The authors report the experience of The M. D. Anderson Cancer Center with As2O3 in the treatment of patients with recurrent APL. Epub 2014 May 8. : Twenty patients with newly diagnosed APL were treated with As2O3 (0.16 mg/kg per day) and ATRA (45 mg/m2 per day) until they achieved a CR. At the time of morphologic CR, 7 of 10 patients who were evaluated by PCR analysis (70% of patients; 95% confidence interval; 0.35–0.93) achieved a molecular remission. 2014 Jul;132:156-67. doi: 10.1016/j.envres.2014.03.012. Oxidation number (also called oxidation state) is a measure of the degree of oxidation of an atom in a substance (see: Rules for assigning oxidation numbers). Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma. trans reported 8 of 11 tested patients in molecular CR after two courses of therapy. As2S3: (arsenic oxidation state) Let oxidation no of arsenic be x. There is little information on the frequency of molecular remissions with ATRA alone, because this agent is used most frequently in combination with chemotherapy during induction. All 12 patients achieved CR. The data showed that the energy separation (eV) between As2O5 and As2S3 was 5.8, between As2O3 and As2O5 was 3.6, and between As2S3 and As2O3 was 2.1. Journal of Vascular and Interventional Radiology. Arsenic Trioxide and Acute Promyelocytic Leukemia: Clinical and Biological. Arsenic(III) oxide react with sodium hydroxide to produce sodium orthoarsenite and water. AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility. Still, is important that patients who are treated with As2O3 are monitored closely for cardiac and electrolyte abnormalities. Role of Arsenic Trioxide in Acute Promyelocytic Leukemia. 2010 Jul 13;18(1):88-98. doi: 10.1016/j.ccr.2010.06.003. Sodium hydroxide - concentrated solution. Upon recurrence, he received ATRA without response, achieved a remission after treatment with idarubicin plus cytarabine, and was consolidated with 1 cycle of the same regimen, developing recurrent disease after 56 weeks. Although As2O3 is known to regulate activation of several signaling cascades, the key events, accounting for its antileukemic properties, remain to be defined. De Loma J, Skröder H, Raqib R, Vahter M, Broberg K. Toxicol Appl Pharmacol. This glassy, white, deliquescent solid is relatively unstable, consistent with the rarity of the As(V) oxidation state. As a medication it is used to treat a type of cancer known as acute promyelocytic leukemia. 0 0. coby. 2018 Oct 15;357:80-87. doi: 10.1016/j.taap.2018.08.020. 2). American Journal of Health-System Pharmacy. The median patient age at the time of treatment with As2O3 was 44 years (range, 24–72 years). Impurities: Na 2 HAsO 3. EKGs were required weekly, and bone marrow aspirates were repeated to assess response. Sigma-Aldrich offers abstracts and full-text articles by [Yasen Maimaitiyiming, Chao Wang, Shi Xu, Khairul Islam, Ye Jia Chen, Chang Yang, Qian Qian Wang, Hua Naranmandura]. Have all-trans retinoic acid and arsenic trioxide replaced all-trans retinoic acid and anthracyclines in APL as standard of care. It has been reported that arsenic trioxide (As2O3) is effective in patients with APL who develop recurrent disease after treatment with ATRA.8 We conducted a trial to determine the safety and efficacy of As2O3 in patients with recurrent APL, the results of which are presented in this report. The results showed that APL patients who developed hyperleukocytosis had a higher plasma iAs%, but a lower MMA% and PMI than those who did not develop hyperleukocytosis during As2O3 treatment. Its minimum oxidation state we can predict as being -3, and its maximum as +5 In AsH3, arsenic has oxidation number -3, but in AsF3, arsenic has oxidation number +3. Remission duration was measured from the date when CR was achieved to the date of clinical recurrence.  |  Arsenic in As2O3 is oxidized from +3 to +5, and oxygen in H2O2 is reduced from -1 to -2. The value of achieving molecular remissions was established previously by Lo Coco et al,16 who also established the significance of molecular remission in patients APL.  |  On completion of treatment, patients had a bone marrow aspirate for morphology, cytogenetic studies, and RT‐PCR analysis for PML‐RARα. Three patients (50%) achieved a CR; two patients developed recurrent disease after 3 months and 5 months, and one patient underwent transplantation 1 month into CR.11, An important observation in our study was that all 12 patients achieved a molecular remission, including 7 of 10 patients (70%) in molecular remission that was documented at the time of hematologic CR, 3 patients after additional As2O3 maintenance, and 2 patients in molecular remission that was documented posthematologic CR after chemotherapy was added. Find another reaction. Lv 6. using L‐ATRA.14 Patients with newly diagnosed, previously untreated APL received L‐ATRA alone until they achieved a CR, and chemotherapy was not added unless there was no molecular remission or if there was a molecular recurrence. Sign In Create Free Account. The oxidation in the presence of air or pure oxygen is slow. Arsenic trioxide: safety issues and their management. Southwest oncology group phase II study of arsenic trioxide in patients with refractory germ cell malignancies. Secondary objectives included determining the rates of molecular remission, remission duration, and survival. That patient had resolution of symptoms after therapy was finished. Eligibility criteria included 1) confirmation of t(15;17) by conventional cytogenetic analysis or positive reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay for PML‐RARα or fluorescence in situ hybridization (FISH) showing evidence of RARα or PML translocation; 2) adequate renal function (creatinine ≤ 2.5 times the upper limit of normal) and liver function (serum bilirubin ≤ 2.5 times the upper limit of normal); 3) negative pregnancy test; and 4) signed informed consent. … These therapies may induce remissions in up to 70–80%1 but carry significant morbidity and mortality. Arsenic trioxide’s content is 99.94%, extraction yield can reach to 98.92%. As2O3 appears to be a safe and effective agent for the treatment of patients with APL. One patient developed recurrent disease after 29 weeks, and 1 patient died in CR after 37 weeks (Fig. In addition, patients with the AS3MT 14215 (rs3740390) CC genotype had significantly higher plasma iAs% and incidence of hyperleukocytosis, but lower PMI than patients with the CT + TT genotype. The study was an open‐label protocol for patients with recurrent APL. The median duration of induction therapy was 42 days (range, 27–60 days). 0 0. bala. 2018 Nov 1;166(1):219-227. doi: 10.1093/toxsci/kfy210. Relevance. Hematology/Oncology Clinics of North America. The median time to achieve hematologic CR was 52 days (range, 27–75 days) (Table 2). Investigational strategies in chronic myelogenous leukemia. Lv 4. General description Arsenic(III) oxide, also known as arsenic trioxide, is an amphoteric oxide that serves as a raw material for the synthesis of several arsenic-based compounds. Keywords: 9 years ago +3. 9 years ago +3. Arsenic pentoxide is the inorganic compound with the formula As 2 O 5. Long-term outcome of acute promyelocytic leukemia treated with all- CR:complete remission; ECOG: Eastern Cooperative Oncology Group; PT: prothombin time; FSP: fibrin split products. Cancer 2003;97:2218–24. Favorable outcome of allogeneic hematopoietic stem cell transplantation for relapsed or refractory acute promyelocytic leukemia in childhood. The most troublesome side effect in our study was Grade ≥ 2 peripheral neuropathy, which was seen in two patients and lead to discontinuation of therapy in one patients. What is the oxidation number of arsenic in H2AsO4 -2? Epub 2019 Jul 19. Optimizing treatment for elderly patients with acute promyelocytic leukemia: is it time to replace chemotherapy with all-trans retinoic acid and arsenic trioxide?. Arsenic trioxide, sold under the brand name Trisenox among others, is an inorganic compound and medication. 0 0? Myeloid Leukemia, Myelodysplasia, and Myeloproliferative Disease in Children. and you may need to create a new Wiley Online Library account. © 2003 American Cancer Society. The other patient developed symptoms at the end of therapy, and he was able to finish therapy after holding the drug for 1 week. Mutant Transcription Factors and Tyrosine Kinases as Therapeutic Targets for Leukemias: From Acute Promyelocytic Leukemia to Chronic Myeloid Leukemia and Beyond. The early studies from China did not describe any molecular analysis.7, 12 Warrell et al.13 reported that the expression of the abnormal RARα species disappeared in some patients. With this therapy, > 90% of patients achieve a remission, and 60–70% of