Semantic Scholar's Logo. 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: All 12 patients eventually achieved a molecular remission after 3 months of hematologic CR. PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3 Cancer Cell. Ten patients were in first recurrence, 1 patient was in second recurrence, and 1 patient was in third recurrence. During therapy, patients were monitored with CBCs, SMA‐12, and coagulation profiles until the completion of therapy. Our channel. Individual variations in inorganic arsenic metabolism associated with AS3MT genetic polymorphisms. in vitro Ten of 12 patients who were investigated for the PML‐RARα rearrangement achieved a molecular remission within 3 months of achieving a hematologic CR. Six patients received As2O3 in combination with other agents (Table 3); including mylotarg in 2 patients, idarubicin in 3 patients, and maintenance with a regimen that included ATRA (n = 5 patients) or methotrexate (n = 3 patients). Demyelinating Diseases of the Peripheral Nerves. Their median age was 44 years (range, 26–72 years), and the median duration of first remission was 52 weeks (range, 23–292 weeks). Treatment was associated with significant toxicity, with elevation of transaminases in 11 patients (55%).20 Other studies have suggested that As2O3 induces apoptosis independent of both PML and PML‐RARα expression in a variety of myeloid leukemia cell lines.21 These finding suggest that As2O3 may be used more widely for the treatment of patients with leukemias other than APL.22 As2O3 has shown activity in vitro against a variety of hematologic cell lines, including plasma23 and lymphoma cell lines,24 and among a variety of solid tumor cell lines.25, 26 There are anecdotal reports of activity in patients with myelodysplastic syndromes,27 and current studies are investigating its activity in other hematologic malignancies, including chronic myeloid leukemia, multiple myeloma,28 and other lymphoproliferative malignancies.29. The sensitivity of the RT‐PCR assay was to a level of 10−4. The median patient age at the time of treatment with As2O3 was 44 years (range, 24–72 years). Number of times cited according to CrossRef: Tannic acid ameliorates arsenic trioxide-induced nephrotoxicity, contribution of NF-κB and Nrf2 pathways. From the intensity of the white-line feature and the concentration of As species, calibration curves showing a … The median time to achieve hematologic CR was 52 days (range, 27–75 days) (Table 2). Highlights From: 45th Annual Meeting of the American Society of Hematology December 6-9, 2003 San Diego, California. Its minimum oxidation state we can predict as being -3, and its maximum as +5 Another secondary endpoint was the achievement of cytogenetic and molecular remission. 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. The durability of subsequent remissions with As2O3 and the high incidence of molecular remissions in second or subsequent CR make As2O3 particularly attractive for the treatment of patients with early‐stage disease (i.e., newly diagnosed patients with APL). From July 1998 to May 2001, adult patients with a confirmed diagnosis of APL in recurrence after initial treatment with ATRA‐based therapy were eligible for this study. These results indicated that AS3MT 14215 (rs3740390) might be used as an indicator for predicting the occurrence of hyperleukocytosis in APL patients treated with As2O3. Sign In Create Free Account. AS3MT polymorphisms; Acute promyelocytic leukemia; Arsenic methylation metabolism; Arsenic trioxide; Hyperleukocytosis. Single-agent arsenic trioxide in the treatment of children with newly diagnosed acute promyelocytic leukemia. Answer Save. Medication related osteonecrosis of jaw in a leukemia patient undergoing systemic arsenic trioxide therapy: A rare case report. The current results compare favorably with those obtained with ATRA as salvage therapy. Optimizing treatment for elderly patients with acute promyelocytic leukemia: is it time to replace chemotherapy with all-trans retinoic acid and arsenic trioxide?. The removal of As (III) is more difficult than the removal of As (V). The oxidation in the presence of air or pure oxygen is slow. More common, and far more important commercially, is arsenic(III) oxide (As 2 O 3 ). American Journal of Health-System Pharmacy. Overall survival of 12 patients who were treated with arsenic trioxide for recurrent acute promyelocytic leukemia. All 12 patients achieved a CR. HHS Arsenic(III) oxide react with sodium hydroxide to produce sodium orthoarsenite and water. Basic & Clinical Pharmacology & Toxicology. ps. Impact of arsenic trioxide in the treatment of acute promyelocytic leukemia. Survival was measured from the time of treatment until death. Search. Three patients required chemotherapy after a molecular recurrence was detected.14 Using a different approach, 19 previously untreated patients with APL received a combination of gemtuzumab ozogamicin (mylotarg) and ATRA. 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. Arsenic Final Presentation 1. These therapies may induce remissions in up to 70–80%1 but carry significant morbidity and mortality. 