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

2021 ◽  
Author(s):  
Xiaotong Chen ◽  
Shengjin Fan ◽  
Yanqiu Zhao ◽  
Jin Zhou
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Gene Mutations ◽  
Early Death ◽  
Promyelocytic Leukemia

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.

Causes and prognostic factors for early death in patients with acute promyelocytic leukemia treated with single-agent arsenic trioxide

2017 ◽  
Vol 96 (12) ◽  
pp. 2005-2013 ◽  
Author(s):  
Jinxiao Hou ◽  
Shuye Wang ◽  
Yingmei Zhang ◽  
Dachuan Fan ◽  
Haitao Li ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Single Agent ◽  
Early Death ◽  
Promyelocytic Leukemia

A Population Based Study of 408 Cases of Acute Promyelocytic Leukemia Showing Changes in Epidemiology and Prognosis During Two Decades: Impact of Oral Arsenic Trioxide,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3597-3597
Author(s):  
Wing-Yan Au ◽  
Dennis Ip ◽  
Oscar Mang ◽  
Kit Fai Wong ◽  
Margaret Ng ◽  
...  
Keyword(s):  
Hong Kong ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Early Death ◽  
The United States ◽  
Population Based ◽  
Promyelocytic Leukemia ◽  
Male Gender ◽  
Older Age

Abstract Abstract 3597 Background. The incidence of acute promyelocytic leukemia (APL) shows racial variations. Population based epidemiologic studies are feasible because of common diagnostic criteria and treatment. The prognosis of APL has substantially improved since the advent of all trans-retinoic acid (ATRA) and arsenic trioxide (As2O3). Material and methods. Data on survival and relapse of consecutive APL patients in Hong Kong from 1991 to 2011 were obtained from the Hong Kong Cancer Registry (with at least 98% reporting and complete follow-up), and verified by hospital records. Data were censored at the end of July 2011. Potential factors impacting on survival including age, platelet count (Plat), white blood cell count (WBC), gender; 5-year cohort and As2O3 maintenance were analyzed by logistic regression. Results. Four hundred and eight cases of APL (198 men, 210 women) at a median age of 41 (3–89) years were registered. There was a rise in cases number with successive 5-year cohorts, but the WHO standardized age incidence rate (WSIR) was unchanged (Table 1). At diagnosis (Dx), the median hemoglobin was 8.4 (2.9–14.9) g/dL, WBC 17.7 (0.3–250) × 109/L (>10 × 109/L in 129 cases) and Plat 35 (3–270) × 109/L (< 40 × 109/L in 282 cases). Early death (within 30 days of Dx) occurred in 88 cases. Complete remission (CR) was achieved in 318 cases. Outcome was unknown in 2 cases. The incidence of early death decreased progressively with each 5-year cohort (p=0.035), but was positively correlated with older age (p<0.001), high WBC (p<0.001) and male gender (trend only, p=0.06). From CR1, the median follow-up was 83 (0–249) months. Relapse occurred in 108 cases. The 5-year relapse rate fell from 54% (no maintenance) to 16% (p<0.001) with the adoption of ATRA (n=110) and oral As2O3 (n=88; since 2001) maintenance. Relapse rates were lower in patients receiving As2O3 than ATRA maintenance (17% versus 38%; p=0.008). Risk factors predicting relapse were older age (p=0.001), no oral-As2O3 maintenance (p=0.003), high WBC (p=0.023) and male gender (trend only, p=0.056). For relapsed patients, 5-year overall survival (OS) from CR1 was improved from 67% with ATRA (1993–1998) to 96% with oral-As2O3 (since 1999–2011) treatment. The causes of deaths after CR1 were APL relapse (n=35), second cancer (n=8), bone marrow transplantation (BMT, n=7), chemotherapy (n=3) and unrelated causes (n=6). Allogeneic BMT was not performed since 1999. For the last 5-year cohort (2006–2011), there were no APL related deaths after CR1. With reduction of induction death, and improvement in treatment and prevention of relapses, the 5-year OS from diagnosis increased from 44% for the first 5-year cohort to 80% for the last 5-year cohort. On multivariate analysis, age (p<0.001) and cohort period (p=0.031) were determinants of OS. Conclusions. Population based incidence data showed that APL in Hong Kong was more prevalent than the United States (0.15–0.18/100000/year). Oral-As2O3 has markedly changed the outcome of APL patients. Early death is now the greatest problem curtailing survival of APL patients. Disclosures: No relevant conflicts of interest to declare.