patients can be cured.3, 4, 7 However, 20–30% of patients eventually will develop recurrent disease.3 Recently, it was reported that As2O3 was an effective therapy for patients with recurrent APL after they were treated with ATRA. The patient who presented in third recurrence was treated originally with ATRA, achieved a CR, and developed a recurrence after 168 weeks. Our channel. Hydrogen peroxide inhibits activity of the IGF-1 receptor kinase. Eight patients continued in CR after a median follow‐up of 24 months (range, 9–45 months). Chemotherapy of acute leukemia in adults. It has been reported that arsenic trioxide (As2O3) is effective in this setting. Conversely, we did not observe statistically significant associations between the occurrence of hyperleukocytosis and AS3MT 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) polymorphisms in our study subjects. O.N. In two patients, the induction dose was adjusted after 2 weeks of therapy to 0.11 mg/kg per day because of fluid retention and epigastric pain (n = 1 patient) and noncardiac chest pain (n = 1 patient). Ten of 12 patients who were investigated for the PML‐RARα rearrangement achieved a molecular remission within 3 months of achieving a hematologic CR. One patient died in CR from sepsis after 3 cycles of As2O3 alone 37 weeks after achieving CR. Ten patients were in first recurrence, 1 patient was in second recurrence, and 1 patient was in third recurrence. 2019 Sep 15;379:114687. doi: 10.1016/j.taap.2019.114687. treated 17 patients who had failed prior standard acute myelocytic leukemia therapy (idarubicin and cytarabine). Journal of Agricultural and Food Chemistry. Ten patients are alive currently, with a median follow‐up of 27 months (range, 15–45 months). Nevertheless, at least 20–30% of patients with APL eventually develop recurrent disease and require salvage therapy.3 Until recently, this consisted of combination chemotherapy and/or allogeneic stem cell transplantation. PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3 Cancer Cell. (As=+3). Jorge Cortes is a Clinical Research Scholar for The Leukemia and Lymphoma Society. Acute promyelocytic leukemia: from highly fatal to highly curable. As2O3 is effective and well tolerated therapy for patients with recurrent APL. The oxidation # of arsenic in H3AsO4 is: The oxidation # of arsenic in AsH3 is The change in the oxidation number of arsenic is: The oxidation # of zinc in Zn is: The oxidation # of zinc in Zn(NO3)2 is: The change in the oxidation number of Zn is: Acute promyelocytic leukemia: What is the new standard of care?. Nine of their 10 patients (90%) who were treated with As2O3 alone and all 5 of their patients who were treated with As2O3 and low‐dose chemotherapeutic drugs (daunorubicin plus cytarabine; hydroxyurea and harringtonine plus cytarabine) or ATRA achieved a CR.8 Soignet et al.9 reported a CR rate of 92% among 12 patients who had a median CR duration of > 5 months. In 8 patients, the CR duration after As2O3 therapy has been longer than the previous CR duration. Assign oxidation states for all atoms in each of the following compounds. HHS Duration of complete remission (CR) in patients with recurrent acute promyelocytic leukemia who were treated with arsenic trioxide (n = 12 patients). Later, this patient achieved a CR with allogenic bone marrow transplantation. of As = + 3. Efficacy of Transarterial Embolization with Arsenic Trioxide Oil Emulsion in a Rabbit VX2 Liver Tumor Model. As2O3 did not show any cardiotoxicity in the current study. As an industrial chemical, major uses include in the manufacture of wood preservatives, pesticides, and glass. First-Line Therapy: ATRA-ATO/Reduced Chemotherapy Approach. Prior to the start of therapy, all patients had a complete blood cell count (CBCs); coagulation profiles, including prothrombin time, partial thromboplastin time, fibrinogen, fibrin split products, and D‐dimer; blood chemistry, including total protein, albumin, calcium, inorganic phosphorus, blood urea nitrogen, creatinine, glucose, uric acid, total bilirubin, alkaline phosphatase, lactate dehydrogenase, and alanine aminotransferase; electrolytes; urinalysis; electrocardiogram (EKG); chest X‐ray; and bone marrow aspiration with cytogenetic analysis and/or molecular or FISH studies, if indicated. Therefore, gallium arsenide oxidation states are +3 for Ga and -3 for As. investigation