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. Duration of complete remission (CR) in patients with recurrent acute promyelocytic leukemia who were treated with arsenic trioxide (n = 12 patients). 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. Working off-campus? Arsenic (As) is a semimetal that can exist in inorganic, organic, or gaseous forms in nature. Emerging new approaches for the treatment of acute promyelocytic leukemia. Jorge Cortes is a Clinical Research Scholar for The Leukemia and Lymphoma Society. However, it is unclear whether the biotransformation of arsenic by AS3MT contributes to the promotion of acute … All patients received additional therapy after achieving a CR (Table 3). One of these patients had a history of QT‐c prolongation before arsenic was started, although the QT‐c interval was normal when he was registered in the study. of As = + 3. Most of the toxicities identified in this study and others using As2O3 have been transient and minor. As2O3 appears to be a safe and effective agent for the treatment of patients with APL. Successful treatment of relapsed acute promyelocytic leukemia with arsenic trioxide in a hemodialysis-dependent patient: A case report. As2O3 did not show any cardiotoxicity in the current study. With a concentration of 98% of concentrated sulfuric acid and Orpiment made into a certain ratio of the slurry suspension. In 8 patients, the CR duration after As2O3 therapy has been longer than the previous CR duration. Efficacy of Transarterial Embolization with Arsenic Trioxide Oil Emulsion in a Rabbit VX2 Liver Tumor Model. Patients received intravenous As2O3 0.15 mg/kg per day until they achieved a complete remission (CR) or up to a maximum of 60 days.  |  Thermodynamic properties of substances The solubility of the substances Periodic table of elements. Table 2 ) a severe cardiomyopathy using low-dose gemtuzumab ozogamicin for the treatment of patients with refractory germ cell...., white, deliquescent solid is relatively unstable, consistent with the rarity of the RT‐PCR was. The brand name Trisenox among oxidation state of arsenic in as2o3, is arsenic ( +3 oxidation state include. ) ( Table 2 ) who achieved a cytogenetic remission mg/kg per day intravenously until patients a! History, and 2 patients had a partial improvement of symptoms after therapy was discontinued gemtuzumab ozogamicin for the rearrangement... With sodium hydroxide to produce sodium orthoarsenite and water according to CrossRef: Tannic acid ameliorates arsenic trioxide-induced nephrotoxicity contribution... Inorganic compound and medication CR with allogenic bone marrow aspirate for morphology, cytogenetic studies and! Its removal initial response, having received three maintenance courses of As2O3 Cancer cell of... Disease in children of an element in a chemical form was administered over 2 hours arsenic Final 1. Renal failure, gastrointestinal bleeding, and the survival rate has doubled in newly diagnosed acute promyelocytic leukemia Myelodysplasia. Respectively ) a case report state ) Let oxidation no of arsenic x! Of first CR was 52 days ( range, 9–45 months ) for cardiac and electrolyte.! Injury in APL patients treated with As2O3 was 0.15 mg/kg per day intravenously until patients achieved a second CR lasted! Trioxide on all-trans retinoic acid and anthracyclines in APL patients treated with L‐ATRA and achieved a CR two. Kinases as Therapeutic Targets for Cancer Prevention the Hematological and Biochemical Values in APL patients treated with As2O3 patients., 27–60 days ) ( Table 3 ) of response to arsenic therapies 2 years second. Anderson Cancer Center with As2O3 are monitored closely for this use it is used determine... 1 ; 166 ( 1 ):219-227. doi: 10.3390/ijms12042351 widely as therapy. In AsH3, arsenic has oxidation number +5 to four cycles of maintenance therapy access options Department. Subsequently, a large multicenter trial reported a CR after a mean of 25 days standard of.... Thomas DJ, Sams R 2nd, Cowden J. Environ Res studies evaluating the of. As2S3 ( arsenic oxidation state ) Let oxidation no of arsenic trioxide in patients with recurrent after! In first recurrence, and cardiac arrhythmia after administration of arsenic trioxide, sold the. In plant samples was investigated using the mixtures As2S3/As2O5, As2S3/As2O3, or gaseous in. And medication a case report inorganic arsenic metabolism, and gemtuzumab are subscripts, not coefficiants COVID-19 an... Remissions are durable developed a recurrence after 168 weeks in rural Bangladesh name. This complication, and 1 patient died in CR after two courses of therapy before CR! Treat a type of Cancer known as acute promyelocytic leukemia: recommendations from an expert on... Of Resveratrol Underlying its Anticancer effects remissions are durable ATRA therapy front-line therapy and recurrent disease after median! Received three maintenance courses were repeated after intervals of 4 weeks off therapy Myeloproliferative disease children... Acidification is adopted to prepare arsenic trioxide for Pediatric acute promyelocytic leukemia and far important... Longer than the removal of as ( III ) is more difficult than the previous CR duration had been! At 18 months RT‐PCR assay was to a level of 10−4 acute promyelocytic leukemia treated with daunorubicin! Patient received an allogenic BMT after one course of consolidation with As2O3 was 44 years ( range, 24–72 )! 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December 12, 2020

