Normal Karyotype-Acute Myeloid Leukemia With The CD4- CD7+ CD15+ CD34+ Immunophenotype Is a Clinically Distinct Entity With a Favorable Outcome

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2608-2608
Author(s):  
Noriyoshi Iriyama ◽  
Norio Asou ◽  
Toru Sakura ◽  
Tomoya Maeda ◽  
Hiroshi Handa ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Surface Antigen ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Antigen Expression ◽  
Free Survival ◽  
Surface Antigen Expression ◽  
Prognostic Implications ◽  
Acute Myeloid

Abstract Background Immunophenotyping is a standard diagnostic procedure in leukemia, but unlike cytogenetic classifications, which are reliable indicators for prognostic interpretation, immunophenotyping has, thus far, yielded inconsistent results. Recently, the presence of CEBPA, NPM1, or FLT3 mutations, as a molecular characteristic, was identified as an important prognostic factor for normal karyotype (NK)-acute myeloid leukemia (AML). Because AML with the CEBPA mutation is closely associated with specific surface antigen expression, we investigated the prognostic implications and characteristics of a certain immunophenotype in NK-AML. Design and Methods The frequency of CEBPA mutation according to cytogenetic classification in 318 AML patients was investigated, and then the surface antigen expression profile in NK-AML was assessed. Thereafter, the prognosis and patient characteristics of a specific immunophenotype was investigated in 329 NK-AML patients from the Japan Adult Leukemia Study Group (JALSG) AML97 study. Factor differences between groups of patients with and without this immunophenotype were compared by Fisher’s exact and Student’s t-tests. Complete remission (CR), disease-free survival (DFS), event-free survival (EFS) and overall survival (OS) was assessed using Fisher’s exact and log-rank tests. We used a multivariate Cox proportional hazard regression model to assess factors that could possibly affect the clinical outcome. Results The CEBPA mutation, including 12 monoallelic and 29 biallelic mutations, was detected in 41 of the 318 AML patients. AML with the CEBPA mutation was frequently observed in NK-AML and in cytogenetically intermediate-risk AML, but rare in favorable- or adverse-risk AML. NK-AML with the CEBPA mutation was closely associated with CD4 negativity as well as CD7 and CD34 positivity in 133 NK-AML cases. Furthermore, CD15 positivity is known to be associated with the CEBPA mutation. Therefore, we investigated the prognostic implications and characteristics of the CD4- CD7+ CD15+ CD34+ immunophenotype in NK-AML in the JALSG AML97 study. NK-AML with the CD4- CD7+ CD15+ CD34+ immunophenotype was classified as the CEBPA type, and NK-AML without this immunophenotype was considered as the non-CEBPA type. Of the 329 NK-AML patients analyzed, 39 and 243 were classified as having CEBPA and non-CEBPA type NK-AML, respectively. NK-AML patients with CEBPA type tended to have better EFS and OS than those with non-CEBPA type (5-year EFS, 48.4% vs 30.6%, P = 0.039; 5-year OS, 67.3% vs 35.7%, P = 0.0019). Multivariate analysis showed that the CEBPA type and white blood cell (WBC) counts of >20 × 109/L were independent prognostic factors for better EFS and OS. Compared to non-CEBPA type NK-AML, CEBPA type was associated with higher MPO-positive rates, frequent presentation with Auer rods, and a FAB classification of M1 or M2. Conclusions NK-AML with the CD4- CD7+ CD15+ CD34+ immunophenotype is a clinically discrete entity, indicating the presence of the CEBPA mutation, which may have a possible role in risk stratification. Disclosures: Taniwaki: Novartis: Honoraria.

Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1997-2004 ◽  
Author(s):  
G Del Poeta ◽  
R Stasi ◽  
G Aronica ◽  
A Venditti ◽  
MC Cox ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Free Survival ◽  
Negative Phenotype ◽  
Acute Myeloid

Abstract Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

scholarly journals Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1997-2004 ◽  
Author(s):  
G Del Poeta ◽  
R Stasi ◽  
G Aronica ◽  
A Venditti ◽  
MC Cox ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Free Survival ◽  
Negative Phenotype ◽  
Acute Myeloid

Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

scholarly journals Clinical significance of surface antigen expression in children with acute myeloid leukemia: results of study AML-BFM-87

