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Article: Arsenic trioxide- and idarubicin-induced remissions in relapsed acute promyelocytic leukaemia: Clinicopathological and molecular features of a pilot study

TitleArsenic trioxide- and idarubicin-induced remissions in relapsed acute promyelocytic leukaemia: Clinicopathological and molecular features of a pilot study
Authors
Issue Date2001
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35105
Citation
American Journal Of Hematology, 2001, v. 66 n. 4, p. 274-279 How to Cite?
AbstractArsenic trioxide (As2O3) effectively induces remissions in relapsed acute promyelocytic leukaemia (APL), but the safety of its long-term 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 As2O3 followed by consolidation with idarubicin in the treatment of APL in relapse. Eight patients were treated with As2O3 at a daily dose of 10 mg until remission, followed by three monthly courses of idarubicin, at 6 mg/m2/day for 5 days in the first course and 6 mg/m2/day for 2 days in the subsequent two courses. All patients achieved morphological but not molecular remission after As2O3 treatment. During As2O3 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-G1 cell fraction on DNA histogram as markers, showed induction of apoptosis of APL cells in vivo. With both qualitative and real-time 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-positive after being transiently negative. One patient died from an intracranial extramedullary relapse after achieving marrow molecular remission. We conclude that As2O3 induction followed by idarubicin consolidation is an effective therapy for APL in relapse. This regimen avoids the possible long-term toxicities of As2O3 and mutagenicity of combination chemotherapy, a strategy that might be suitable for this potentially curable leukaemia. © 2001 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/162503
ISSN
2015 Impact Factor: 5.0
2015 SCImago Journal Rankings: 1.761
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKwong, YLen_US
dc.contributor.authorAu, WYen_US
dc.contributor.authorChim, CSen_US
dc.contributor.authorPang, Aen_US
dc.contributor.authorSuen, Cen_US
dc.contributor.authorLiang, Ren_US
dc.date.accessioned2012-09-05T05:20:35Z-
dc.date.available2012-09-05T05:20:35Z-
dc.date.issued2001en_US
dc.identifier.citationAmerican Journal Of Hematology, 2001, v. 66 n. 4, p. 274-279en_US
dc.identifier.issn0361-8609en_US
dc.identifier.urihttp://hdl.handle.net/10722/162503-
dc.description.abstractArsenic trioxide (As2O3) effectively induces remissions in relapsed acute promyelocytic leukaemia (APL), but the safety of its long-term 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 As2O3 followed by consolidation with idarubicin in the treatment of APL in relapse. Eight patients were treated with As2O3 at a daily dose of 10 mg until remission, followed by three monthly courses of idarubicin, at 6 mg/m2/day for 5 days in the first course and 6 mg/m2/day for 2 days in the subsequent two courses. All patients achieved morphological but not molecular remission after As2O3 treatment. During As2O3 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-G1 cell fraction on DNA histogram as markers, showed induction of apoptosis of APL cells in vivo. With both qualitative and real-time 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-positive after being transiently negative. One patient died from an intracranial extramedullary relapse after achieving marrow molecular remission. We conclude that As2O3 induction followed by idarubicin consolidation is an effective therapy for APL in relapse. This regimen avoids the possible long-term toxicities of As2O3 and mutagenicity of combination chemotherapy, a strategy that might be suitable for this potentially curable leukaemia. © 2001 Wiley-Liss, Inc.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35105en_US
dc.relation.ispartofAmerican Journal of Hematologyen_US
dc.rightsAmerican Journal of Hematology. Copyright © John Wiley & Sons, Inc.-
dc.subject.meshAdulten_US
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols - Pharmacology - Therapeutic Useen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshArsenicals - Administration & Dosage - Pharmacologyen_US
dc.subject.meshDrug Evaluationen_US
dc.subject.meshDrug Synergismen_US
dc.subject.meshFemaleen_US
dc.subject.meshFollow-Up Studiesen_US
dc.subject.meshHumansen_US
dc.subject.meshIdarubicin - Administration & Dosage - Pharmacologyen_US
dc.subject.meshLeukemia, Promyelocytic, Acute - Blood - Drug Therapy - Genetics - Pathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshNeoplasm Proteins - Blooden_US
dc.subject.meshNeoplasm, Residualen_US
dc.subject.meshOncogene Proteins, Fusion - Blooden_US
dc.subject.meshOxides - Administration & Dosage - Pharmacologyen_US
dc.subject.meshPilot Projectsen_US
dc.subject.meshProspective Studiesen_US
dc.subject.meshRecurrenceen_US
dc.subject.meshRemission Inductionen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshSalvage Therapyen_US
dc.subject.meshTreatment Outcomeen_US
dc.subject.meshTumor Markers, Biological - Blooden_US
dc.titleArsenic trioxide- and idarubicin-induced remissions in relapsed acute promyelocytic leukaemia: Clinicopathological and molecular features of a pilot studyen_US
dc.typeArticleen_US
dc.identifier.emailKwong, YL:ylkwong@hku.hken_US
dc.identifier.emailChim, CS:jcschim@hku.hken_US
dc.identifier.emailLiang, R:rliang@hku.hken_US
dc.identifier.authorityKwong, YL=rp00358en_US
dc.identifier.authorityChim, CS=rp00408en_US
dc.identifier.authorityLiang, R=rp00345en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/ajh.1057en_US
dc.identifier.pmid11279639-
dc.identifier.scopuseid_2-s2.0-0035095714en_US
dc.identifier.hkuros59695-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035095714&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume66en_US
dc.identifier.issue4en_US
dc.identifier.spage274en_US
dc.identifier.epage279en_US
dc.identifier.isiWOS:000167405100008-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridKwong, YL=7102818954en_US
dc.identifier.scopusauthoridAu, WY=7202383089en_US
dc.identifier.scopusauthoridChim, CS=7004597253en_US
dc.identifier.scopusauthoridPang, A=7007044165en_US
dc.identifier.scopusauthoridSuen, C=7102317262en_US
dc.identifier.scopusauthoridLiang, R=26643224900en_US

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