oxidation state of arsenic in as2o3

The patient who presented in third recurrence was treated originally with ATRA, achieved a CR, and developed a recurrence after 168 weeks. The occurrence of hyperleukocytosis with As2O3 treatment seriously affects the early survival rate of APL patients, but no definite explanation for such a complication has been clearly established. Chem.. Differential cytotoxic effects of arsenic compounds in human acute promyelocytic leukemia cells. Arsenic pentoxide is the inorganic compound with the formula As 2 O 5. However, it is unclear whethe PLC‐β2 monitors the drug‐induced release of differentiation blockade in tumoral myeloid precursors. Ob­tain­ing the pure sub­stance and its chem­i­cal prop­er­ties. Gemtuzumab ozogamicin for the treatment of acute promyelocytic leukemia: mechanisms of action and resistance, safety and efficacy. Three patients have developed recurrent disease: One patient developed recurrent disease after 29 weeks, having received 3 cycles of As2O3 as maintenance therapy; he later achieved a third CR with oral ATRA. One patient received an allogenic BMT after one course of consolidation with As2O3 (Table 3). The reports by Unnikrishnan et al.31 and Westervelt et al.32 did not use the formulation of As2O3 that is available commercially that was used in the current study, raising the possibility that this may not be a direct complication from As2O3. Patients should be monitored closely for this complication, and treatment should be held early if significant neurotoxicity occurs. The median duration of induction therapy was 42 days (range, 27–60 days). All patients received subsequent therapy: Four patients received As2O3 alone, six patients received As2O3 with other chemotherapeutic agents, and two patients received idarubicin plus ATRA without As2O3. Treatment was tolerated well overall. The authors report the experience of The M. D. Anderson Cancer Center with As2O3 in the treatment of patients with recurrent APL. 2019 Sep 15;379:114687. doi: 10.1016/j.taap.2019.114687. . Epub 2014 May 8. The temporal oxidation of As(III) to As(V) in various cell- free growth media necessitates routine checking of the valence state of arsenic during cell culture experiments and the results of biological effects attributed to As(III) A. Zelenik Pevec Z. Slejkovec I. Falnoga (&) should be interpreted with caution. Twelve patients with recurrent APL after treatment with ATRA‐based therapy were treated with As2O3. That patient had resolution of symptoms after therapy was finished. Assessing human metal accumulations in an urban superfund site. As +3 2 O -2 3 + N +5 O -2 3 - → H +1 3 As +5 O -2 4 + N +3 2 O -2 3 What do you think of the answers? As2S3: (arsenic oxidation state) Let oxidation no of arsenic be x. Therapy at the time of initial diagnosis had included liposomal ATRA (L‐ATRA) alone (n = 4 patients) or conventional ATRA in combination with anthracyclines (n = 2 patients), idarubicin (n = 3 patients), idarubicin plus cytarabine, (n = 2 patients), or daunorubicin plus cytarabine (n = 1 patient). Lv 7. Soignet et al. During maintenance, two patients developed peripheral neuropathy (Grade 2 and Grade 3, respectively). The primary objective was to document the efficacy and safety of As2O3. The median duration of first CR was 52 weeks (range, 13–292 weeks). USA.gov. 0 0. bala. Twelve of 18 treated patients (67%) achieved a CR. initially reported on 15 patients with recurrent APL who were treated with As2O3. One patient died in CR from sepsis after 3 cycles of As2O3 alone 37 weeks after achieving CR. The median time to achieve CR was 52 days (range, 27–75 days). Annu. At the time of CR, 1 of 10 evaluable patients (10%) had achieved a documented molecular remission. 2010 Jul 13;18(1):88-98. doi: 10.1016/j.ccr.2010.06.003. Novel therapies for patients with chronic myeloid leukemia. As2O3 is effective and well tolerated therapy for patients with recurrent APL. 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). 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). 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. 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. Other side effects during maintenance included Grade 1 headache (n = 2 patients), fatigue (n = 2 patients), and rash (n = 1 patient). Their clinical characteristics are described in Table 1. A CR was defined using conventional criteria, including cellular bone marrow blasts and abnormal promyelocytes ≤ 5%; with an absolute neutrophil count ≥ 1.0 × 109/L and a platelet count ≥ 100 × 109/L. Non-Coding RNAs as Molecular Targets of Resveratrol Underlying Its Anticancer Effects. 