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3097-3108 ◽  
Author(s):  
U Creutzig ◽  
J Harbott ◽  
C Sperling ◽  
J Ritter ◽  
M Zimmermann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Surface Antigen ◽  
Cytosine Arabinoside ◽  
Myeloid Leukemia ◽  
Antigen Expression ◽  
Diagnostic Value ◽  
High Dose ◽  
Cell Surface Antigens ◽  
Surface Antigen Expression ◽  
Acute Myeloid

Abstract Immunophenotyping using a panel of 15 antibodies was performed in 267 (87%) and cytogenetic analysis in 196 (64%) of 307 children under 17 years of age enrolled in the AML-BFM-87 study. Treatment consisted of cytosine arabinoside, daunorubicin, etoposide induction and a 6-week seven-drug consolidation chemotherapy, followed by two blocks of high-dose cytosine arabinoside with or without cranial irradiation and maintenance therapy for 1 year. Five-year event-free survival for patients with immunophenotypic data was .43 +/- .03 SE. The diagnostic value of the pan-myeloid reagents CD13, CD33, and CDw65 for the recognition of childhood acute myeloid leukemia (AML) was high with a sensitivity of 98% (positivity of at least one of these antigens), whereas, with the exception of CD41 for French American British (FAB) subtype M7, the expression of single cell-surface antigens showed no correlation with morphologic or cytogenetic subgroups. On the other hand, characteristic subgroups of AML defined by morphologic features and karyotypes could be described by low or high rates of surface antigen expression compared with those of other patients. These immunophenotypic features most probably associated with specific entities include expression of CD34 or CD13 and absence of CD14 or CD4 in M2 with Auer rods/t(8;21); absence of HLA-DR, CD34, and CD14, but expression of CD33 in M3/t(15;17); positivity of either CD34 or CD13 and either CD14 or CD2 for M4Eo/inv(16); and absence of either CD34 or CD13 and expression of either CD33 or CDw65 and either CD15 or CD4 for M5/t(9;11). In FAB M0, negativity of one or two of the three panmyeloid-associated markers (CD13/33/w65) was common; and cytogenetic results frequently showed random abnormalities. Expression of lymphoid-, progenitor- and most myeloid-associated antigens had no influence on the prognosis, whereas the outcome was significantly better for children with M2 with Auer rods, M3, or M4Eo or for those with the associated karyotypes t(8;21);t(15;17) and inv(16) than for other patients.

Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML)

Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 4011-4020 ◽  
Author(s):  
Christian Thiede ◽  
Sina Koch ◽  
Eva Creutzig ◽  
Christine Steudel ◽  
Thomas Illmer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
Clinical Impact ◽  
Prognostic Impact ◽  
Npm1 Mutation ◽  
Free Survival ◽  
High Bone ◽  
Acute Myeloid

Mutations of the nucleophosmin (NPM1) gene have recently been described in patients with acute myeloid leukemia (AML). To clarify the prevalence as well as the clinical impact of this mutation, we investigated 1485 patients with AML for NPM1 exon 12 mutations using fragment analysis. A 4 bp insert was detected in 408 of 1485 patients (27.5%). Sequence analysis revealed known mutations (type A, B, and D) as well as 13 novel alterations in 229 analyzed cases. NPM1 mutations were most prevalent in patients with normal karyotype (NK) (324 of 709; 45.7%) compared with 58 of 686 with karyotype abnormalities (8.5%; P < .001) and were significantly associated with several clinical parameters (high bone marrow [BM] blasts, high white blood cell [WBC] and platelet counts, female sex). NPM1 alterations were associated with FLT3-ITD mutations, even if restricted to patients with NK (NPM1-mut/FLT3-ITD: 43.8%; versus NPM1-wt/FLT3-ITD: 19.9%; P < .001). The analysis of the clinical impact in 4 groups (NPM1 and FLT3-ITD single mutants, double mutants, and wild-type [wt] for both) revealed that patients having only an NPM1 mutation had a significantly better overall and disease-free survival and a lower cumulative incidence of relapse. In conclusion, NPM1 mutations represent a common genetic abnormality in adult AML. If not associated with FLT3-ITD mutations, mutant NPM1 appears to identify patients with improved response toward treatment.

scholarly journals Clinical significance of surface antigen expression in children with acute myeloid leukemia: results of study AML-BFM-87

