scholarly journals Importance of monitoring arsenic methylation metabolism in acute promyelocytic leukemia patients receiving the treatment of arsenic trioxide

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Yu Zheng ◽  
Yuan-Fei Mao ◽  
Hui-Jin Zhao ◽  
Li Chen ◽  
Li-Ning Wang ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Arsenic Speciation ◽  
Promyelocytic Leukemia ◽  
Chronic Liver ◽  
Dimethylarsinic Acid ◽  
Metabolic Pattern ◽  
Methylation Index ◽  
Arsenic Methylation

Abstract Background Arsenic trioxide [ATO, inorganic arsenite (iAsIII) in solution] plays an important role in the treatment of acute promyelocytic leukemia (APL). However, the long-term adverse effects (AEs) and the retention of arsenic among APL patients are rarely reported. In this study, we focused on arsenic methylation metabolism and its relationship with chronic hepatic toxicity, as we previously reported, among APL patients who had finished the treatment of ATO. Methods A total of 112 de novo APL patients who had completed the ATO-containing treatment were enrolled in the study. Arsenic species [iAsIII, inorganic arsenate (iAsV), and their organic metabolites, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] in patients’ plasma, urine, hair and nails were detected by high-performance liquid chromatography combined with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Eighteen single nucleotide polymorphisms (SNPs) of the arsenic (+ 3 oxidative state) methylation transferase (AS3MT) gene, which was known as the main catalyzer for arsenic methylation, were tested with the polymerase chain reaction method. Results The study showed the metabolic pattern of arsenic in APL patients undergoing and after the treatment of ATO, in terms of total arsenic (TAs) and four species of arsenic. TAs decreased to normal after 6 months since cessation of ATO. But the arsenic speciation demonstrated significantly higher portion of iAsIII in patient’s urine (40.08% vs. 1.94%, P < 0.001), hair (29.25% vs. 13.29%, P = 0.002) and nails (30.21% vs. 13.64%, P = 0.003) than the healthy controls’, indicating a decreased capacity of arsenic methylation metabolism after the treatment of ATO. Urine primary methylation index (PMI) was significantly lower in patients with both chronic liver dysfunction (0.14 vs. 0.28, P = 0.047) and hepatic steatosis (0.19 vs. 0.3, P = 0.027), suggesting that insufficient methylation of arsenic might be related to chronic liver disorders. Two SNPs (A9749G and A27215G) of the AS3MT gene were associated with impaired urine secondary methylation index (SMI). Conclusions The long-term follow-up of arsenic speciation indicated a decreased arsenic methylation metabolism and a probable relationship with chronic hepatic disorders among APL patients after the cessation of ATO. Urine PMI could be a monitoring index for chronic AEs of ATO, and the SNPs of AS3MT gene should be considered when determining the dosage of ATO.

Maintenance therapy with arsenic after induction in an alternative and long-term case for the prevention of recurrence of acute promyelocytic leukemia during the period between November 2005 and December 2011.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6556-6556
Author(s):  
Mozaffar Aznab ◽  
Ghobad Salimi ◽  
Jafar Navabi ◽  
Touraj Jouybari ◽  
Mansour Rezaei ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Term Therapy ◽  
First Line ◽  
First Line Therapy

6556 Background: Arsenic trioxide has been used in the first line treatment of acute promyelocytic leukemia and also for recurrence after ATRA and chemotherapy. In this study, it we used it in induction of remission and maintenance therapy Methods: Between November 2005 to December 2011, 42 patients admitted in our department with APL diagnosis. There were 27 male and 15 women with a median age of 28 years. Arsenic trioxide started at 0.15 mg/kg intravenous infusion till patient’s bone marrows achieve to complete remission. Then, after 28 days rest, we did consolidation with Arsenic trioxide with the same dosage for 28 more days. We continued treatment with 14 days courses of Arsenic trioxide every 3-4 months for 2 years, as maintenance therapy Results: Four patients died during the first 20 days of treatment. Thirty-eight patients achieved to remission. Two patients refused to continue treatment after achieving to remission and excluded from this study. Thirty-six patients finished whole treatment. After a median follow-up of 54 months, 4 patients died due to disease relapse and one patient relapsed and initiated treatment with Arsenic and ATRA. Five patients faced leukocytosis over 100,000/ml. In these cases we were obligated to discontinue Arsenic for 3-4 days and did chemotherapy by Danourobicin for 2 days. Totally 8 patients died during remission induction and long-term follow up. One year, 3 and 5 years RFS were 97%, 87.1% and 79.4 respectively and we didn’t observe any relapse for patients who remained in remission after 5 years. Finally, 31 patients are alive and free of disease. The overall survival was 79.5% for our cohort. Conclusions: Arsenic trioxide is an effective treatment as the first line therapy for new cases of APL and long term therapy with will reduce the risk of diseases recurrence without any major toxicity in long time.

