scholarly journals Immunophenotypes and Immune Markers Associated with Acute Promyelocytic Leukemia Prognosis

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Fang Xu ◽  
Chang-Xin Yin ◽  
Chun-Li Wang ◽  
Xue-Jie Jiang ◽  
Ling Jiang ◽  
...  
Keyword(s):  
Risk Factor ◽  
Acute Promyelocytic Leukemia ◽  
Independent Risk Factor ◽  
De Novo ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Immune Markers ◽  
Hla Dr ◽  
Study Population ◽  
Wbc Count

CD2+, CD34+, and CD56+ immunophenotypes are associated with poor prognoses of acute promyelocytic leukemia (APL). The present study aimed to explore the role of APL immunophenotypes and immune markers as prognostic predictors on clinical outcomes. A total of 132 patients with de novo APL were retrospectively analyzed. Immunophenotypes were determined by flow cytometry. Clinical features, complete remission (CR), relapse, and five-year overall survival (OS) rate were assessed and subjected to multivariate analyses. The CD13+CD33+HLA-DR-CD34− immunophenotype was commonly observed in patients with APL. Positive rates for other APL immune markers including cMPO, CD117, CD64, and CD9 were 68.7%, 26%, 78.4%, and 96.6%, respectively. When compared with patients with CD2− APL, patients with CD2+ APL had a significantly higher incidence of early death (50% versus 15.7%;P=0.016), lower CR rate (50% versus 91.1%;P=0.042), and lower five-year OS rate (41.7% versus 74.2%;P=0.018). White blood cell (WBC) count before treatment was found to be the only independent risk factor of early death, CR failure, and five-year mortality rate. Flow cytometric immunophenotype analysis can facilitate prompt APL diagnosis. Multivariate analysis has demonstrated that WBC count before treatment is the only known independent risk factor that predicts prognosis for APL in this study population.

scholarly journals The Impact of Flt3 Gene Mutations in Acute Promyelocytic Leukemia: A Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1311 ◽  
Author(s):  
Gledson L. Picharski ◽  
Diancarlos P. Andrade ◽  
Ana Luiza M. R. Fabro ◽  
Luana Lenzi ◽  
Fernanda S. Tonin ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Meta Analysis ◽  
Gene Mutations ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Biomedical Literature ◽  
Mixed Effect ◽  
Mixed Effect Models ◽  
Wbc Count ◽  
The Impact

The association of FLT3 mutations with white blood cell (WBC) counts at diagnosis and early death was studied in patients with acute promyelocytic leukemia (APL). Publications indexed in databases of biomedical literature were analyzed. Potential publication bias was evaluated by analyzing the standard error in funnel plots using the estimated relative risk (RR). Mixed-effect models were used to obtain the consolidated RR. All analyses were conducted using the R statistical software package. We used 24 publications in the final meta-analysis. Of 1005 males and 1376 females included in these 24 publications, 645 had FLT3-ITD (internal tandem duplication) mutations. Information on FLT3-D835 mutations was available in 10 publications for 175 patients. Concurrent occurrence of the two mutations was rare. WBC count at diagnosis was ≥10 × 109/L in 351 patients. For patients with the FLT3-ITD mutation, RR was 0.59 for overall survival (OS) and 1.62 for death during induction. For those with FLT3-D835 mutations, the RR was 0.50 for OS and 1.77 for death during induction. RR for WBC count ≥10 × 109/L was 3.29 and 1.48 for patients with FLT3-ITD and FLT3-D835, respectively. APL patients with FLT3-ITD or FLT3-D835 are more likely to present with elevated WBC counts and poorer prognosis than those without these mutations.

An effective early death scoring system for predicting early death risk in de novo acute promyelocytic leukemia

2020 ◽  
Vol 61 (8) ◽  
pp. 1989-1995 ◽  
Author(s):  
Ping Cai ◽  
Qian Wu ◽  
Yemin Wang ◽  
Xiaofei Yang ◽  
Xinyou Zhang ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Scoring System ◽  
De Novo ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Death Risk

Difference in causes and prognostic factors of early death between cohorts with de novo and relapsed acute promyelocytic leukemia

2017 ◽  
Vol 97 (3) ◽  
pp. 409-416 ◽  
Author(s):  
Hongli Zhao ◽  
Yanqiu Zhao ◽  
Yingmei Zhang ◽  
Jinxiao Hou ◽  
Huiyuan Yang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Acute Promyelocytic Leukemia ◽  
De Novo ◽  
Early Death ◽  
Promyelocytic Leukemia

scholarly journals Status of Early Mortality in Newly Diagnosed Cases of Acute Promyelocytic Leukaemia (APL) in BSMMU Hospital