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 3097-3108 ◽  
Author(s):  
U Creutzig ◽  
J Harbott ◽  
C Sperling ◽  
J Ritter ◽  
M Zimmermann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Surface Antigen ◽  
Cytosine Arabinoside ◽  
Myeloid Leukemia ◽  
Antigen Expression ◽  
Diagnostic Value ◽  
High Dose ◽  
Cell Surface Antigens ◽  
Surface Antigen Expression ◽  
Acute Myeloid

Immunophenotyping using a panel of 15 antibodies was performed in 267 (87%) and cytogenetic analysis in 196 (64%) of 307 children under 17 years of age enrolled in the AML-BFM-87 study. Treatment consisted of cytosine arabinoside, daunorubicin, etoposide induction and a 6-week seven-drug consolidation chemotherapy, followed by two blocks of high-dose cytosine arabinoside with or without cranial irradiation and maintenance therapy for 1 year. Five-year event-free survival for patients with immunophenotypic data was .43 +/- .03 SE. The diagnostic value of the pan-myeloid reagents CD13, CD33, and CDw65 for the recognition of childhood acute myeloid leukemia (AML) was high with a sensitivity of 98% (positivity of at least one of these antigens), whereas, with the exception of CD41 for French American British (FAB) subtype M7, the expression of single cell-surface antigens showed no correlation with morphologic or cytogenetic subgroups. On the other hand, characteristic subgroups of AML defined by morphologic features and karyotypes could be described by low or high rates of surface antigen expression compared with those of other patients. These immunophenotypic features most probably associated with specific entities include expression of CD34 or CD13 and absence of CD14 or CD4 in M2 with Auer rods/t(8;21); absence of HLA-DR, CD34, and CD14, but expression of CD33 in M3/t(15;17); positivity of either CD34 or CD13 and either CD14 or CD2 for M4Eo/inv(16); and absence of either CD34 or CD13 and expression of either CD33 or CDw65 and either CD15 or CD4 for M5/t(9;11). In FAB M0, negativity of one or two of the three panmyeloid-associated markers (CD13/33/w65) was common; and cytogenetic results frequently showed random abnormalities. Expression of lymphoid-, progenitor- and most myeloid-associated antigens had no influence on the prognosis, whereas the outcome was significantly better for children with M2 with Auer rods, M3, or M4Eo or for those with the associated karyotypes t(8;21);t(15;17) and inv(16) than for other patients.

scholarly journals Characteristics and Survival of 927 Moroccan Adults with Acute Myeloid Leukemia: Monocentric Experience

2021 ◽  
Vol 6 (1) ◽  
pp. 5-13
Author(s):  
Oum kaltoum Ait boujmia ◽  
Mona Lamchahab ◽  
Nezha Hda ◽  
Asma Quessar
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Group Versus ◽  
Disease Free Survival ◽  
Normal Karyotype ◽  
P Value ◽  
Balanced Translocation ◽  
Free Survival ◽  
Disease Free ◽  
Acute Myeloid

Acute myeloïd leukemia (AML) is the most frequent form of acute leukemia among adults and the most aggressive type of leukemia, which is associated with the lowest survival rate. Patients with AML are treated with intensive chemotherapy and many factors could influence the survival of these patients, such as age, cytogenetic abnormalities; white blood cell (WBC) counts. The aim of this work was to study the epidemiological and response profiles of AML adults patients in Morocco.Patients and Methods: A prospective, descriptive study conducted in the Hematology and Pediatric Oncology department, 20 August Hospital Casablanca, and concerned adult patients diagnosed with AML through a period of seven years (January 2011 to December 2017). Statistical analysis was performed using SPSS version 20. The overall survival and disease-free survival were evaluated by using the Kaplan–Meier method. Results: A total of 927 patients diagnosed with AML during the 7 year period. 466 (50.3%) were males and 461 (49.7%) were females. The median age of patients was 46years.The most represented age group was between 18 and 60 years old with a percentage of 83.2%.The FAB subtype M2 occurred most frequently (27%) followed by M1 (24.8%). The cytogenetic study showed that the majority of patients had a normal karyotype. The t (8; 21) was the most detected balanced translocation in our series and the intermediate cytogenetic group was the most represented group (65.4%). A total of 461 patients (53.54%) were treated according to the protocol AML11. The Disease-free survival (DFS) was significantly better for favorable cytogenetic group as compared to other cytogenetic groups (median survival of 41.58 months for the favorable group versus 29.07 months for the adverse group; p-value = 0.02).Conclusion: The age of AML patients was younger compared to other populations. The majority of patients had a normal karyotype and the commonest balanced translocation was the t (8; 21). Survival was higher in patients with good prognosis.

