that AML with increased DC components are less chemo-sensitive, which would explain the OS differences found in the Under-65 group, as well as the no-difference found in the Over-65 Group, which is frequently undertreated due to comorbidities. Conclusion: Our study suggests that the size of the DC component at diagnosis as determined by IP is a new prognostic marker predictive of decreased survival. Disclosures: No relevant conflicts of interest to declare.

EZH2 Mutations Are Associated with Low Blast Percentage in Bone Marrow and −7/Del(7q) Karyotype in De Novo Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2544-2544
Author(s):  
Xiuli Wang ◽  
Haiping Dai ◽  
Qian WANG ◽  
Qinrong Wang ◽  
Yang Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Myelogenous Leukemia ◽  
Prognostic Impact ◽  
Coding Region ◽  
Acute Myeloid

Abstract Abstract 2544 Somatic mutation of the EZH2 gene is seen in myelodisplastic syndrome, myelofibrosis, and chronic myelomonocytic leukemia patients. The prevalence and prognostic impact of somatic mutations of EZH2 in patients with acute myelogenous leukemia (AML) remains unknown. In this study, we sought to determine the incidence and clinical implications of somatic EZH2 mutations in 714 patients with de novo AML by PCR amplification of the entire coding region followed by direct bidirectional DNA sequencing. EZH2 mutations were identified in 13/714 (1.8%) of AML patients and occurred almost exclusively in males (11/13, P=0.033). In univariate analysis, the presence of EZH2 mutations was significantly associated with lower blast percentage (21–30%) in bone marrow (P=0.0001) and −7/del(7q) (P=0.025). There was no difference in the incidence of mutations in 13 genes, including ASXL1, CBL, c-KIT, DNMT3A, FLT3, IDH1, IDH2, MLL, NPM1, NRAS, RUNX1, TET2, and WT1, between patients with and without EZH2 mutations. Complete remission, event-free survival or overall survival was similar between AML patients with and without EZH2 mutation (p>0.05). These results demonstrated EZH2 mutation as a recurrent genetic abnormality associated with lower blast percentage in BM and −7/del(7q) in de novo acute myeloid leukemia. Disclosures: No relevant conflicts of interest to declare.

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.

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