1970 ◽  
Vol 18 (2) ◽  
pp. 150-154
Author(s):  
F Rahman ◽  
ABM Yunus ◽  
AL Kabir ◽  
M Begum ◽  
A Aziz ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Acute Promyelocytic Leukaemia ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Promyelocytic Leukaemia ◽  
Laboratory Evaluation ◽  
Total Study Population ◽  
Term Survival ◽  
Study Population

Background: Acute promyelocytic leukemia (APL), is now curable in most cases with current treatment strategies. But limited available data suggest that the rate of early mortality is high and long term survival is poor in many developing countries. To improve the survival rate by reducing early mortality, study of the status of early mortality as the main cause of treatment failure for the management of APL as a heamatological emergency appears to have a great significance. Materials and method: Diagnosis of acute promyelocytic leukemia was done from bone marrow morphological study by experienced haematologist. After that cytogenetic study to see chromosomal translocation 15 and 17 and molecular study to see PML-RARá fusion protein was also done. Clinical and laboratory evaluation was done to all of them. Chemotherapy according to IC-APL protocol was given to 30 out of 40 patients. Incidence of early mortality (death within 14 days of diagnosis) was recorded and also categorized according to cause of death. Pattern of supportive cares given to the patients such as management of coagulopathy. ATRA syndrome or sepsis to treat the disease as a medical emergency was also recorded. Result: Selected clinical, laboratory and outcome data of 40 cases of APL who were admitted in Haematology department of BSMMU was surveyed. The median age overall was 32 yrs. The median WBC count at diagnosis was 7.75×109/L and median platelet count 25×109/L. Laboratory evidence of DIC was noted in 37.5% of patients. Death occurred within 14 days of diagnosis (early death) in 10 (25%) cases. Bleeding was the most common cause of early death, then infectious complication and ATRA syndrome. Among 30 patients who got chemotherapy complete remission (CR) was 66.6%. So only 50% of the total study population was able to achieve CR. So due to early mortality, a significant portion of the study population could not receive protocol based treatment. Conclusion: To improve outcome by reducing initial mortality early recognition and treatment of APL is required in specialized institutions, by prompt and aggressive supportive therapy as well as immediate starting of antileukemic agent such as ATRA, arsenic trioxide etc.  Key words: Acute Promyelocytic Leukaemia (APL); mortality. DOI: 10.3329/jdmc.v18i2.6277 J Dhaka Med Coll. 2009; 18(2) : 150-154

scholarly journals Developing a Simple Algorithm Based on Multiparameter Flow Cytometry for Fast Screening of Acute Promyelocytic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Vitória Ceni Ceni ◽  
Katia B Pagnano ◽  
Gislaine B O Duarte ◽  
Marina DB Pellegrini ◽  
Bruno Kosa Duarte ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Discriminant Analysis ◽  
Acute Promyelocytic Leukemia ◽  
Simple Algorithm ◽  
Diagnostic Algorithm ◽  
Promyelocytic Leukemia ◽  
Advisory Board ◽  
Multiparameter Flow Cytometry ◽  
Fast Screening ◽  
Hla Dr

