New strategies for the treatment of acute promyelocytic leukaemia.
Acute promyelocytic leukaemia (APL) is a distinct entity of acute myeloid leukaemia characterized by blast cell morphology, severe coagulopathy and t(15;17) translocation that fuses the PML gene on chromosome 15 to the retinoic acid receptor alpha (RAR alpha) gene on chromosome 17. Past experience indicated that APL is highly sensitive to anthracycline-based chemotherapy. GIMEMA experience reported a similar complete remission (CR) rate (77% versus 69%) in APL patients treated with idarubicin alone or idarubicin plus Ara-C, respectively. At present all-trans-retinoic-acid (ATRA) represents the mainstay of APL treatment. Current available clinical trials show that combination of ATRA and anthracycline induction therapy produces approximately 90% CR rate and seems to significantly improve disease-free survival. Furthermore ATRA combined therapy reduces induction death rate since ATRA syndrome has been managed with high-dose corticosteroids. However the development of ATRA resistance could limit the use of ATRA as post-remission treatment and therefore future efforts should be addressed to the search of new retinoids with comparable clinical activity, which can overcome ATRA resistance.
Mandelli
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Dipartimento di Biotecnologie Cellulari ed Ematologia, Universita La Sapienza, Rome, Italy.
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D012074:Remission Induction; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D014212:Tretinoin; D015255:Idarubicin