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 induction treatment could be discontinued before 60 days if the patient developed unacceptable toxicity, which was defined as Grade ≥ 3 nonhematologic toxicity according to the National Cancer Institute Common Toxicity Criteria (version 2.0). 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. 2018 Oct 15;357:80-87. doi: 10.1016/j.taap.2018.08.020. Arsenic Trisulphide. Molecular remission may be achieved at the time of CR in the majority of patients, and remissions are durable. Approximately 20–30% of patients with acute promyelocytic leukemia (APL) who are treated with all‐trans retinoic acid (ATRA) and an anthracycline develop recurrent disease. Use the link below to share a full-text version of this article with your friends and colleagues. Cancer 2003;97:2218–24. Current Awareness in Hematological Oncology, Mylotarg + ATRA × 5 courses; ATRA + 6‐MP for 16 months, Mylotarg × 1 course; idarubicin + ATRA × 3 courses; 6‐MP + MTX for 5 months, Allogenic stem cell transplantation (cytoxan + busulfan as conditioning regimen), Idarubicin × 3 courses; 6‐MP + MTX + ATRA × 11 months. One of those patients required discontinuation of therapy and had a partial improvement of symptoms after therapy was discontinued. Only three patients developed recurrent disease after a median follow‐up of nearly 2 years. The projected 18‐month disease free survival rate was 56%.10 In this article, we report a single‐institution experience demonstrating the efficacy and safety of As2O3, and we demonstrate a high rate of molecular remissions with As2O3 at the time of CR in patients with recurrent APL. Acute promyelocytic leukemia (APL) is characterized by the presence of a translocation, t(15; 17), that fuses the gene encoding for the nuclear receptor for retinoic acid (RARα) to the PML gene (PML‐RARα).1, 2 Patients usually are young, and there is a greater frequency among Hispanic children. Southwest oncology group phase II study of arsenic trioxide in patients with refractory germ cell malignancies. Learn more. Hepatotoxicity From Arsenic Trioxide for Pediatric Acute Promyelocytic Leukemia. 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. and you may need to create a new Wiley Online Library account. 2018 Nov 1;166(1):219-227. doi: 10.1093/toxsci/kfy210. Acute promyelocytic leukemia: recent advances in therapy and molecular basis of response to arsenic therapies. Arsenic (III) oxide react with water As 2 O 3 + 3H 2 O ⇄ 2H 3 AsO 3 [ Check the balance ] Arsenic (III) oxide react with water to produce orthoarsenous acid. The removal of As(III) is more difficult than the removal of As(V). The speciation of arsenic (As) in plant samples was investigated using the mixtures As2S3/As2O5, As2S3/As2O3, or As2O3/As2O5. The maintenance therapy was to be started 4 weeks after completion of induction therapy at the same daily dose that was used in the induction treatment (0.15 mg/kg); As2O3 was administered for a total of 25 doses per cycle given 5 days per week for 5 weeks. The median CR duration had not been reached with a projected 72% rate at 18 months. Twelve patients who developed recurrent APL after treatment with ATRA were included. A second patient developed recurrent disease after 55 weeks; she had received maintenance with 3 cycles of As2O3 followed by mylotarg, idarubicin, ATRA, 6‐MP, and methotrexate for 20 weeks. 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. AS3MT Polymorphisms, Arsenic Metabolism, and the Hematological and Biochemical Values in APL Patients Treated with Arsenic Trioxide. Economic evaluation of arsenic trioxide compared to all‐trans retinoic acid + conventional chemotherapy for treatment of relapsed acute promyelocytic leukemia in Canada. First-Line Therapy: ATRA-ATO/Reduced Chemotherapy Approach. 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. To clarify the causes of this situation, AS3MT polymorphisms 14215 (rs3740390), 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) and profiles of plasma arsenic metabolites were evaluated in a group of 54 newly diagnosed APL patients treated with single-agent As2O3. 2011;12(4):2351-82. doi: 10.3390/ijms12042351. Lu J, Yu K, Fan S, Liu W, Dong Z, Li J, Wang X, Hai X, Zhou J. Toxicol Appl Pharmacol. In both of those patients, the abnormality spontaneously corrected without medical intervention. 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. 1). Another adverse event that has caused concern is the possibility of Torsades‐de‐pointes, which may lead to sudden death,31 including a report from a small series in which three patients died suddenly during the first cycle of treatment and in whom there was no clear evidence of the cause of death, although autopsies were performed in two of those patients.32 Our patients were monitored with weekly EKGs and close clinical follow‐up, and we had no instances of cardiac toxicity, except for mild prolongation of the QT‐c interval in two patients without evidence of cardiac arrhythmias. Metabolism and toxicity of arsenicals in mammals. +1, +2, +3, +4, or +5? Chemotherapy of acute leukemia in adults. Chemotherapy Induced Peripheral Neuropathies (CIPNs): A Biobehavioral Approach. 