Improved long-term survival in all Sanz risk patients of newly diagnosed acute promyelocytic leukemia treated with a combination of retinoic acid and arsenic trioxide-based front-line therapy

2018 ◽  
Vol 36 (3) ◽  
pp. 584-590 ◽  
Author(s):  
Yinjun Lou ◽  
Ying Lu ◽  
Zhijuan Zhu ◽  
Yafang Ma ◽  
Shanshan Suo ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Front Line ◽  
Term Survival ◽  
Line Therapy ◽  
Risk Patients

Quantitative analysis of PML-RARα in newly diagnosed acute promyelocytic leukemia patients treated with arsenic trioxide as a front-line therapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6571-6571
Author(s):  
S. H. Ghaffari ◽  
S. Rostami ◽  
D. Bashash ◽  
K. Alimoghaddam ◽  
A. Ghavamzadeh
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Transcript Level ◽  
Threshold Level ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Rt Pcr ◽  
Front Line ◽  
Line Therapy

6571 Background: Recently, patients with acute promyelocytic leukemia (APL) have experienced significant clinical gains after treatment with arsenic trioxide (As2O3). However, the potential role for use of this agent as a front-line therapy for newly diagnosed patients is unclear. Methods: From 95 patients with APL, 85 patients who achieved complete remission (CR) were sequentially evaluated during 4–60 months period of follow-up by conventional RT-PCR. A total of 30 patients (6 relapsed and 24 in continued long remission) were selected and monitored by quantitative real-time PCR (RQ-PCR) assay. Using ‘Hybridization Probes‘ technology, the expression of PML-RARα/G6PDH transcript ratio was analyzed in serial PB samples taken at different courses of disease and the results were compared with the clinical outcome. Results: More than 90% of patients obtained molecular remission, as determined by conventional RT-PCR in 1–3 months after start of arsenic therapy. RQ-PCR analyses showed a rapid rate of clearance of PML-RARα/G6PDH transcript level during the courses of arsenic therapy. In majority of the patients in CR the level of PML-RARα/ G6PDH ratio was always below 5×102 in PB samples. In all the relapsed cases with follow-up intervals of 1–6 months (median 3) clinical relapse was predictable by increasing transcript level above this threshold. Conclusions: Using a sensitive and quantitative method provided valuable information about effectiveness of arsenic as a front-line therapy in the management of newly diagnosed APL. Our study highlights the usefulness of PB and the definition of threshold level for early prediction of relapse. The threshold level correlates well with relapse risk; therefore, transcript ratio below the level should be regarded as a goal in the clinical management of this disease. No significant financial relationships to disclose.

Front-Line Therapy with Arsenic Trioxide/All-Trans-Retinoic Acid Combination and Chemotherapy Improves Cure Rates in Newly Diagnosed Patients with Acute Promyelocytic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2970-2970
Author(s):  
Jiong Hu ◽  
Yuan-fang Liu ◽  
Chuan-feng Wu ◽  
Guang-biao Zhou ◽  
Zhi-Xiang Shen ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Healthy Donors

Abstract BACKGROUND: In this study, we analyzed the clinical benefit and safety of upfront use of all-trans-retinoic acid (ATRA), arsenic trioxide (ATO) and chemotherapy in patients with newly-diagnosed acute promyelocytic leukemia (APL) during Apr 2001 and Dec 2005. METHODS: A total of 85 patients were treated with ATRA and ATO as induction therapy, followed by consolidation/maintenance therapy composed of ATRA, ATO and chemotherapy. All patients were followed-up to evaluate the long-term efficacy and safety. RESULTS: A total of 81 (95.3%) patients entered complete remission (CR) with a median of 27 days. Among these 81 patients, 4 patients relapsed and 2 patients died from the disease with a median follow-up of 70 months (15–87). The 5-year leukemia-free survival (5-yr-LFS) and overall survival (5-yr-OS) for all patients were 89.2±3.4% and 91.7±3.0% while for patients who achieved CR (n=81), the 5-yr-LFS and 5-yr-OS were 96.2±2.1% and 96.2±2.1% respectively. With careful monitoring of in vivo arsenic levels in 33 evaluable long-term survivors, we demonstrated that the serum and urine arsenic concentrations were within safety limits, although a slight but significantly increase in arsenic levels was observed as compared to healthy donors. Overall, no obvious arsenic associated long-term toxicity was documented in these patients. CONCLUSIONS: Use of up-front ATRA/ATO/chemotherapy combination treatment in newly-diagnosed APL has proven relatively safe and has lead to a significant improvement in long-term LFS/OS.

