Pretreatment platelet count predicts survival outcome of patients with de novo non-M3 acute myeloid leukemia

Background Pretreatment platelet count has been reported as a potential tool to predict survival outcome in several solid tumors. However, the predictive value of pretreatment platelet count remains obscure in de novo acute myeloid leukemia (AML) excluding acute promyelocytic leukemia (M3). Methods We conducted a retrospective review of 209 patients with de novo non-M3 AML in our institute over a period of 8 years (2007–2015). Receiver operating characteristic (ROC) curve analysis was used to determine the optimal platelet (PLT) cutoff in patients. We analyzed the overall survival (OS) and disease free survival (DFS) using the log-rank test and Cox regression analysis. Results By defining the platelet count 50 × 109/L and 120 × 109/L as two cut-off points, we categorized the patients into three groups: low (<50 × 109/L), medium (50–120 × 109/L) and high (>120 × 109/L). On univariate analysis, patients with medium platelet count had longer OS and DFS than those with low or high platelet count. However, the multivariate analysis showed that only longer DFS was observed in patients with medium platelet count than those with low or high platelet count. Conclusion Our findings indicate that pretreatment platelet count has a predictive value for the prognosis of patients with non-M3 AML.

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

Blood ◽

10.1182/blood.v120.21.2544.2544 ◽

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.

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Prognostic Implication of Therapy-Related Acute Myeloid Leukemia after Comparative Analysis with De Novo acute Myeloid Leukemia

Blood ◽

10.1182/blood.v126.23.4884.4884 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4884-4884

Author(s):

Jae-Ho Yoon ◽

Byung-Sik Cho ◽

Hee-Je Kim ◽

Seung-Ah Yahng ◽

Seung-Hwan Shin ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Induction Chemotherapy ◽

Myeloid Leukemia ◽

De Novo ◽

Chromosomal Abnormalities ◽

Survival Outcome ◽

Poor Survival ◽

Poor Survival Outcome ◽

De Novo Aml ◽

Acute Myeloid

Abstract Background: Therapy-related acute myeloid leukemia (t-AML) is regarded as a complication after cytotoxic chemotherapy and/or radiation therapy, and also considered to have a poor survival outcome compared to de novo AML. We still have a question whether t-AML itself indicates a poor prognosis or whether the inferior outcome results from the association with such an adverse characteristics including cytogenetic risk or age or underlying malignancies. Methods: In this single center retrospective study, 1825 patients (median 46 years old [range, 17-92]) with variable karyotypes were enrolled from 2002 to 2013. Fifty-four (3.0%) patients had previous malignancies or autoimmune diseases, and all of them were treated with radiation or toxic chemotherapy before diagnosis of t-AML with a median duration of 36.3 months (range, 2.9-280.5). We analyzed clinical outcomes compared to 1771 de novo AML patients who were not related with any toxic therapies before. Results: Among 54 t-AML patients, 42 (77.8%) was in remission of prior malignant disease and 8 were in stable disease and 4 were in relapsed disease. In t-AML subgroup, median age was older (50 vs. 46 years old, p =0.119), leukocyte and bone marrow blast counts were significantly lower than de novo AML subgroup. There were more female patients in t-AML subgroup (70.3% vs. 45.4%, p=0.003). Among 38 female t-AML patients, 13 (34.2%) patients had breast cancer, 10 patients had hematological malignancies (i.e. APL in 5, lymphoma in 3, multiple myeloma in 2), and 8 (21.1%) had gynecological malignancies (i.e. ovarian and cervical cancer etc.). One or more chromosomal abnormalities (82.6% vs. 68.3%, p=0.015) and more adverse-risk karyotypes (41.2% vs. 20.0%, p<.001) were in t-AML subgroup. Especially, t-AML had more 5 or 7 chromosomal abnormalities (7.8% vs. 2.0%, p=.004) and complex karyotypes (27.5% vs. 7.6%, p<.001) which also included abnormal 5 or 7 chromosomes. Smaller number of t-AML patients received induction chemotherapy (74.1% vs. 87.6%, p=0.006) and early death rate was higher in t-AML group (22.2% vs. 13.7%, p=.083). After median follow-up of 70 months (range: 5.6-165.0), t-AML showed inferior 5-year overall survival (OS) compared to de novo AML (23.8% vs. 39.0%, p <.001). The result was more significant in intermediate to poor-risk group (9.2% vs. 30.0%, p<.001), but it was similar in favorable-risk group (75.0% VS. 62.8%, p=.532). In treated cohort, however, remission rate (70.0% vs. 79.3%, p =.149) and relapse rate (28.8% vs. 35.9%, p =.544) was not different, and multivariate analysis showed t-AML did not affect OS (HR=1.25, p=.185), while age >50 years old (HR=1.48, p<.001), hematopoietic cell transplantation (HCT, HR=0.37, p<.001), favorable-risk karyotype (HR=0.48, p<.001), and post-induction remission status (HR=0.26, p<.001) did. Five-year OS of t-AML patients treated with HCT (n=16) was 50.0%, and for intermediate to poor-risk subgroup treated with HCT, 5-year OS was 33.3%. Conclusion: In this study, t-AML was related with a larger proportion of adverse-risk karyotype, and many patients could not start induction chemotherapy due to old age, and remained prior malignant disease, which might result in poor survival outcome. On the other hand, response to induction chemotherapy of t-AML was similar with de novo AML consistent with a recent report (Kayser et al. Blood 2011). Therefore, if previous malignancy is in remission or in stable disease, aggressive treatment strategy using HCT may overcome poor survival outcome of t-AML. Disclosures No relevant conflicts of interest to declare.

