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

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.

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Acute promyelocytic leukemia: Clinical and morphologic features and prognostic factors

Seminars in Hematology ◽

10.1053/shem.2001.20861 ◽

2001 ◽

Vol 38 (1) ◽

pp. 4-12 ◽

Cited By ~ 44

Author(s):

Giuseppe Avvisati ◽

Francesco Lo Coco ◽

Franco Mandelli

Keyword(s):

Prognostic Factors ◽

Acute Promyelocytic Leukemia ◽

Promyelocytic Leukemia

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Gene mutations in acute promyelocytic leukemia early death in patients treated with arsenic trioxide alone

Clinical & Translational Oncology ◽

10.1007/s12094-021-02625-6 ◽

2021 ◽

Author(s):

Xiaotong Chen ◽

Shengjin Fan ◽

Yanqiu Zhao ◽

Jin Zhou

Keyword(s):

Arsenic Trioxide ◽

Acute Promyelocytic Leukemia ◽

Gene Mutations ◽

Early Death ◽

Promyelocytic Leukemia

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Acute promyelocytic leukemia: preventing early complications and late toxicities

Hematology ◽

10.1182/asheducation-2016.1.10 ◽

2016 ◽

Vol 2016 (1) ◽

pp. 10-15 ◽

Cited By ~ 20

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.

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Progressive hyperleukocytosis is a relevant predictive marker for differentiation syndrome, early death, and subsequent relapse in acute promyelocytic leukemia

Scientific Reports ◽

10.1038/s41598-019-47937-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Jae-Ho Yoon ◽

Hee-Je Kim ◽

Gi June Min ◽

Sung-Soo Park ◽

Young-Woo Jeon ◽

...

Keyword(s):

Acute Promyelocytic Leukemia ◽

Early Death ◽

Predictive Marker ◽

Promyelocytic Leukemia ◽

Subsequent Relapse

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

Cancers ◽

10.3390/cancers11091311 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1311 ◽

Cited By ~ 6

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.

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

Haematologica ◽

10.3324/haematol.2019.230482 ◽

2019 ◽

Vol 105 (9) ◽

pp. 2286-2297 ◽

Cited By ~ 4

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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