scholarly journals Successes in the Evolution of Front-Line Therapy in Pediatric Acute Promyelocytic Leukemia

2021 ◽  
Vol 4 (3) ◽  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Front Line ◽  
Line Therapy

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.

scholarly journals Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance ofFLT3mutations and complex karyotype

2014 ◽  
Vol 55 (7) ◽  
pp. 1523-1532 ◽  
Author(s):  
Xavier Poiré ◽  
Barry K. Moser ◽  
Robert E. Gallagher ◽  
Kristina Laumann ◽  
Clara D. Bloomfield ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Prognostic Significance ◽  
Promyelocytic Leukemia ◽  
Complex Karyotype ◽  
Front Line ◽  
Line Therapy

Treatment of Acute Promyelocytic Leukemia

Hematology ◽  
2006 ◽  
Vol 2006 (1) ◽  
pp. 147-155 ◽  
Author(s):  
Miguel A. Sanz
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Residual Disease ◽  
Promyelocytic Leukemia ◽  
Controversial Issues ◽  
Front Line ◽  
Hematopoietic Stem ◽  
Line Therapy ◽  
All Trans Retinoic Acid ◽  
Life Threatening ◽  
Unfit Patients

Abstract Cure of acute promyelocytic leukemia (APL) is now a possibility for most patients through the use of state-of-the-art treatments, which include simultaneous administration of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy for induction and consolidation, as well as ATRA-based maintenance. Risk-adapted strategies to modulate treatment intensity may be an effective approach to minimize therapy-related morbidity and mortality while maintaining the potential of cure. In this context, there is no role for hematopoietic stem cell transplantation (HSCT) in front-line therapy, except for the small fraction of patients with persistent minimal residual disease at the end of consolidation. However, HSCT plays an important role for patients in second complete remission. In contrast, an increasing role of arsenic trioxide (ATO) is emerging. Given the high antileukemic efficacy observed with ATO in patients relapsing after ATRA-containing regimens, this agent is currently regarded as the best treatment option in this setting. However, until a randomized comparison between the standard therapy and ATO-based regimens in front-line therapy is available, this latter approach should only be recommended for unfit patients for whom chemotherapy is contraindicated. In addition to reviewing current consensus and controversial issues on antileukemic strategies, this review addresses other aspects that can be crucial for the outcome of individual patients. These aspects include supportive care, recognition and treatment of life-threatening complications, evaluation of response, and, finally, management of the disease in special conditions such as older patients, children and pregnant women.

scholarly journals Oral Arsenic Trioxide in Front Line Therapy for Acute Promyelocytic Leukemia. A Prospective Costa Rican Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3838-3838 ◽  
Author(s):  
Mariela Rodriguez ◽  
Ronald Rojas ◽  
Alejandra Vargas ◽  
Miguel Angel Rodriguez ◽  
Claudia Garcia ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Oral Formulation ◽  
Promyelocytic Leukemia ◽  
Front Line ◽  
Line Therapy ◽  
Grade 3

KEY WORDS: Acute Promyelocytic Leukemia, oral Arsenic Trioxide, ATRA, Front Line Therapy. CONTEXT: Studies showed the combination of all-trans-retinoic acid (ATRA) with Arsenic trioxide (ATO) as an effective treatment of patients with newly diagnosed Acute Promyelocytic Leukemia (APL), permitting a chemotherapy-free treatment approach. Oral formulations of ATO were developed with similar efficacy compared to the IV formulation, and a slightly safer profile. OBJECTIVE:To determine the effectiveness and safety of a locally produced oral ATO with ATRA as a first line therapy in APL. DESIGN:We designed the LPCR05 protocol based on established treatment protocols. Treatment regimen: Induction phase: all patients received ATRA (45 mg/m2 daily) and an locally produced oral formulation of ATO (10 mg daily), with a dose of Idarubicin (12 mg/m2 on days 1,3,5 and 7, if older than 60 years only given on day 1) added only to the high-risk patients. Consolidation Phase: 3 cycles of ATO + ATRA for 30days every 6 weeks. Maintenance Phase: 4 Cycles of ATRA+ATO daily for 15 days every 3 months. Oral formulation for ATO is prepared by the Laboratory of Pharmaceutical Products from our Social Security System according to the literature and approved by local health and pharmaceutical regulators. RESULTS: We report data on our first 26 APL patients enrolled on the LPCR05 protocol. Six patients were classified as high risk, eighteen intermediate and two low risk (Table 1). One high risk patient discontinued after first consolidation because of lost follow up. The median follow up is 12.5 months. Hematological complete remission was obtained after 30 days of treatment in all 26 patients. Molecular complete remission in 22 evaluated patients after first and third consolidation was achieved in 95% and 100% respectively (Table 2). None of the patients have relapsed. There were no withdrawals of the protocol because of side effects and no induction deaths because of coagulopathy. No severe cardiac or neurological toxicity was found. Grade 3 hepatic toxicity was seen in two patients, in both cases, temporary discontinuation of ATRA and ATO resolved the side effect. One patient developed non treatment related grade 3 renal toxicity and other one developed a probably related grade 3 skin toxicity. Severe infectious complications were seen in three patients, two had pneumoniae (one death) and one enteritis (Table 3). Patients are managed in the ambulatory setting, with fewer hospitalizations (mean hospitalization days per patient of 38,1 with ATRA + chemotherapy vs 14,1 with oral ATO and ATRA), and therefore the cost is three times lower (US$65 208 vs US$24 195) than our previous approach with ATRA + chemotherapy protocol. CONCLUSION: Our data demonstrate both efficacy and safety of oral ATO with ATRA as front line therapy in all risk groups. This strategy also demonstrated lower operational costs, fewer hospitalization days, and improved convenience for patients. We expect longer follow-up will confirm that treatment with oral ATO and ATRA is a curative therapeutic strategy for patients with APL that is particularly attractive for use in low and medium income countries. 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.

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