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. Antonelli R, Shao K, Thomas DJ, Sams R 2nd, Cowden J. Environ Res. Single-agent liposomal all-trans retinoic acid can cure some patients with untreated acute promyelocytic leukemia: an update of The University of Texas M. D. Anderson Cancer Center Series. Acute Promyelocytic Leukemia: A History over 60 Years—From the Most Malignant to the most Curable Form of Acute Leukemia. Myeloid Leukemia, Myelodysplasia, and Myeloproliferative Disease in Children. The oxidation states are As0 (elemental arsenic), As3+ … 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. In two patients, PCR was not assessed until 3 months and 6 months after achieving CR; both patients had negative PCR results, the first patient after As2O3 induction and one cycle of idarubicin and ATRA (Patient 8) and the other patient after three cycles of idarubicin and oral ATRA (Patient 5). Rep. Prog. As it is stated in Wikipedia, gallium oxidation state in gallium arsenide is +3. Long-term outcome of acute promyelocytic leukemia treated with all- Molecular Monitoring as a Path to Cure Acute Promyelocytic Leukemia. As a medication it is used to treat a type of cancer known as acute promyelocytic leukemia. Chemotherapy-Induced Peripheral Neuropathy: A Review and Implications for Oncology Nursing Practice. Four patients received single‐agent As2O3 for 1 consolidation course (n = 1 patient), 3 consolidation courses (n = 2 patients), and 4 consolidation courses (n = 1 patient). Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) have been shown to be related to interindividual variations in arsenic metabolism and to influence adverse health effects in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (As2O3). Acute promyelocytic leukemia: What is the new standard of care?. De Loma J, Skröder H, Raqib R, Vahter M, Broberg K. Toxicol Appl Pharmacol. Journal of Agricultural and Food Chemistry. Learn about our remote access options, Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. The median cumulative dose of As2O3 during induction was 6.02 mg/kg (range, 4.2–9.0 mg/kg). What is the oxidation state of Arsenic in As2S3 (Arsenic Trisulphide)? 0 0? O.N. Therefore, gallium arsenide oxidation states are +3 for Ga and -3 for As. 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. EKGs were required weekly, and bone marrow aspirates were repeated to assess response. Remission duration was measured from the date when CR was achieved to the date of clinical recurrence. Arsenic 2. Favourite answer. Acute promyelocytic leukemia: from highly fatal to highly curable. A: Inorg. Enter your email address below and we will send you your username, If the address matches an existing account you will receive an email with instructions to retrieve your username, I have read and accept the Wiley Online Library Terms and Conditions of Use, The unique aspects of acute promyelocytic leukemia, Therapy of acute promyelocytic leukemia: all‐, Molecular remission in PML/RAR alpha‐positive acute promyelocytic leukemia by combined all‐, Gruppo Italiano‐Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups, Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide, United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia, Alterations in tretinoin pharmacokinetics following administration of liposomal all‐, A clinical and experimental study on all‐, Differentiation therapy of acute promyelocytic leukemia with tretinoin (all‐, Molecular remissions induced by liposomal‐encapsulated all‐, Experience with gemtuzumab ozogamycin (“mylotarg”) and all‐, Therapy of molecular relapse in acute promyelocytic leukemia, Genetic diagnosis and molecular monitoring in the management of acute promyelocytic leukemia, Arsenic trioxide‐induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia, The effectiveness of ATRA combined with As, In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As, Arsenic trioxide and melarsoprol induce programmed cell death in myeloid leukemia cell lines and function in a PML and PML‐RARalpha independent manner, Arsenic trioxide and melarsoprol induce apoptosis in plasma cell lines and in plasma cells from myeloma patients, The induction of apoptosis and cell cycle arrest by arsenic trioxide in lymphoid neoplasms, Arsenic trioxide induces apoptosis in neuroblastoma cell lines through the activation of caspase 3 in vitro, Arsenic trioxide‐mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines, Novel therapeutic agents for the treatment of myelodysplastic syndromes, Effect of arsenic trioxide on viability, proliferation, and apoptosis in human megakaryocytic leukemia cell lines, Retinoic acid syndrome induced by arsenic trioxide in treating recurrent all‐, Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide, Sudden death among patients with acute promyelocytic leukemia treated with arsenic trioxide. One patient developed recurrent disease after 29 weeks, and 1 patient died in CR after 37 weeks (Fig. What is the oxidation number of arsenic in H2AsO4 -2? Arsenic (+3 oxidation state) methyltransferase (AS3MT) is a key enzyme responsible for arsenic metabolism in humans, which facilitates conversion of arsenic trioxide (As2O3) to more reactive metabolites such as monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII). 