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.

scholarly journals Arsenic Trioxide As a Front-Line Therapy for Newly Diagnosed Acute Promyelocytic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4937-4937
Author(s):  
Weihong Chen ◽  
Xin Du ◽  
Jiacai Zhuo
Keyword(s):  
Complete Remission ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Fusion Gene ◽  
Promyelocytic Leukemia ◽  
The Other ◽  
Refractory Disease ◽  
Newly Diagnosed ◽  
Front Line ◽  
Line Therapy

Abstract PURPOSE: Arsenic trioxide (ATO) is a very effective drug for acute promyelocytic leukemia (APL). However, little has been reported concerning its use as front-line therapy for complete remission of newly diagnosed APL with t(15;17) chromosomal abnormality. METHODS: The adult patients newly diagnosed with APL with t(15;17) chromosomal abnormality (which would invariably lead to a positive PML/RAR alpha fusion gene) were received 4-5 weeks of ATO administered intravenous drip at a daily dose of 10mg(concentration 2%)/day as induced chemotherapy. When a complete remission was achieved by the ATO induction, a three weeks interval would be observed, after which 5 + 3 days of maintenance (with cytarabine and anthracycline, respectively) would be carried out. A further interval of 2 weeks would then take place, after which all-trans retinoic (ATRA) would be administered oral for another 2 weeks. A final interval of 2 weeks after the administration of ATRA would take place before a recurrence of the chemotherapy regimen, which would restart again with ATO induction. After PML/RAR alpha fusion gene Q-PCR tested negative, the regimen would continue recurring, ensuring negativity of the gene for 2 years. After 2 years the regimen would end, and PML/RAR alpha fusion gene of the patients were to be observed/monitored once every 3-6 months for 10 years. Central nervous system leukemia (CNSL), which might be caused by APL, was to be prevented by lumbar punctures chemotherapy once every 6-8 weeks after complete remission of the patients. Six times were taken. RESULTS: Out of 496 for newly diagnosed APL from 2005 to 2015, we identified 113 patients as newly diagnosed APL. All patients achieved complete response after treatment with ATO induced chemotherapy. Sixty-two out of 65 (95.38%) patients with APL were cured with ATO induction and subsequent 5 + 3 maintenance (cytarabine and anthracycline) therapy from 2005 to 2010. The other three patients were relapsed or had refractory disease and then died. Forty-six out of 48 patients (95.83%) achieved complete cytogenetic remission from 2011 to 2015. The other two patients were relapsed or had refractory disease and then died. All patients had no serious adverse events. Five patients had dyspnea, fever, weight gain, peripheral edema and were successfully treated with dexamethason and furosemide. CONCLUSIONS: Arsenic trioxide is a very effective drug as the front-line therapy for newly diagnosed acute promyelocytic leukemia. Disclosures No relevant conflicts of interest to declare.

scholarly journals Real Life Experience with ATRA-Arsenic Trioxide Based Regimen in Acute Promyelocytic Leukemia - Updated Results of the Prospective German Intergroup Napoleon Registry

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2815-2815
Author(s):  
Uwe Platzbecker ◽  
Eva Lengfelder ◽  
Katharina S Goetze ◽  
Christoph Röllig ◽  
Michael Kramer ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Research Funding ◽  
Real Life ◽  
Study Groups ◽  
Promyelocytic Leukemia ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
Front Line ◽  
Line Therapy

