{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T12:34:34Z","timestamp":1724416474871},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,3,22]],"date-time":"2001-03-22T00:00:00Z","timestamp":985219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2001,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Arsenic trioxide (As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>) effectively induces remissions in relapsed acute promyelocytic leukaemia (APL), but the safety of its long\u2010term administration is unknown. The anthracycline idarubicin is highly active alone or in combination chemotherapy for the treatment of APL. To minimize arsenic exposure and based on the high sensitivity of APL cells to anthracyclines, we conducted a prospective study to evaluate induction with As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> followed by consolidation with idarubicin in the treatment of APL in relapse. Eight patients were treated with As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> at a daily dose of 10 mg until remission, followed by three monthly courses of idarubicin, at 6 mg\/m<jats:sup>2<\/jats:sup>\/day for 5 days in the first course and 6 mg\/m<jats:sup>2<\/jats:sup>\/day for 2 days in the subsequent two courses. All patients achieved morphological but not molecular remission after As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> treatment. During As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> therapy, an increase in white cell count peaking at a median of 17 days occurred in all the cases. Serial flow cytometric analysis of apoptosis, with mitochondrial APO2.7 antigen expression and the sub\u2010G1 cell fraction on DNA histogram as markers, showed induction of apoptosis of APL cells in vivo. With both qualitative and real\u2010time quantitative polymerase chain reaction, all patients were shown to attain molecular remission after subsequent idarubicin treatment. With a median follow up of 13 months, seven of eight patients have remained in complete clinical remission, with six patients in molecular remission as well. One patient who was in third remission became PCR\u2010positive after being transiently negative. One patient died from an intracranial extramedullary relapse after achieving marrow molecular remission. We conclude that As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> induction followed by idarubicin consolidation is an effective therapy for APL in relapse. This regimen avoids the possible long\u2010term toxicities of As<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub> and mutagenicity of combination chemotherapy, a strategy that might be suitable for this potentially curable leukaemia. Am. J. Hematol. 66:274\u2013279, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.1057","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:27:27Z","timestamp":1030310847000},"page":"274-279","source":"Crossref","is-referenced-by-count":46,"title":["Arsenic trioxide\u2010 and idarubicin\u2010induced remissions in relapsed acute promyelocytic leukaemia: Clinicopathological and molecular features of a pilot study"],"prefix":"10.1002","volume":"66","author":[{"given":"Y.L.","family":"Kwong","sequence":"first","affiliation":[]},{"given":"W.Y.","family":"Au","sequence":"additional","affiliation":[]},{"given":"C.S.","family":"Chim","sequence":"additional","affiliation":[]},{"given":"A.","family":"Pang","sequence":"additional","affiliation":[]},{"given":"C.","family":"Suen","sequence":"additional","affiliation":[]},{"given":"R.","family":"Liang","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2001,3,22]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1182\/blood.V76.9.1704.1704","article-title":"all\u2010trans\u2010Retinoic acid as a differentiation therapy for acute promyelocytic leukemia: I. Clinical results","volume":"76","author":"Castaigne S","year":"1990","journal-title":"Blood"},{"key":"e_1_2_1_3_2","first-page":"1014","article-title":"Molecular remission in PML\/RAR \u03b1\u2010positive acute promyelocytic leukemia by combined all\u2010trans\u2010retinoic acid and idarubicin (AIDA) therapy","volume":"90","author":"Mandelli F","year":"1997","journal-title":"Blood"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.4.1192"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401230"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.9.3354"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.5.1701"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.2.124"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.5.1497"},{"key":"e_1_2_1_10_2","first-page":"3053","article-title":"Arsenic induces apoptosis through a c\u2010Jun NH2\u2010terminal kinase\u2010dependent, p53\u2010independent pathway","volume":"59","author":"Huang C","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_1_11_2","first-page":"776","article-title":"Arsenic targets tubulins to induce apoptosis in myeloid leukemia cells","volume":"59","author":"Li YM","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.9.772"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199811053391901"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.01079.x"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0320(19971201)29:4<306::AID-CYTO7>3.0.CO;2-7"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.9.3980"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1995.tb05603.x"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19950201)75:3<821::AID-CNCR2820750312>3.0.CO;2-Z"},{"key":"e_1_2_1_19_2","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1002\/j.1460-2075.1992.tb05185.x","article-title":"Genomic variability and alternative splicing generate multiple PML\/RARA transcripts that encode aberrant PMl proteins and PML\/RARA isoforms in acute promyelocytic leukemia","volume":"11","author":"Pandolfi PP","year":"1992","journal-title":"EMBO J"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401426"},{"key":"e_1_2_1_21_2","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1182\/blood.V89.9.3487","article-title":"Delicious poison\u2014arsenic trioxide for the treatment of leukemia","volume":"89","author":"Kwong YL","year":"1997","journal-title":"Blood"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1990.tb00389.x"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19961215)78:12<2510::AID-CNCR10>3.0.CO;2-Z"},{"key":"e_1_2_1_24_2","first-page":"1583","article-title":"Therapy\u2010related acute myelomonocytic leukemia following successful treatment for acute promyelocytic leukemia","volume":"9","author":"Todisco E","year":"1995","journal-title":"Leukemia"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.1057","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.1057","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T13:29:58Z","timestamp":1700400598000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.1057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,3,22]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2001,4]]}},"alternative-id":["10.1002\/ajh.1057"],"URL":"https:\/\/doi.org\/10.1002\/ajh.1057","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,3,22]]}}}