Arsenic speciation in hair and nails of acute promyelocytic leukemia (APL) patients undergoing arsenic trioxide treatment

Talanta ◽  
2018 ◽  
Vol 184 ◽  
pp. 446-451 ◽  
Author(s):  
Baowei Chen ◽  
Fenglin Cao ◽  
Xiufen Lu ◽  
Shengwen Shen ◽  
Jin Zhou ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Arsenic Speciation ◽  
Promyelocytic Leukemia

Single-Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Long-Term Follow-Up Data

2010 ◽  
Vol 28 (24) ◽  
pp. 3866-3871 ◽  
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Ezhilarasi Chendamarai ◽  
Kavitha M. Lakshmi ◽  
Salamun Desire ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Risk Group ◽  
Single Agent ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Long Term Follow Up

Purpose We previously reported our results with a single-agent arsenic trioxide (ATO) –based regimen in newly diagnosed cases of acute promyelocytic leukemia (APL). The concern remained about the long-term outcome of this well-tolerated regimen. We report our long-term follow-up data on the same cohort. Patients and Methods From January 1998 to December 2004, 72 patients with PML/RARα+ APL were enrolled. All patients were treated with a single-agent ATO regimen. Results Overall 62 (86.1%) achieved a hematologic remission (complete remission). After the initial report, an additional seven patients have relapsed for a total of 13 relapses. There were no additional toxicities to report on follow-up. At a median follow-up 60 months, the 5-year Kaplan-Meier estimate (± SE) of event-free survival, disease-free survival, and overall survival (OS) was 69% ± 5.5%, 80% ± 5.2%, and 74.2% ± 5.2%, respectively. The OS in the good risk group as defined by us remains 100% over this period. Conclusion Single-agent ATO as used in this study in the management of newly diagnosed cases of APL is safe and is associated with durable responses. Results in the low-risk group are comparable to that reported with conventional therapy while additional interventions would probably be required in high-risk cases.

scholarly journals Very long term follow-up data of pediatric acute promyelocytic leukemia treated with upfront arsenic-trioxide based regimens

2018 ◽  
Vol 3 (3) ◽  
pp. S29
Author(s):  
Fouzia NA ◽  
AnuKorula AnupDevasia ◽  
Uday Kulkarnim Yasir Jeelani ◽  
Thenmozhi Mani JeyaseelanLakshmanan ◽  
Alok Srivastava ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Long Term Follow Up

scholarly journals Very Long Term Follow-up Data of Pediatric Acute Promyelocytic Leukemia Treated with Upfront Arsenic-Trioxide Based Regimens

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1400-1400 ◽  
Author(s):  
Fouzia N. ◽  
Anu Korula ◽  
Anup Joseph Devasia ◽  
Uday Prakash Kulkarni ◽  
Yasir Jeelani Samoon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retrospective Analysis ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Pediatric Patients ◽  
Pediatric Population ◽  
Promyelocytic Leukemia ◽  
Long Term Follow Up

Abstract Combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) is currently considered the standard of care in the management of acute promyelocytic leukemia (APL). While APL is considered a highly curable malignancy there is recognition that the outcome in pediatric patients is inferior to that reported in young adults. There have been concerns raised in the past on the potential long term side effects of the use of ATO, especially in a pediatric population. There is limited long term follow up data on the use of ATO in the pediatric population. At our center we have been using ATO based regimens to treat pediatric and adult patients with APL since 1998 and hence we undertook this retrospective analysis to evaluate the long term clinical outcomes and toxicity profile in the pediatric cohort. Data on all consecutive pediatric patients (age ≤18yrs) diagnosed with APL and treated in the Department of Haematology, Christian Medical College, Vellore, from January, 1998 to December, 2017 were included in this retrospective analysis. Of the total 73 patients with age ≤ 18yrs diagnosed during this period, 5 refused treatment and were discharged against medical advice. Treatment in the remaining 68 patients consisted of single agent ATO until 2015 (n=57), as reported previously by us (Mathews et al. Blood 2016). From 2015 combination of ATO, ATRA ± an anthracycline in induction and consolidation was administered in a risk adjusted manner (n=11). The median age was 2 years (range: 2-18) with equal gender distribution (50% each). Sixty two (91.2%) achieved complete hematologic remission (CR), 5 (7.4%) early deaths occurred from intracranial hemorrhage (n=3), neutropenic sepsis (n=1) and pulmonary thrombo-embolism (n=1), one patient did not achieve CR at the end of induction. The median time to CR was 45 days (range: 25- 62). Other acute ATO-related toxicities were low grade, transient and not associated with any mortality (transaminitis = 12 [17.6%]; ATRA like syndrome = 6 [8.8%]). With a median follow-up of 71 months, the 5 year OS and EFS of pediatric cohort (n=68) was 78.9±5.2% and 61.8±6.4% respectively (Fig 1). Among the 62 patients in CR, 21 (33.9%) relapsed at a median of 18 months (range: 5-126) from the initial diagnosis; 16 bone marrow, 3 bone marrow+CNS and 2 molecular relapses; an additional 2 patients died in remission (one viral encephalitis and another data not available). Nineteen out of 21 (90.5%) patients who relapsed received ATO based re-induction while 2 refused treatment and were discharged at request. Out of the 19 treated patients, all attained second CR. CR was consolidated with an autologous SCT (n=10) or ATO based chemotherapy (n=9). The OS and EFS of the 19 relapsed patients was 72.9±10.4% and 68±10.8% respectively. On long term follow up of this pediatric cohort (median follow up 71 months; 18 (26.5%) > 10 years follow up and 37 (54.5%) > 5 years follow up) there were no long term renal, hepatic, metabolic complications or second malignancies noted. Our results indicate the high efficacy and long term safety of ATO based regimens in the treatment of children with APL. Even among the relapse pediatric APL patients treated with upfront ATO, salvage chemotherapy with ATO based regimen followed by autologous stem cell transplantation is associated with excellent long term survival and is not associated with any major long term complications. Disclosures No relevant conflicts of interest to declare.

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