Abstract Background: Standard therapy of acute promyelocytic leukemia has long relied on the combination of All-trans-retinoic acid (ATRA) and chemotherapy. The introduction of arsenic trioxide (ATO) in APL treatment has allowed achievement of similarly high remission and survival rates coupled with significantly reduced myelosuppression. Recent results of the APL0406 trial by the GIMEMA-AMLSG-SAL study groups showed that the combination of ATRA and arsenic trioxide (ATO) is superior to standard ATRA and chemotherapy (CHT) in front-line therapy of low/intermediate risk acute promyelocytic leukemia (APL). The implications of these results for the clinical practice of APL patients in Germany have been uncertain given the fact that ATO is not formally licensed for front-line therapy of APL. Aim:In order to provide evidence and a reflection of the clinical reality of APL patient care in Germany an intergroup APL registry (National acute promyelocytic leukemia (APL) observational study, NAPOLEON) was recently initiated by several AML study groups. Methods:Eligible patients are adults at least 18 years of age with newly diagnosed or relapsed APL not beyond the first year of diagnosis. Here we report the first analysis on the series of patients prospectively enrolled into this registry. The study was conducted in accordance with the Declaration of Helsinki, received IRB approval by all participating centers and was registered at ClinicalTrials.gov (NCT02192619). Results: As of August 1st 2016, 88 patients have been included into the study with a median age of 57 years (range 22-87). All had newly diagnosed APL (100%) with 66% (n=58) being of low/intermediate risk according to the Sanz score. Out of those patients 76% (n=44) received an ATO-ATRA based induction regimen followed by a median of 4 courses of consolidation (according to the APL 0406 study).Of 41 patients evaluable for response to induction, 40/41 (98%) patients achieved complete remission (CR) with the ATRA-ATO arms. Early death rate within 30 days of therapy was 2% (1/44). After a median follow-up of 12 months, the event-free survival, cumulative incidence of relapse and overall survival at 12 months for these patients were 97%, 0% and 97%, respectively. Therapy was well tolerated and no new safety signals have been obtained. Conclusion:These real life data from a prospective German registry provide further evidence for the safety and sustained anti-leukemic efficacy of ATRA-ATO in low/intermediate risk APL. These results further support ATRA-ATO as the new standard of care in this clinical setting. Table Demographic, clinical and laboratory characteristics of the eligible patients. Table. Demographic, clinical and laboratory characteristics of the eligible patients. Disclosures Platzbecker: TEVA: Honoraria, Research Funding. Greiner:BMS: Research Funding. Thiede:AgenDix: Employment, Other: Ownership. Hochhaus:BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding.

scholarly journals Remission in Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide (varitrinox) As the First Line in Colombia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Gustavo Milone ◽  
Samuel Sarmiento Doncel ◽  
Carol Agudelo Rico ◽  
Fabiola Vizcarra Reyes ◽  
Gina Alejandra Diaz Mosquera ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Conflicts Of Interest ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
First Line ◽  
Risk Patients

Acute promyelocytic leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) in which a chromosomal translocation t (15; 17) (q22; q12) is generated by fusing produces a hybrid PML / RARα gene, generating an altered signal . The combination of transretinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of newly diagnosed standard risk patients with acute promyelocytic leukemia (APL) in several countries. The objective of the present study is to describe the frequency of remission in patients with acute promyelocytic leukemia who were administered as a first line Arsenic Trioxide (varitrinox) during the period from November 2017 to June 2020 in Colombian patients. Methods: Retrospective observational and descriptive study of 12 patients diagnosed with acute promyelocytic leukemia treated with ATO Arsenic trioxide (Varitrinox) as first line, the source of information was provided by the treating hematologists (medical records) by filling out the technical concept format. Active pharmacovigilance scientist in Colombia, this format keeps the identification information of the patient anonymized and the confidentiality of the data is guaranteed as well as compliance with the rules of good clinical practice. Results: Twelve patients with age range between 22 and 69 years with a median age of 34.0 were analyzed. It was found in the analysis that 100% had induction hematologic remission with a median of 45 days. 75% of patients received ATO + ATRA and were at low and intermediate risk, the remaining 25% received ATRA + ATO + Chemotherapy and were at high risk, and intermediate risk. 91.7% of molecular remission in consolidation was obtained and it was measured in cycle 3 by means of PCR (undetectable), 8.3% (n = 1) was positive 3% and is finishing consolidation. Regarding the most frequent adverse events, intravascular coagulation (n = 9), neutropenia (n = 6) and thrombocytopenia (n = 6) were observed. 75% of patients are disease-free, 16.7% are on maintenance (they received ATO + ATRA + Induction chemotherapy) and 8.3% are on consolidation. So far, none of the patients under study have died. Conclusions: Our results support the use of ATO (Varitrinox) in newly diagnosed APL patients (as first line), as a care strategy for low, intermediate and high risk patients. The role of ATRA-ATO is guaranteed in other studies where they manage patients of different risks. Key words: Arsenic trioxide, leukemia promyelocytic acute, leukemia myeloid acute, remission induction, tretinoin. Disclosures No relevant conflicts of interest to declare.

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