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Bmi-1 Expression Is Useful To Design Therapy and To Predict Prognosis in Patients with Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v106.11.3296.3296 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3296-3296

Author(s):

Moniruddin Chowdhury ◽

Keichiro Mihara ◽

Nanae Nakaju ◽

Sachiko Fukumoto-Hidani ◽

Yoshihiro Takihara ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Standard Dose ◽

Intensive Therapy ◽

Univariate Analysis ◽

Granulocytic Sarcoma ◽

High Dose ◽

Binary Logistic Regression Model ◽

Acute Myeloid

Abstract Since prognosis of patients with acute myeloid leukemia (AML) is highly variable even in a single subpopulation in FAB classification, it would be useful to find prognostic molecular markers for AML. Thus, we investigated Bmi-1 expression in AML cells by flow cytometry and analyzed whether it predicts prognosis in AML patients and further it is helpful to choose therapies in the modalities of treatment options, because it is known to be required for self-renewal mechanism of leukemic stem cells. Bmi-1 expression in bone marrow or peripheral blood cells was analyzed in 49 patients with AML (M0(n=5), M1(n=7), M2(n=6), M3(n=5), M4(n=8), M5(n=5), M6(n=1)), granulocytic sarcoma(n=1), MDS-AML (n=9), and secondary AML(n=2). Freshly isolated AML cells were stained with a PE-conjugated anti-CD34-antibody followed by fixation and then with anti-Bmi-1-antibody-FITC. All of patients with low Bmi-1 positivity (<35%, n=11) except for de novo AML(M0) entered in complete remission (CR) with single induction chemotherapy(n=5) and accordingly had better overall survival, even though lower dose of chemotherapy (60% of standard dose) was given (n=3). Alternatively, patients with higher percentage of Bmi-1 expression in AML cells (> 70%, n=19) except for AML(M3) progressed to death within two years, unless they were treated with highly intensive therapy such as high dose AraC or allogeneic stem cell transplantation (n=3). Patients with intermediate degree of Bmi-1 expression (35–60%, n=5) responded to standard intensity of chemotherapy (n=2) and are alive for more than two years. Interestingly, patients with MDS-AML (n=9) had high Bmi-1 expression (79%) and all of them have died within 20 months. Binary logistic regression model showed that significant correlation was found among survival status as dependent variable, Bmi-1, and treatment intensity as independent variable (p = 0.004). On the other hand, Univariate analysis did not reveal any relation of Bmi-1 expression to karyotype, age, WBC count, or FAB subtype. In conclusion, Bmi-1 expression could be an independent prognostic marker and useful tool to design therapy for the AML patients.

