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.

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 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 Effective Treatment of Acute Promyelocytic Leukemia With All-Trans-Retinoic Acid, Arsenic Trioxide, and Gemtuzumab Ozogamicin

2009 ◽  
Vol 27 (4) ◽  
pp. 504-510 ◽  
Author(s):  
Farhad Ravandi ◽  
Eli Estey ◽  
Dan Jones ◽  
Stefan Faderl ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Promyelocytic Leukemia ◽  
Platelet Recovery ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Purpose We examined the outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) with or without gemtuzumab ozogamicin (GO) but without traditional cytotoxic chemotherapy. Patients and Methods From February 2002 to March 2008, 82 patients with APL were treated with a combination of ATRA plus ATO. The first cohort of 65 patients received ATRA and ATO (beginning on day 10 of ATRA). High-risk patients (WBCs ≥ 10 × 109/L) received GO on the first day. From July 2007, the second cohort of 17 patients received ATRA and ATO concomitantly on day 1. They also received GO on day 1, if high risk, and if their WBC increased to more than 30 × 109/L during induction. Monitoring for PML-RARA fusion gene was conducted after induction and throughout consolidation and follow-up. Results Overall, 74 patients achieved complete remission (CR) and one achieved CR without full platelet recovery after the induction, for a response rate of 92%. Seven patients died at a median of 4 days (range, 1 to 24 days) after inclusion in the study from disease-related complications. The median follow-up is 99 weeks (range, 2 to 282 weeks). Among the responding patients, three experienced relapse at 39, 52, and 53 weeks. Three patients died after being in CR for 14, 21, and 71 weeks, all from a second malignancy. The estimated 3-year survival rate is 85%. Conclusion The combination of ATRA and ATO (with or without GO) as initial therapy for APL was effective and safe and can substitute chemotherapy-containing regimens.

Salvage Therapy with Chemotherapy- or Arsenic Trioxide-Based Regimens for Acute Promyelocytic Leukemia in First Relapse.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1062-1062
Author(s):  
Pau Montesinos ◽  
Jordi Esteve ◽  
Edo Vellenga ◽  
Concha Rivas ◽  
Salut Brunet ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Arsenic Trioxide ◽  
Salvage Therapy ◽  
Promyelocytic Leukemia ◽  
Second Line ◽  
Front Line ◽  
Second Line Therapy ◽  
Early Relapse ◽  
Line Therapy

Abstract Abstract 1062 Poster Board I-84 Background: Arsenic trioxide (ATO) is currently regarded as the best treatment option in relapsed acute promyelocytic leukemia (APL). The efficacy and safety of salvage therapy using an ATO-based approach compared with chemotherapy-based regimens is not well established. We analyze the clinical outcome of 110 APL patients relapsing after front-line therapy with ATRA and anthracycline, who received second-line therapy with chemotherapy- or ATO-based regimens. Methods: From June 1997 to May 2009, 110 patients (69 M/41 F; median age: 40 years, 2-81) relapsed after front-line therapy with PETHEMA trials (LPA96, n=30, LPA99, n=60; and LPA2005, n=20). Patients presented with either molecular relapse (n=37) or hematological relapse (n=73, 14 of them involving central nervous system). Sixty-seven patients (61%) followed salvage therapy with chemotherapy-based regimens. Therapy consisted of induction with mitoxantrone plus cytarabine plus ATRA (n=46), EMA (n=7), or other chemotherapy regimens (n=14). Thirty-four patients (51%) received one consolidation cycle followed by stem-cell transplantation (SCT) (autologous, 20; allogeneic, 14). Patients not eligible for SCT received consolidation therapy with or without maintenance therapy. From October 2003, 43 patients (49%) received salvage therapy with ATO-based regimens, comprising induction with ATO (0.15 mg/kg intravenously until CR) followed by one consolidation cycle with ATO plus ATRA. Twenty-three patients (53%) received intensification therapy with SCT (autologous, 19; allogeneic, 4). Patients not eligible for SCT received maintenance therapy with ATO plus ATRA with or without Mylotarg or other chemotherapy. Results: Baseline characteristics, including age at relapse, were similar in both cohorts of patients, but patients treated with ATO-based regimens were more frequently late relapses (>18 months after initial APL diagnosis) (67% vs. 40%, P=0.005). The median follow-up in the chemotherapy-based group was 62 months (range, 6-134), and 18 months (range, 2-53) in the ATO-based group. CR rates were 84% in the chemotherapy-based group (8 deaths and 3 resistances) and 88% in the ATO-based group (3 deaths and 2 resistances) (P=0.48). Molecular remission was achieved after consolidation in 79% and 91%, respectively (P=0.13). Twenty-two patients of the chemotherapy-based group that achieved CR were not transplanted because of ineligibility for SCT (n=4), early relapse before planned SCT (n=7), mobilization failure (n=4), clinical decision/toxicity (n=6), and short follow-up (n=1). Reasons for not SCT in the ATO-based group were ineligibility for SCT (n=6), early relapse before planned SCT (n=5), and short follow-up (n=4). The 2-year overall survival (OS), disease-free (DFS), and relapse-free survival (RFS) in the chemotherapy-based group and in the ATO-based group were 44% vs. 63% (P=0.05), 34% vs. 33% (P=0.51), and 37% vs. 34% (P=0.61), respectively. For patients not receiving SCT, the 2-year OS, DFS, and RFS in the chemotherapy-based group and in the ATO-based group were 38% vs. 26% (P=0.98), 34% vs. 23% (P=0.57), and 37% vs. 23% (P=0.46), respectively. For patients receiving autologous SCT, the 2-year OS, DFS, and RFS in the chemotherapy-based group and in the ATO-based group were 60% vs. 87% (P=0.03), 40% vs. 38% (P=0.38), and 42% vs. 41% (P=0.37), respectively. For patients receiving allogeneic SCT, the 2-year OS, DFS, and RFS in the chemotherapy-based group and in the ATO-based group were 56% vs. 100% (P=0.15), 26% vs. 37% (P=0.46), and 28% vs. 37% (P=0.53), respectively. Conclusions: this study performed in a large series of APL patients relapsing after upfront therapy with ATRA and anthracycline shows high rates of CR either with ATO (88%) or chemotherapy regimens (84%). The 2-year DFS and RFS were similar in patients who received second-line therapy with chemotherapy- or ATO-based regimens. However, an apparent benefit in terms of OS was observed in the ATO-based group (P=0.05), suggesting a potential role in minimizing toxicity after administering ATO as salvage therapy. Disclosures: No relevant conflicts of interest to declare.

Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia

2021 ◽  
pp. 107815522110247
Author(s):  
Kyle Zacholski ◽  
Bryan Hambley ◽  
Erin Hickey ◽  
Sarah Kashanian ◽  
Andrew Li ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
All Trans Retinoic Acid ◽  
Grade 3 ◽  
Disease Free

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination therapy yields high complete remission and disease-free survival rates in acute promyelocytic leukemia (APL). ATO is dosed on actual body weight and high ATO doses in overweight patients may contribute to increased toxicity. We performed a retrospective, two-center study comparing toxicities in patients who received the Lo-Coco et al ATRA/ATO regimen with capped ATO, ≤10 mg/dose, and non-capped ATO, >10 mg/dose. A total of 44 patients were included; 15 received doses ≤10 mg and 29 received >10 mg. During induction, there was no difference in the incidence of grade ≥3 hepatotoxicity, grade ≥3 QTc prolongation, neurotoxicity, and cardiac toxicity between groups. In consolidation, patients receiving >10 mg/dose experienced a greater incidence of neurotoxicity (66.7% vs 22.2%; p = 0.046). Capping doses saved $24634.37/patient and reduced waste of partially-used vials. At a median follow-up of 27 months, no disease relapses occurred in either group. This represents an opportunity to improve the safety profile of this highly effective regimen.

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

scholarly journals Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial)

2021 ◽  
Vol 118 (6) ◽  
pp. e2020382118
Author(s):  
Li Chen ◽  
Hong-Ming Zhu ◽  
Yan Li ◽  
Qi-Fa Liu ◽  
Yu Hu ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Link Type ◽  
Kaplan Meier ◽  
Risk Patients ◽  
The Difference ◽  
Grade 3

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

scholarly journals Oral arsenic trioxide–based maintenance regimens for first complete remission of acute promyelocytic leukemia: a 10-year follow-up study

Blood ◽  
2011 ◽  
Vol 118 (25) ◽  
pp. 6535-6543 ◽  
Author(s):  
Wing-Yan Au ◽  
Cyrus R. Kumana ◽  
Harold K. K. Lee ◽  
Shek-Ying Lin ◽  
Herman Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Chemotherapeutic Agents ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
Wbc Count ◽  
First Complete Remission

Abstract Seventy-six patients with acute promyelocytic leukemia (APL) in first complete remission after induction and consolidation by daunorubicin and cytosine arabinoside received oral arsenic trioxide (As2O3)-based maintenance. Three regimens were used: oral As2O3 (10 mg/day, regimen A, n = 20), oral As2O3 plus all-trans retinoic acid (ATRA, 45 mg/m2 per day, regimen AA, n = 19), and oral As2O3 plus ATRA plus ascorbic acid (1000 mg/day, regimen AAA, n = 37), each given for 2 weeks every 2 months for 2 years. Patients receiving A, AA, and AAA maintenance did not differ significantly in clinicopathologic features and risk factors. Headache, dyspepsia, reversible liver function derangement, and herpes zoster reactivation were adverse effects observed during maintenance. QTc prolongation and arrhythmias were not encountered. At a median follow-up of 24 months (range, 1-115 months), there were 8 relapses. The 3-year leukemia-free-survival, event-free-survival, and overall-survival were 87.7%, 83.7%, and 90.6%, respectively. Adverse prognostic factors included male gender for leukemia-free-survival, and unrelated cancers for overall survival. Age, presentation WBC count and platelet count, and the type of oral As2O3 maintenance regimens had no impact on survivals. Prolonged oral As2O3 maintenance was feasible and safe and resulted in favorable outcomes when used with a simple induction and consolidation regimen compared with other protocols composed of multiple chemotherapeutic agents.

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