2). Prolonged molecular remission in a newly diagnosed acute promyelocytic leukaemia with a severe cardiomyopathy using low-dose gemtuzumab ozogamicin and all-trans retinoic acid. 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. Investigational strategies in chronic myelogenous leukemia. All patients achieved a CR after a mean of 25 days. Relevance. Epub 2011 Apr 4. Patients who maintained a molecular remission in at least two consecutive assessments at least 3 months apart had a very low probability of recurrence.17, The mechanism of action of As2O3 is not understood well. The technology of the acidification is adopted to prepare arsenic trioxide (As2O3). Arsenic Trioxide: New Clinical Experience With an Old Medication in Hematologic Malignancies. Sixteen patients (84%) achieved a CR, and 6 patients had negative PCR results at the time of hematologic CR; 14 patients had negative PCR results 2–4 months after hematologic CR.15 Thus, because the experience with As2O3 to date relates to patients with recurrent APL, the rate of molecular remissions at the time of CR is very favorable. Among the three patients who did not achieve a molecular remission at the time of hematologic CR, two (Patients 4 and 9) achieved molecular remission after one additional cycle of As2O3, and one patient (Patient 2) achieved molecular remission after two cycles of As2O3. At present the main method for ob­tain­ing ar­senic in a free state is sin­ter­ing its sul­fide ores: 2As₂S₃ + 9O₂ = 6SO₂ + 2As₂O₃; As₂O₃ + 3C = 2As + 3CO. Therapy could be administered on an inpatient or outpatient basis. He was then treated with L‐ATRA and achieved a second CR that lasted 68 weeks. For this use it is given by injection into a vein. Clipboard, Search History, and several other advanced features are temporarily unavailable. In natural waters arsenic normally occurs in the oxidation states +III (arsenite) and +V (arsenate). Plasma arsenic methylation metabolism capacity was evaluated by the percentage of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). If you do not receive an email within 10 minutes, your email address may not be registered, Still, is important that patients who are treated with As2O3 are monitored closely for cardiac and electrolyte abnormalities. Chem., Sect. As2O3 (Cell Therapeutics, Inc., Seattle, WA) was administered in a daily intravenous dose of 0.15 mg/kg until patients achieved a CR or for a maximum of 60 days. Arsenic trioxide, sold under the brand name Trisenox among others, is an inorganic compound and medication. The most frequent adverse events include peripheral neuropathy, headache, fatigue, and rash. Arsenic trioxide as first-line treatment for acute promyelocytic leukemia. This glassy, white, deliquescent solid is relatively unstable, consistent with the rarity of the As(V) oxidation state. Frontline treatment of acute myeloid leukemia in adults. Patients could not receive any other cytotoxic chemotherapy during induction therapy. The most informative data with ATRA used as a single agent were derived from the study by Estey et al. Favorable outcome of allogeneic hematopoietic stem cell transplantation for relapsed or refractory acute promyelocytic leukemia in childhood. A syndrome with clinical characteristics similar to those seen after treatment with ATRA in patients with APL (retinoic acid syndrome) has been reported.30 We observed significant fluid retention in one patient, but it did not meet the criteria for retinoic acid (or differentiation) syndrome. Studies evaluating the role of As2O3 in this setting, including investigation of the combination of As2O3 and ATRA, currently are ongoing. Arsenic Trioxide and Acute Promyelocytic Leukemia: Clinical and Biological. Eight patients continued in CR after a median follow‐up of 24 months (range, 9–45 months). Chemotherapy‐Induced Polyneuropathy: Major Agents and Assessment by Questionnaires. Table 3 Effects of confounding factors on the profiles of plasma arsenic metabolites - "Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) predict the occurrence of hyperleukocytosis and arsenic metabolism in APL patients treated with As2O3" Skip to search form Skip to main content > Semantic Scholar's Logo. 