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Rebound Thrombocytosis following Induction Chemotherapy Is an Independent Predictor of a Good Prognosis in Acute Myeloid Leukemia Patients Attaining First Complete Remission

Acta Haematologica ◽

10.1159/000369917 ◽

2015 ◽

Vol 134 (1) ◽

pp. 32-37 ◽

Cited By ~ 6

Author(s):

Umit Yavuz Malkan ◽

Gursel Gunes ◽

Ayse Isik ◽

Eylem Eliacik ◽

Sezgin Etgul ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Recovery Time ◽

Cox Regression ◽

De Novo ◽

Statistical Significance ◽

Good Prognosis ◽

Platelet Recovery ◽

Cox Regression Analysis ◽

Acute Myeloid

There are very few data about the relationship between acute myeloid leukemia (AML) prognosis and bone marrow recovery kinetics following chemotherapy. In this study, we aimed to assess the prognostic importance and clinical associations of neutrophil and platelet recovery rates and rebound thrombocytosis (RT) or neutrophilia (RN) in the postchemotherapy period for newly diagnosed AML patients. De novo AML patients diagnosed between October 2002 and December 2013 were evaluated retrospectively. One hundred patients were suitable for inclusion. Cox regression analysis using need for reinduction chemotherapy as a stratification parameter revealed RT as the only parameter predictive of OS, with borderline statistical significance (p = 0.06, OR = 7; 95% CI 0.92-53), and it was the only parameter predictive of DFS (p = 0.024, OR = 10; 95% CI 1.3-75). In order to understand whether RT or RN was related to a better marrow capacity or late consolidation, we considered neutrophil recovery time and platelet recovery time and nadir-first consolidation durations in all patients in the cohort. Both the marrow recovery duration and the time between marrow aplasia and first consolidation were shorter in RT and RN patients. To our knowledge, this is the first study to report a correlation between RT/RN and prognosis in AML.

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Effect of initial absolute monocyte count on survival outcome of patients with de novo non-M3 acute myeloid leukemia

Leukemia & Lymphoma ◽

10.3109/10428194.2016.1166491 ◽

2016 ◽

Vol 57 (11) ◽

pp. 2548-2554 ◽

Cited By ~ 5

Author(s):

Jianhua Feng ◽

Wei Zhang ◽

Junqing Wu ◽

Shenmeng Gao ◽

Haige Ye ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Survival Outcome ◽

Monocyte Count ◽

Acute Myeloid

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Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia

Blood ◽

10.1182/blood.v83.6.1603.bloodjournal8361603 ◽

1994 ◽

Vol 83 (6) ◽

pp. 1603-1611 ◽

Cited By ~ 127

Author(s):

A Neubauer ◽

RK Dodge ◽

SL George ◽

FR Davey ◽

RT Silver ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Univariate Analysis ◽

Bone Marrow Blast ◽

Ras Mutations ◽

Ras Genes ◽

Oligonucleotide Hybridization ◽

Acute Myeloid

Mutations of the N- and K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis. Despite these observations, little is known about the clinical importance of ras mutations in AML. We studied the clinical impact of ras mutations in 99 patients with de novo AML. All patients were treated in two prospective multicenter trials. The polymerase chain reaction was used to amplify areas surrounding the codons 12, 13, and 61 of the three ras genes N-, K-, and H-ras from DNA from bone marrow cells, ras mutations were detected by an algorithm based on allele-specific oligonucleotide hybridization. Eighteen of 99 (18%) patients harbored mutations in either N- or K-ras. All of the observed mutations occurred in N-ras (N = 10) and K-ras (N = 5) or concurrently in both N- and K-ras (N = 3). There were no significant differences between ras-negative and ras- positive patients according to age, sex, blood counts, cytogenetic abnormalities, or French-American-British classification. However, univariate analysis suggested a longer survival in ras-positive patients (P = .11). When adjusted for age, which was the most important factor affecting outcome, the presence of a ras mutation emerged as a significant predictor for improved survival (P = .03) and along with lower bone marrow blast counts (P = .02) and better cytogenetic category (P = .01). However, the presence of an aberrant ras allele was strongly correlated with lower bone marrow blast counts (P = .007). Thus, whether a mutation in the N-ras or K-ras proto-oncogenes directly affects treatment outcome or indirectly through an association with lower leukemic burden remains to be determined. Nevertheless, these findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies.