Introduction: Acute promyelocytic leukemia (APL) is a genetically and molecularly well-defined type of acute leukemia that is curable but has a frequent early mortality due to bleeding. So, there is a need for a fast diagnostic screening in order to start appropriate therapy. Multiparameter flow cytometry (MFC) is usually performed in all types of acute myeloid leukemias (AMLs) but only few features have been described as characteristic of APL. Aim: to develop a diagnostic algorithm based on the intensity of expression of several antigens examined by MFC in AML that could reliably discriminate between APL and the other types of AML. Material and Methods: Consecutive newly diagnosed AMLs treated in our Institution during the last 2 years entered the study. Immunophenotyping was included in the diagnostic workup. An 8-color platform based on the Euroflow recommendations was used. The mean fluorescence intensity (MFI) of each antigen tested was assessed and those best discriminating between APL and all other types of AML were obtained by a discriminant analysis. Phenotypic characteristics of normal myeloblasts taken from examinations of bone marrow (BM) MFC performed for the diagnosis of cytopenias were used as controls. Results: 24 cases of APL and 56 cases of other primary AML entered the study. Median age: 39 (23-56) and 62(26-81) years respectively. Concerning ELN risk groups of non-APL cases, 13 were favorable risk, 26 were intermediate and 09 were adverse risk. In 8 cases risk assessment was not possible due to the absence of cytogenetics. Moreover, among APL patients, 7 cases had a FLT3-ITD mutation. Among non-APL AMLs, 4 had FLT3-ITD mutation, 4 had NPM1 and 10 had FLT3-ITD and NPM1mutation. Concerning antigen expression, CD34 was expressed in only 1/24 APL samples, and in 18/56 samples from non-APL AMLs. The following flow features were differentially expressed in both groups: SSC (p <0.0001), CD45 (p=0.02), CD13 (p=0.001), CD64 (p=0.004), HLA-DR (p<0.0001) and CD33 (p<0.0001) (Table 1). In the discriminant analysis, MFI CD34 and MFI HLA-DR were able to accurately classify APL and non-APL AML in only 62.5%. However, after the addition of the ratio of SSC between blasts and lymphocytes, these 3 parameters were able to differentiate APL from non-APL AML in 91.2% of the cases. Conclusion: MFC was adequate for a fast screening of APL in most cases. Expression of CD34 was not very useful, as many AMLs do not express this antigen, similar to APL, but SSC, together with HLA-DR could discriminate both types of leukemia in most cases. Disclosures Pagnano: Astellas: Other: Advisory Board and lecture; Novartis: Other: Advisory Board; Pintpharma: Other: Lecture; EMS: Other: Lecture. Duarte:Janssen: Other: Lecture; Astellas: Other: Lecture.

scholarly journals Acute promyelocytic leukemia: preventing early complications and late toxicities

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Sameem Abedin ◽  
Jessica K. Altman
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Promyelocytic Leukemia ◽  
Myeloid Leukemia ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Early Complications ◽  
Younger Patients ◽  
Success Stories ◽  
Acute Myeloid

Abstract Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which presents with a distinct coagulopathy. Therapeutic advances have made APL one of the true success stories in oncology, transforming this once lethal disease into the most curable form of AML. For many patients, cure will now be achieved without the use of chemotherapy. It is hoped that limiting chemotherapy will reduce mortality even further, particularly among more vulnerable older adults whose survival lagged behind that of younger patients. It should be noted that early death persists in patients with APL and continues to negatively affect survival. Further, among survivors treated with chemotherapy or even arsenic trioxide (ATO), there remains the potential for long-term toxicities that must be monitored. Understanding the management of these issues is an important complement to ensure maximal survival for patients with APL.

scholarly journals ASLAN003, a potent dihydroorotate dehydrogenase inhibitor for differentiation of acute myeloid leukemia

Haematologica ◽  
2019 ◽  
Vol 105 (9) ◽  
pp. 2286-2297 ◽  
Author(s):  
Jianbiao Zhou ◽  
Jessie Yiying Quah ◽  
Yvonne Ng ◽  
Jing-Yuan Chooi ◽  
Sabrina Hui-Min Toh ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Promyelocytic Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Leukemia Cell ◽  
Promyelocytic Leukemia ◽  
Dihydroorotate Dehydrogenase ◽  
Isocitrate Dehydrogenase 1 ◽  
Pyrimidine Synthesis ◽  
Acute Myeloid

Differentiation therapies achieve remarkable success in acute promyelocytic leukemia, a subtype of acute myeloid leukemia. However, excluding acute promyelocytic leukemia, clinical benefits of differentiation therapies are negligible in acute myeloid leukemia except for mutant isocitrate dehydrogenase 1/2. Dihydroorotate dehydrogenase catalyses the fourth step of the de novo pyrimidine synthesis pathway. ASLAN003 is a highly potent dihydroorotate dehydrogenase inhibitor that induces differentiation, as well as reduces cell proliferation and viability, of acute myeloid leukemia cell lines and primary acute myeloid leukemia blasts including in chemo-resistant cells. Apoptotic pathways are triggered by ASLAN003, and it also significantly inhibits protein synthesis and activates AP-1 transcription, contributing to its differentiation promoting capacity. Finally, ASLAN003 substantially reduces leukemic burden and prolongs survival in acute myeloid leukemia xenograft mice and acute myeloid leukemia patient-derived xenograft models. Notably, the drug has no evident effect on normal hematopoietic cells and exhibits excellent safety profiles in mice, even after a prolonged period of administration. Our results, therefore, suggest that ASLAN003 is an agent targeting dihydroorotate dehydrogenase with potential in the treatment of acute myeloid leukemia. ASLAN003 is currently being evaluated in phase 2a clinical trial in acute myeloid leukemia patients.

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