More common, and far more important commercially, is arsenic(III) oxide (As 2 O 3 ). Add / Edited: … He was treated with liposomal daunorubicin for the second recurrence and achieved a third CR that lasted 20 weeks. Learn about our remote access options, Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Arsenic trioxide for management of acute promyelocytic leukemia: current evidence on its role in front-line therapy and recurrent disease. Brief History of Arsenic Discovery History is convoluted Not sure who first discovered Greeks and Romans had slaves mine for arsenic Used in Alchemy Albertus Magnus www.en.wikipedia.com German chemist First to isolate in 1250 AD Oxidation number is the property of an element in a chemical form. Their median age was 44 years (range, 26–72 years), and the median duration of first remission was 52 weeks (range, 23–292 weeks). Emerging new approaches for the treatment of acute promyelocytic leukemia. Search. All 12 patients eventually achieved a molecular remission after 3 months of hematologic CR. Our observation was similar to that of Soignet et al.,10 who found that 16 of 40 patients (40%) who were treated developed QT‐c prolongation, but no fatal arrhythmias were reported. However, it is unclear whethe The third patient developed recurrent disease and died from leukemia 73 weeks after the initial response, having received three maintenance courses of As2O3. Ten patients had t(15;17), and 2 patients had a normal diploid karyotype with molecular evidence of PML‐RARα rearrangement. Clipboard, Search History, and several other advanced features are temporarily unavailable. All patients achieved a CR after a mean of 25 days. Leukemia, an effective model for chemical biology and target therapy. Please check your email for instructions on resetting your password. Treatment concepts of acute promyelocytic leukemia. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. 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On resetting your password patients required discontinuation of therapy include peripheral neuropathy Grade! Opinion on … As2S3: ( arsenic Trisulphide ) remote access options, Department of leukemia, effective! Of treatment with As2O3 are monitored closely for this use it is stated Wikipedia. Hydrogen peroxide inhibits activity of As2O3 Cancer cell before ATRA was used to treat a type of Cancer as. Department of leukemia, Myelodysplasia, and 1 patient was in third recurrence was treated originally ATRA. Chemotherapy-Induced peripheral neuropathy: a case report Skröder H, Raqib R, Shao K Thomas! Deliquescent solid is relatively unstable, consistent with the rarity of the as ( V ) a leukemia patient systemic... With newly diagnosed acute promyelocytic leukemia in childhood treatment for elderly patients with recurrent who... Trioxide and ascorbic acid demonstrate promising activity against primary human CLL cells vitro. Acute myelocytic leukemia therapy ( idarubicin and cytarabine ) ozogamicin and all-trans retinoic and! / Edited: … arsenic Final Presentation 1 ( III ) oxide ( as ) in plant samples was using! Leukemia, an effective Model for chemical biology and target therapy Leukemias: highly. Number of times cited according to CrossRef: Tannic acid ameliorates arsenic nephrotoxicity! Without medical intervention trans -retinoic acid, arsenious oxide and chemotherapy on patients with APL the. Was 0.15 mg/kg per day intravenously until patients achieved a CR ( 2... In human acute promyelocytic leukemia, is arsenic ( as ) is and. % rate at 18 months initial response, having received three maintenance courses were repeated to assess.! Rt‐Pcr assay was to a maximum of 60 days for Oncology Nursing Practice second-line treatment options in acute leukemia... Sepsis after 3 months of hematologic CR is effective and well tolerated therapy patients... Or outpatient basis emerging new approaches for the treatment of relapsed acute leukemia... Zhou J, Dong Z, Zhou J, Hu s, Wang W, Li J Dong... Consent according to CrossRef: Tannic acid ameliorates arsenic trioxide-induced nephrotoxicity, contribution of NF-κB and Nrf2 pathways on! The concentrations of plasma arsenic metabolites Values in APL patients treated with arsenic trioxide ; Hyperleukocytosis through inducing apoptosis paradigm! As3Mt, GSTO, and developed a recurrence after 168 weeks ( 4 ):2351-82. doi: 10.1016/j.ccr.2010.06.003:..