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Relevance of immunophenotypes to prognostic subgroups of age, WBC, platelet count, and cytogenetics in de novo acute myeloid leukemia

Apmis ◽

10.1111/j.1600-0463.2010.02694.x ◽

2010 ◽

Vol 119 (1) ◽

pp. 76-84 ◽

Cited By ~ 12

Author(s):

XIAOQING LI ◽

JUAN LI ◽

WEN DU ◽

JIAHUA ZHANG ◽

WEI LIU ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Platelet Count ◽

Myeloid Leukemia ◽

De Novo ◽

Acute Myeloid

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The role of neuronal apoptosis inhibitory protein (NAIP) in acute myeloid leukemia patients

Acta Haematologica Polonica ◽

10.2478/ahp-2019-0011 ◽

2019 ◽

Vol 50 (2) ◽

pp. 74-80

Author(s):

Agnieszka Pluta ◽

Tadeusz Robak ◽

Kamil Brzozowski ◽

Barbara Cebula-Obrzut ◽

Agata Majchrzak ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Neuronal Apoptosis ◽

De Novo ◽

Univariate Analysis ◽

Malignant Neoplasm ◽

Inhibitory Protein ◽

Response To Chemotherapy ◽

Neuronal Apoptosis Inhibitory Protein ◽

Acute Myeloid

AbstractAcute myeloid leukemia (AML) is a heterogeneous, highly malignant neoplasm. Apoptosis is a complex process executed by caspases and suppressed by the inhibitor of apoptosis (IAP) family. Neuronal apoptosis inhibitory protein (NAIP), IAP’s member, may play an exceptional role in the mechanisms of tumors’ resistance to chemotherapy. The aims of the study were to assess the expression of NAIP in leukemic blasts of AML patients using flow cytometry and to evaluate its influence on disease outcome. NAIP expression was found in 106 out of 108 patients. A higher complete response rate was associated with a low expression of NAIP, age < 60 yo, and white blood cell count < 20 G/L (p = 0.009, p = 0.033, and p = 0.076, respectively) in univariate analyses and a low NAIP expression and age < 60 yo (p = 0.025 and p = 0.013, respectively) in multivariate analyses. Longer overall survival (OS) in the univariate analysis was influenced by a low NAIP expression, age < 60 yo, and intensive chemotherapy (p = 0.033, p < 0.001, and p < 0.001, respectively). In the intensively treated group, better OS was observed in patients with age < 60 yo, de novo AML, and a low NAIP expression (p = 0.03, p = 0.024, and p = 0.07, respectively). In multivariate analysis, longer OS was associated with age < 60 yo (p = 0.009) and de novo AML (p = 0.007). In conclusion, we suggest that NAIP might play an adverse role in response to chemotherapy.

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Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia

Blood ◽

10.1182/blood.v83.6.1603.1603 ◽

1994 ◽

Vol 83 (6) ◽

pp. 1603-1611 ◽

Cited By ~ 13

Author(s):

A Neubauer ◽

RK Dodge ◽

SL George ◽

FR Davey ◽

RT Silver ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Univariate Analysis ◽

