title: Have all-trans retinoic acid and arsenic trioxide replaced all-trans retinoic acid and anthracyclines in APL as standard of care.
abstract: Until recently, the standard of care in the treatment of APL has involved the combination of all-trans retinoic acid with anthracycline-based chemotherapy during both induction and consolidation. Additionally, the intensity of consolidation chemotherapy has evolved according to a universally accepted relapse-risk stratification algorithm based on the white cell and platelet counts at presentation. That standard of care is being challenged by the increasing incorporation of arsenic trioxide into front-line treatment protocols, based on two complementary observations. The first is the undoubted anti-leukaemic activity of arsenic trioxide as shown in the relapsed and refractory setting, and in the initial management of low- and intermediate-risk patients. The second is an improved understanding of the action of both all-trans retinoic acid and arsenic trioxide in mediating APL cell eradication, with increasing recognition that PML-RARA fusion protein degradation rather than direct induction of terminal differentiation is the primary mechanism for their ability to eliminate leukaemia initiating cells. As a result, we believe the standard of care for initial therapy in APL is shifting towards an all-trans retinoic acid plus arsenic trioxide-based approach, with additional chemotherapy reserved for patients with high-risk disease.
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia; University of Sydney, Sydney, NSW 2006, Australia. Electronic address: harry@email.cs.nsw.gov.au.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Iland
authors.affiliation: Department of Haematology, The Alfred Hospital, Commercial Road, Melbourne, VIC 3004, Australia; Monash University, Melbourne, VIC, Australia. Electronic address: andrew.wei@monash.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wei
authors.affiliation: Peter MacCallum Cancer Centre, 7, St. Andrews Place, East Melbourne, VIC 3002, Australia; University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address: john.seymour@petermac.org.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D015255:Idarubicin / Q000008:administration & dosage; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000628:therapy; D060046:Maintenance Chemotherapy; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D015337:Multicenter Studies as Topic; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017713:Platelet Transfusion; D017410:Practice Guidelines as Topic; D012074:Remission Induction; D018570:Risk Assessment; D013866:Thioguanine; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D001152:Arsenicals; D001779:Blood Coagulation Factors; D010087:Oxides; D003561:Cytarabine; D014212:Tretinoin; D005047:Etoposide; D008942:Mitoxantrone; D013866:Thioguanine; D000077237:Arsenic Trioxide; D006918:Hydroxyurea; D015255:Idarubicin
keywords: PML-RARA degradation; all-trans retinoic acid; arsenic trioxide; relapse