Long-Term Efficacy of Low-Dose All-Trans Retinoic Acid Plus Individually Adapted Chemotherapy Induction Followed by Arsenic Trioxide Based Post-Remission Therapy in Adults with Newly Diagnosed Acute Promyelocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1480-1480
Author(s):  
Yinjun Lou ◽  
Jie Jin
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Low Dose ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Abstract 1480 Acute promyelocytic leukemia (APL) is a distinct subtype of acute myelogenous leukemia (AML), which usually presents with pancytopenia, coagulopathies and bleeding. Molecular studies have revealed that it was caused by leukemogenic PML-RARA fusion gene resulting from a specific chromosomal translocation t(15;17). The administration of target agent all-trans-retinoic acid (ATRA) combined with anthracycline-based chemotherapy for induction and consolidation followed by ATRA plus low-dose chemotherapy maintenance is the standard strategies for patients with newly diagnosed APL. However, despite the high cure rate, early death and leukemia relapse are the two main important obstacles. We evaluated the efficacy of low-dose All-trans-retinoic acid (ATRA) plus individually adapted chemotherapy for induction followed by arsenic trioxide (ATO) based post-remission therapy in newly diagnosed acute promyelocytic leukemia (APL). From January 2004 to September 2011, 109 patients with APL were enrolled the study. The complete remission (CR) rate was 96.3%. The early death rate was 0.9%. Two arms were assigned according to post-remission protocols: ATO group cases were treated with standard chemotherapy, ATO, and ATRA. Without ATO group cases were subsequently treated with chemotherapy and ATRA only. Patients were monitored by reverse transcriptase-polymerase chain reaction (RT-PCR) during and after treatment. The six-year relapse-free survival (RFS) was significantly better for patients in ATO group than in without ATO group, 94.4% versus 50.6% (P < 0.0001) and the six-year overall survival (OS) rate was 95.7% versus 64.1%, in two groups (P = 0.003). This study shows that low-dose ATRA plus tailored chemotherapy is effective in induction therapy, and the addition of ATO to post-remission therapy significantly improves the long-term outcome. Disclosures: No relevant conflicts of interest to declare.

Treatment of Acute Promyelocytic Leukemia (APL) At Tawam Hospital UAE

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4347-4347
Author(s):  
Arif Alam ◽  
Harimohan Narayanan ◽  
Shanaaz Sonday ◽  
Sabir Hussain ◽  
Amar Lal ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Supportive Care ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Conflicts Of Interest ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Published Data ◽  
Female Ratio

Abstract Abstract 4347 Acute Promyelocytic Leukemia (APL) is a unique sub-type of Acute Myeloid leukemia associated with a balanced reciprocal translocation between chromosomes 15 and 17 and 80% of the cases present with bleeding diathesis caused by severe coagulopathy. The translocation generates a fusion transcript joining the PML(promyelocyte) and RAR-α (retinoic acid receptor-α) genes. The therapy of APL has been revolutionized by the introduction of differentiating agents All Trans Retinoic Acid (ATRA) and Arsenic Trioxide. All patients were treated as per Pethema protocol. Initially LPA99 (Sanz MA. Blood. 1999 Nov 1;94(9):3015-21) and since January 2012 a risk adapted therapy based on LPA2005 (Sanz MA et al. Blood June 24, 2010 vol. 115 no. 25 5137–5146). Treatment included induction followed by 3 cycles of consolidation and two years of maintenance. Nineteen patients were diagnosed with APL between January 2009 and June 2012. Three patients are excluded from the analysis as karyotyping and/or PCR did not confirm the diagnosis. The median age was 35 years (range 22–53 years). Male to female ratio was 4:1. Nine (56%) patients were stratified as high risk (WBC ≥ 10 ×109/l) while, seven (44%) as intermediate risk and low risk (WBC < 10 ×109/l). Three (19%) patients had early death despite treatment and supportive care. The cause of death was intracranial hemorrhage (1) pulmonary hemorrhage (1) and multi-organ failure (1). Thirteen patients achieved a complete morphological and molecular remission (80%). There has been only 1 case of treatment failure (high risk at presentation). This patient was successfully re-induced with arsenic trioxide and achieved second molecular complete remission. Unfortunately he relapsed a second time and is currently alive in third morphological remission but remains PCR positive for PML/RARα 33 months after diagnosis. Our limited experience shows favorable outcome (CR 80%) for the treatment of APL using the Pethema protocol compared to published data (Tallman MS. Blood 2002;99(3):759–767). Early death rate remains high despite intensive supportive care. The only variable is the availability and initiation of ATRA at the clinical suspicion of diagnosis both at the referring hospitals and treatment center. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Successful treatment of acute promyelocytic leukemia in a patient under hemodialysis with arsenic trioxide

2021 ◽  
Vol 9 (7) ◽  
Author(s):  
Akiko Hashimoto ◽  
Yasuhiro Tanaka ◽  
Takayuki Ishikawa ◽  
Isaku Shinzato
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Successful Treatment ◽  
Promyelocytic Leukemia
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