Prognostic factors of patients with newly diagnosed acute Promyelocytic Leukemia treated with Arsenic Tridoxide-based frontline therapy
تعیین فاکتورهای پروگنوستیک با توجه به یافته های فلوسیتومتری، سیتوژنتیک و مولکولی در بیماران مبتلا به لوسمی پرومیلوسیتیک حاد درمان شده با رژیم های حاوی آرسنیک تری اکسید
[Dissertation]
Amirhossein Mirhosseini
امیر حسین میر حسینی
Tehran University of Medical Sciences, Medicine school
1400
68p
Doctor of Philosophy (phd)
Adult hematology and oncology
2022/03/13 - 1400/12/22
Subject: Prognostic factors of patients with newly diagnosed acute Promyelocytic Leukemia treated with Arsenic Tridoxide-based frontline therapyBackground: Conventional karyotyping on banded metaphases has shown that, in addition to the specific t(15;17), 30% to 35% of acute promyelocytic leukemia(APL) patients have additional cytogenetic abnormalities(ACA), most frequently trisomy 8.Material & Methods: In this retrospective cohort study the patients with de novo APL who referred to Sharati Hospital since 2001, were enrolled. The diagnosis of APL was genetically confirmed in all cases by demonstration of the PML/RARα hybrid gene and/or the chromosomal translocation t(15;17)(q22;q21). For all patients, initial symptoms (hemorrhagic or thrombotic event), CBC, renal function tests, FDP, D-Dimer, Fibrinogen level, flow cytometry, PML RARa and cytogenetic study were recorded. A total of 200 patients (97 female and 103 male) with newly diagnosed APL received single-agent arsenic trioxide and 220 patients (118 female and 102 male) with newly diagnosed APL received ATRA plus ATO with or without chemotherapy.Results: This study shows that roughly 30% of patients with APL have ACA besides the t(15;17) that trisomy 8 is by far the most frequent abnormality, accounting for about 30% of the additional abnormalities. In the context of state-of-the-art treatment with on ATO based therapy, the presence of ACA, associated with leukocytosis and CD34 positive at flow cytometry. No significant relationship was seen between the presence of ACAs and OS/DFS, Moreover, reduced OS and DFS were found in patients with abnl(17p). Our study showed that the expression rate of CD2 was 27.1%, FLT3 mutation 31%, CD34 expression 20.4% and early mortality 9.1%. The patients with CD2 & CD34 expression presented with higher initial WBC count, coagulopathy and showed increased early mortality. The early mortality, OS and DFS showed obvious differences compared with CD2 & CD34 negative patients. Nevertheless, no significant relationship between OS, DFS and expression of CD2 & CD34 marker in the group of patients who survived after 30 days were seen. The patients who presented the FLT3-ITD mutation revealed no significant difference in OS as compared to the patients without mutation. Moreover, significant relations were seen between the presence of FLT3 mutation and leukocytosis, coagulopathy, APL differentiation syndrome and early mortality. Our study revealed early mortality rate was 9.1% and had meaningful correlation with: Age (more than 50 years), leukocytosis, Coagulopathy, Expression of CD2 & CD34.Conclusion: The lack of independent prognostic value of additional chromosomal abnormalities, FLT3 mutation and CD2, CD34 expression in acute promyelocytic leukemia does not support the use of alternative therapeutic strategies when such abnormalities are found.
acute promyelocytic leukemia
additional cytogenetic abnormalities
FLT3 mutation
CD2
CD34 expression
, Author
, Author
Mirhosseini, Amirhossein
میر حسینی، امیر حسینی
, Thesis advisor
, Thesis advisor
, Thesis advisor
, Thesis advisor
, Consulting advisor
, Consulting advisor
, Consulting advisor
, Consulting advisor
Mousavi, Asadollah
موسوی، اسداله
Yaghmaee, Marjan
یغمایی، مرجان
Kasaeian, Amir
کساییان، امیر
Chardevali, Bahram
چهاردولی، بهرام
Tehran University of Medical Sciences, Medicine school