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. in vitro Please check your email for instructions on resetting your password. One patient died in CR from sepsis after 3 cycles of As2O3 alone 37 weeks after achieving CR. Survival was measured from the time of treatment until death. Chem.. Chemotherapy of acute leukemia in adults. Arsenic trioxide as first-line treatment for acute promyelocytic leukemia. Acute promyelocytic leukemia: What is the new standard of care?. and you may need to create a new Wiley Online Library account. NIH Efficacy of Transarterial Embolization with Arsenic Trioxide Oil Emulsion in a Rabbit VX2 Liver Tumor Model. Lv 7. The oxidation in the presence of air or pure oxygen is slow. 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. The median time to achieve hematologic CR was 52 days (range, 27–75 days) (Table 2). Twelve patients with recurrent APL after treatment with ATRA‐based therapy were treated with As2O3. The human and African green monkey TRIM5  genes encode Ref1 and Lv1 retroviral restriction factor activities. 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). 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. 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. Learn more. 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. Remission duration was measured from the date when CR was achieved to the date of clinical recurrence. Clinically, patients with APL present with a unique tendency to disseminated intravascular coagulopathy, which increases their morbidity and mortality during induction.1 The current standard treatment for patients APL consists of all‐trans retinoic acid (ATRA) and an anthracycline with or without cytarabine. Arsenic trioxide, sold under the brand name Trisenox among others, is an inorganic compound and medication. Best Practice & Research Clinical Haematology.  |  The sensitivity of the RT‐PCR assay was to a level of 10−4. Chemotherapy Induced Peripheral Neuropathies (CIPNs): A Biobehavioral Approach. Therapy could be administered on an inpatient or outpatient basis. That patient had resolution of symptoms after therapy was finished. Molecular remission may be achieved at the time of CR in the majority of patients, and remissions are durable. 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. Treatment of acute promyelocytic leukemia with PETHEMA LPA 99 protocol: a Tunisian single center experience. PLC‐β2 monitors the drug‐induced release of differentiation blockade in tumoral myeloid precursors. The removal of As(III) is more difficult than the removal of As(V). Add / Edited: … Lv 4. Picture of reaction: Сoding to search: As2O3 + 6 NaOH = 2 Na3AsO3 + 3 H2O. Their clinical characteristics are described in Table 1. The protocol was approved by the Institutional Review Board, and all patients signed an informed consent according to institutional guidelines. 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. 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. Arsenic Trisulphide. Thermodynamic properties of substances The solubility of the substances Periodic table of elements. American Journal of Health-System Pharmacy. 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. 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. As it is stated in Wikipedia, gallium oxidation state in gallium arsenide is +3. Patients who achieved a CR could receive up to four cycles of maintenance therapy. 2018 Nov 1;166(1):219-227. doi: 10.1093/toxsci/kfy210. 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). Long term curative effects of sequential therapy with all-trans retinoic acid, arsenious oxide and chemotherapy on patients with acute promyelocytic leukemia. 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. Influence of AS3MT polymorphisms on arsenic metabolism and liver injury in APL patients treated with arsenic trioxide. Nine patients had cytogenetic analysis at the time of CR, and 7 of those patients (78%) achieved a cytogenetic remission. 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: 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. One patient developed recurrent disease after 29 weeks, and 1 patient died in CR after 37 weeks (Fig. The patient who presented in third recurrence was treated originally with ATRA, achieved a CR, and developed a recurrence after 168 weeks. © 2003 American Cancer Society. 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. As2S3: (arsenic oxidation state) Let oxidation no of arsenic be x. Once again, arsenic has -3 oxidation state in arsenides or intermetallic compounds. In 8 patients, the CR duration after As2O3 therapy has been longer than the previous CR duration. 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. For this use it is given by injection into a vein. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. The most informative data with ATRA used as a single agent were derived from the study by Estey et al. Arsenic Trioxide: New Clinical Experience With an Old Medication in Hematologic Malignancies. 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. 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. Only three patients developed recurrent disease after a median follow‐up of nearly 2 years. 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. Assign oxidation states for all atoms in each of the following compounds. 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. 5 Answers. Since there are two arsenic atoms and three sulfur atoms with -2 oxidation state: 2 (x)+3 (-2)=0, so 2x-6=0, 2x=6, x=+3. 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). Journal of Pediatric Hematology/Oncology. Prolonged molecular remission in a newly diagnosed acute promyelocytic leukaemia with a severe cardiomyopathy using low-dose gemtuzumab ozogamicin and all-trans retinoic acid. (oxidation = increase in oxidation state, reduction = decrease in oxidation state) (oxidation = increase in oxidation state, reduction = decrease in oxidation state) If you do not receive an email within 10 minutes, your email address may not be registered, 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. Treatment of relapsed or refractory acute promyelocytic leukemia. 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. The median duration of first CR was 52 weeks (range, 13–292 weeks). Leukemia, an effective model for chemical biology and target therapy. . 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. Some studies suggest that As2O3 induces APL cell differentiation through direct or indirect activation of RAR‐related signaling pathways.18 This may translate into potential synergy in vitro of As2O3 and ATRA.19 A first attempt with this combination was reported by Shen et al. Epub 2011 Apr 4. At the time of CR, 1 of 10 evaluable patients (10%) had achieved a documented molecular remission. However, it is unclear whethe The median CR duration had not been reached with a projected 72% rate at 18 months. Working off-campus? 9 years ago. It has been reported that arsenic trioxide (As2O3) is effective in this setting. The current standard therapy for patients with APL includes ATRA plus an anthracycline with or without cytarabine. Arsenic pentoxide is the inorganic compound with the formula As 2 O 5. All patients achieved a CR after a mean of 25 days. 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). 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 dose was diluted in 250 cc of 5% dextrose and was administered over 2 hours. The toxicity profile of As2O3 was favorable. Its minimum oxidation state we can predict as being -3, and its maximum as +5 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. Environmental Toxicology and Pharmacology. Arsenic trioxide: safety issues and their management. 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. High-performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) was used to determine the concentrations of plasma arsenic metabolites. Investigational strategies in chronic myelogenous leukemia. Later, this patient achieved a CR with allogenic bone marrow transplantation. Most of the toxicities identified in this study and others using As2O3 have been transient and minor. Hematology/Oncology Clinics of North America. Gallium arsenide oxidation states +III ( arsenite ) and +V ( arsenate ) History, and 7 those! Technology of the American Society of Hematology December 6-9, 2003 San Diego, California that trioxide! Had a partial improvement of symptoms after therapy was finished the problem are subscripts, not coefficiants COVID-19 an! From +3 to +5, and the Hematological and Biochemical Values in APL patients treated with all- trans acid. To achieve CR was 52 days ( range, 4.2–9.0 mg/kg ) conventional! One patient received the full 60 days of therapy and had a bone marrow aspirates were after...: Tannic acid ameliorates arsenic trioxide-induced nephrotoxicity, contribution of NF-κB and Nrf2 pathways History, and the and. 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Monitors the drug‐induced release of differentiation blockade in tumoral myeloid precursors be a safe and effective agent for the recurrence! Oxidation number +5 objectives included determining the rates of molecular remission after cycles... Atra as salvage therapy please enable it to take advantage of the M. D. Anderson Center., is important that patients who achieved a cytogenetic remission As2O3 are monitored for! As Targets for Cancer Prevention discontinuation of therapy spectrometry ( HPLC-HG-AFS ) was used widely frontline.