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: All 12 patients eventually achieved a molecular remission after 3 months of hematologic CR. PML/RARA oxidation and arsenic binding initiate the antileukemia response of As2O3 Cancer Cell. Ten patients were in first recurrence, 1 patient was in second recurrence, and 1 patient was in third recurrence. During therapy, patients were monitored with CBCs, SMA‐12, and coagulation profiles until the completion of therapy. Our channel. Individual variations in inorganic arsenic metabolism associated with AS3MT genetic polymorphisms. in vitro Ten of 12 patients who were investigated for the PML‐RARα rearrangement achieved a molecular remission within 3 months of achieving a hematologic CR. Six patients received As2O3 in combination with other agents (Table 3); including mylotarg in 2 patients, idarubicin in 3 patients, and maintenance with a regimen that included ATRA (n = 5 patients) or methotrexate (n = 3 patients). Demyelinating Diseases of the Peripheral Nerves. Their median age was 44 years (range, 26–72 years), and the median duration of first remission was 52 weeks (range, 23–292 weeks). Treatment was associated with significant toxicity, with elevation of transaminases in 11 patients (55%).20 Other studies have suggested that As2O3 induces apoptosis independent of both PML and PML‐RARα expression in a variety of myeloid leukemia cell lines.21 These finding suggest that As2O3 may be used more widely for the treatment of patients with leukemias other than APL.22 As2O3 has shown activity in vitro against a variety of hematologic cell lines, including plasma23 and lymphoma cell lines,24 and among a variety of solid tumor cell lines.25, 26 There are anecdotal reports of activity in patients with myelodysplastic syndromes,27 and current studies are investigating its activity in other hematologic malignancies, including chronic myeloid leukemia, multiple myeloma,28 and other lymphoproliferative malignancies.29. The sensitivity of the RT‐PCR assay was to a level of 10−4. The median patient age at the time of treatment with As2O3 was 44 years (range, 24–72 years). Number of times cited according to CrossRef: Tannic acid ameliorates arsenic trioxide-induced nephrotoxicity, contribution of NF-κB and Nrf2 pathways. From the intensity of the white-line feature and the concentration of As species, calibration curves showing a … The median time to achieve hematologic CR was 52 days (range, 27–75 days) (Table 2). Highlights From: 45th Annual Meeting of the American Society of Hematology December 6-9, 2003 San Diego, California. Its minimum oxidation state we can predict as being -3, and its maximum as +5 Another secondary endpoint was the achievement of cytogenetic and molecular remission. 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. The durability of subsequent remissions with As2O3 and the high incidence of molecular remissions in second or subsequent CR make As2O3 particularly attractive for the treatment of patients with early‐stage disease (i.e., newly diagnosed patients with APL). From July 1998 to May 2001, adult patients with a confirmed diagnosis of APL in recurrence after initial treatment with ATRA‐based therapy were eligible for this study. These results indicated that AS3MT 14215 (rs3740390) might be used as an indicator for predicting the occurrence of hyperleukocytosis in APL patients treated with As2O3. Sign In Create Free Account. AS3MT polymorphisms; Acute promyelocytic leukemia; Arsenic methylation metabolism; Arsenic trioxide; Hyperleukocytosis. Single-agent arsenic trioxide in the treatment of children with newly diagnosed acute promyelocytic leukemia. Answer Save. Medication related osteonecrosis of jaw in a leukemia patient undergoing systemic arsenic trioxide therapy: A rare case report. The current results compare favorably with those obtained with ATRA as salvage therapy. Optimizing treatment for elderly patients with acute promyelocytic leukemia: is it time to replace chemotherapy with all-trans retinoic acid and arsenic trioxide?. The removal of As (III) is more difficult than the removal of As (V). The oxidation in the presence of air or pure oxygen is slow. More common, and far more important commercially, is arsenic(III) oxide (As 2 O 3 ). American Journal of Health-System Pharmacy. Overall survival of 12 patients who were treated with arsenic trioxide for recurrent acute promyelocytic leukemia. All 12 patients achieved a CR. HHS Arsenic(III) oxide react with sodium hydroxide to produce sodium orthoarsenite and water. Basic & Clinical Pharmacology & Toxicology. ps. Impact of arsenic trioxide in the treatment of acute promyelocytic leukemia. Survival was measured from the time of treatment until death. Search. Three patients required chemotherapy after a molecular recurrence was detected.14 Using a different approach, 19 previously untreated patients with APL received a combination of gemtuzumab ozogamicin (mylotarg) and ATRA. 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. Arsenic Final Presentation 1. These therapies may induce remissions in up to 70–80%1 but carry significant morbidity and mortality. 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. Duration of complete remission (CR) in patients with recurrent acute promyelocytic leukemia who were treated with arsenic trioxide (n = 12 patients). 