Low Platelet Counts at Diagnosis Predict Better Survival for Patients with Intermediate-Risk Acute Myeloid Leukemia

2019 ◽  
Vol 143 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Yimin Zhang ◽  
Haihui Gu ◽  
Qi Chen ◽  
Ying Zhang ◽  
Hui Cheng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Negative Impact ◽  
Disease Free Survival ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Risk Patients ◽  
Immature Cells ◽  
Acute Myeloid

Background: Aggressive growth of primitive and immature cells in the bone marrow results in reductions in megakaryocyte and platelet (PLT) counts, leading to thrombocytopenia in acute myeloid leukemia (AML). However, not all AML patients show thrombocytopenia at the time of diagnosis, and the association of PLT count with patient survival is largely unknown. Methods: A retrospective study was performed to determine PLT counts at diagnosis in the peripheral blood in 291 newly diagnosed AML patients and assess the association of PLT counts with the overall survival (OS) and disease-free survival (DFS) of these patients. Results: Low PLT counts (≤40 × 109/L) were associated with better outcomes for the whole cohort (5-year OS, 55.1 ± 3.8 vs. 35.3 ± 3.5%, p < 0.001; 5-year DFS, 49.1 ± 3.8 vs. 25.7 ± 4.0%, p < 0.001) and intermediate-risk patients (5-year OS, 64.5 ± 5.4 vs. 41.0 ± 4.8%, p < 0.001; 5-year DFS, 60.8 ± 5.6 vs. 28.6 ± 5.6%, p < 0.001). Moreover, low PLT counts were related to deeper molecular remission. Low PLT counts correlated with better survival of intermediate-risk AML patients treated with chemotherapy only. Allogeneic hematopoietic stem cell transplantation attenuated the negative impact of high PLT counts on the survival of intermediate-risk patients. Furthermore, univariate and multivariate analyses demonstrated that PLT count at diagnosis was an independent prognostic factor for intermediate-risk AML. Conclusion: PLT count at diagnosis predicts survival for patients with intermediate-risk AML.

Acute myeloid leukemia and myelodysplastic syndrome in children treated for cancer: comparison with primary presentation

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 427-434 ◽  
Author(s):  
Dorothy R. Barnard ◽  
Beverley Lange ◽  
Todd A. Alonzo ◽  
Jonathan Buckley ◽  
J. Nathan Kobrinsky ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Latency Period ◽  
Disease Free Survival ◽  
Free Survival ◽  
Cell Counts ◽  
Acute Myeloid

Abstract There has not been a reported series of children with therapy-induced myelodysplastic syndrome/acute myeloid leukemia (tMDS/tAML) who were treated systematically. This paper describes 24 children with tMDS/tAML who were assigned randomly to standard- or intensive-timing induction on protocol CCG 2891. Presenting features and outcomes of those children were compared with those of 960 patients with de novo MDS (62 patients) or AML (898 patients). Children with tMDS/tAML were older at presentation (P = .015), had lower white blood cell counts (P = .01), and were more likely to have MDS (21% vs 7%) (P = .02) and trisomy 8 (P = .06). Fewer had hepatomegaly (P = .02), splenomegaly (P = .03), hepatosplenomegaly (P = .02), or classic AML translocations [t(8;21), t(15;17), 16q22; P = .02]. They had a poorer induction rate (50% vs 72%,P = .016), overall survival (26% vs 47% at 3 years,P = .007), and event-free survival (21% vs 39% at 3 years, P =.023). Disease-free survival after achieving remission was similar (45% vs 53%, P = .868). Children with tMDS/tAML who received intensive-timing induction had better outcomes than those who received standard-timing induction (overall survival 32% vs 0%, P = .54). In this study, the latency period to development of tMDS/tAML was the same for presumed alkylator-induced as for topoisomerase-induced myeloid leukemia. The findings of this study confirm that most children with tMDS/tAML have disease resistant to current therapies. Standard-timing induction appears less effective for this population.

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