Bone Marrow Blast ◽

Ras Mutations ◽

Ras Genes ◽

Oligonucleotide Hybridization ◽

Acute Myeloid

Abstract Mutations of the N- and K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis. Despite these observations, little is known about the clinical importance of ras mutations in AML. We studied the clinical impact of ras mutations in 99 patients with de novo AML. All patients were treated in two prospective multicenter trials. The polymerase chain reaction was used to amplify areas surrounding the codons 12, 13, and 61 of the three ras genes N-, K-, and H-ras from DNA from bone marrow cells, ras mutations were detected by an algorithm based on allele-specific oligonucleotide hybridization. Eighteen of 99 (18%) patients harbored mutations in either N- or K-ras. All of the observed mutations occurred in N-ras (N = 10) and K-ras (N = 5) or concurrently in both N- and K-ras (N = 3). There were no significant differences between ras-negative and ras- positive patients according to age, sex, blood counts, cytogenetic abnormalities, or French-American-British classification. However, univariate analysis suggested a longer survival in ras-positive patients (P = .11). When adjusted for age, which was the most important factor affecting outcome, the presence of a ras mutation emerged as a significant predictor for improved survival (P = .03) and along with lower bone marrow blast counts (P = .02) and better cytogenetic category (P = .01). However, the presence of an aberrant ras allele was strongly correlated with lower bone marrow blast counts (P = .007). Thus, whether a mutation in the N-ras or K-ras proto-oncogenes directly affects treatment outcome or indirectly through an association with lower leukemic burden remains to be determined. Nevertheless, these findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies.

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High EVI1 Expression Predicts Adverse Outcomes in Children With De Novo Acute Myeloid Leukemia

Frontiers in Oncology ◽

10.3389/fonc.2021.712747 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yongzhi Zheng ◽

Yan Huang ◽

Shaohua Le ◽

Hao Zheng ◽

Xueling Hua ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Regression Analysis ◽

Myeloid Leukemia ◽

Pediatric Patients ◽

Cox Regression ◽

De Novo ◽

Adverse Outcomes ◽

Cox Regression Analysis ◽

Pediatric Aml ◽

Acute Myeloid

BackgroundA high ecotropic viral integration site 1 (EVI1) expression (EVI1high) is an independent prognostic factor in adult acute myeloid leukemia (AML). However, little is known of the prognostic value of EVI1high in pediatric AML. This study aimed to examine the biological and prognostic significance of EVI1high in uniformly treated pediatric patients with AML from a large cohort of seven centers in China.MethodsA diagnostic assay was developed to determine the relative EVI1 expression using a single real-time quantitative polymerase chain reaction in 421 newly diagnosed pediatric AML patients younger than 14 years from seven centers in southern China. All patients were treated with a uniform protocol, but only 383 patients were evaluated for their treatment response. The survival data were included in the subsequent analysis (n = 35 for EVI1high, n = 348 for EVI1low).ResultsEVI1high was found in 9.0% of all 421 pediatric patients with de novo AML. EVI1high was predominantly found in acute megakaryoblastic leukemia (FAB M7), MLL rearrangements, and unfavorable cytogenetic aberrance, whereas it was mutually exclusive with t (8; 21), inv (16)/t (16; 16), CEBPA, NPM1, or C-KIT mutations. In the univariate Cox regression analysis, EVI1high had a significantly adverse 5-year event-free survival (EFS) and overall survival (OS) [hazard ratio (HR) = 1.821 and 2.401, p = 0.036 and 0.005, respectively]. In the multivariate Cox regression analysis, EVI1high was an independent prognostic factor for the OS (HR = 2.447, p = 0.015) but not EFS (HR = 1.556, p = 0.174). Furthermore, EVI1high was an independent adverse predictor of the OS and EFS of patients with MLL rearrangements (univariate analysis: HR = 9.921 and 7.253, both p < 0.001; multivariate analysis: HR = 7.186 and 7.315, p = 0.005 and 0.001, respectively). Hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) provided EVI1high patients with a tendential survival benefit when compared with chemotherapy as a consolidation (5-year EFS: 68.4% vs. 50.8%, p = 0.26; 5-year OS: 65.9% vs. 54.8%, p = 0.45).ConclusionIt could be concluded that EVI1high can be detected in approximately 10% of pediatric AML cases. It is predominantly present in unfavorable cytogenetic subtypes and predicts adverse outcomes. Whether pediatric patients with EVI1high AML can benefit from HSCT in CR1 needs to be researched further.

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