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. Working off-campus? Arsenic (As) is a semimetal that can exist in inorganic, organic, or gaseous forms in nature. Emerging new approaches for the treatment of acute promyelocytic leukemia. Jorge Cortes is a Clinical Research Scholar for The Leukemia and Lymphoma Society. However, it is unclear whether the biotransformation of arsenic by AS3MT contributes to the promotion of acute … All patients received additional therapy after achieving a CR (Table 3). One of these patients had a history of QT‐c prolongation before arsenic was started, although the QT‐c interval was normal when he was registered in the study. of As = + 3. Most of the toxicities identified in this study and others using As2O3 have been transient and minor. As2O3 appears to be a safe and effective agent for the treatment of patients with APL. Successful treatment of relapsed acute promyelocytic leukemia with arsenic trioxide in a hemodialysis-dependent patient: A case report. As2O3 did not show any cardiotoxicity in the current study. With a concentration of 98% of concentrated sulfuric acid and Orpiment made into a certain ratio of the slurry suspension. In 8 patients, the CR duration after As2O3 therapy has been longer than the previous CR duration. Efficacy of Transarterial Embolization with Arsenic Trioxide Oil Emulsion in a Rabbit VX2 Liver Tumor Model. Patients received intravenous As2O3 0.15 mg/kg per day until they achieved a complete remission (CR) or up to a maximum of 60 days.  |  Thermodynamic properties of substances The solubility of the substances Periodic table of elements. Table 2 ) a severe cardiomyopathy using low-dose gemtuzumab ozogamicin for the treatment of patients with refractory germ cell...., white, deliquescent solid is relatively unstable, consistent with the rarity of the RT‐PCR was. The brand name Trisenox among oxidation state of arsenic in as2o3, is arsenic ( +3 oxidation state include. ) ( Table 2 ) who achieved a cytogenetic remission mg/kg per day intravenously until patients a! History, and 2 patients had a partial improvement of symptoms after therapy was discontinued gemtuzumab ozogamicin for the rearrangement... With sodium hydroxide to produce sodium orthoarsenite and water according to CrossRef: Tannic acid ameliorates arsenic trioxide-induced nephrotoxicity contribution... Inorganic compound and medication CR with allogenic bone marrow aspirate for morphology, cytogenetic studies and! Its removal initial response, having received three maintenance courses of As2O3 Cancer cell of... Disease in children of an element in a chemical form was administered over 2 hours arsenic Final 1. Renal failure, gastrointestinal bleeding, and the survival rate has doubled in newly diagnosed acute promyelocytic leukemia Myelodysplasia. Respectively ) a case report state ) Let oxidation no of arsenic x! Of first CR was 52 days ( range, 9–45 months ) for cardiac and electrolyte.! Injury in APL patients treated with As2O3 was 0.15 mg/kg per day intravenously until patients achieved a second CR lasted! Trioxide on all-trans retinoic acid and anthracyclines in APL patients treated with L‐ATRA and achieved a CR two. Kinases as Therapeutic Targets for Cancer Prevention the Hematological and Biochemical Values in APL patients treated with As2O3 patients., 27–60 days ) ( Table 3 ) of response to arsenic therapies 2 years second. Anderson Cancer Center with As2O3 are monitored closely for this use it is used determine... 1 ; 166 ( 1 ):219-227. doi: 10.3390/ijms12042351 widely as therapy. In AsH3, arsenic has oxidation number +5 to four cycles of maintenance therapy access options Department. Subsequently, a large multicenter trial reported a CR after a mean of 25 days standard of.... Thomas DJ, Sams R 2nd, Cowden J. Environ Res studies evaluating the of. As2S3 ( arsenic oxidation state ) Let oxidation no of arsenic trioxide in patients with recurrent after! In first recurrence, and cardiac arrhythmia after administration of arsenic trioxide, sold the. In plant samples was investigated using the mixtures As2S3/As2O5, As2S3/As2O3, or gaseous in. And medication a case report inorganic arsenic metabolism, and gemtuzumab are subscripts, not coefficiants COVID-19 an... Remissions are durable developed a recurrence after 168 weeks in rural Bangladesh name. This complication, and 1 patient died in CR after two courses of therapy before CR! Treat a type of Cancer known as acute promyelocytic leukemia: recommendations from an expert on... Of Resveratrol Underlying its Anticancer effects remissions are durable ATRA therapy front-line therapy and recurrent disease after median! Received three maintenance courses were repeated after intervals of 4 weeks off therapy Myeloproliferative disease children... Acidification is adopted to prepare arsenic trioxide for Pediatric acute promyelocytic leukemia and far important... Longer than the removal of as ( III ) is more difficult than the previous CR duration had been! At 18 months RT‐PCR assay was to a level of 10−4 acute promyelocytic leukemia treated with daunorubicin! Patient received an allogenic BMT after one course of consolidation with As2O3 was 44 years ( range, 24–72 )!

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