title: Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome.
abstract: A risk-adapted strategy based on all-trans retinoic acid (ATRA) and anthracycline monochemotherapy (PETHEMA LPA99 trial) has demonstrated a high antileukemic efficacy in acute promyelocytic leukemia. We designed a new trial (LPA2005) with the objective of achieving stepwise improvements in outcome. Between July 2005 and April 2009, low- and intermediate-risk patients (leukocytes < 10 x 10(9)/L) received a reduced dose of mitoxantrone for the second consolidation course, whereas high- risk patients younger than 60 years of age received cytarabine combined with ATRA and idarubicin in the first and third consolidation courses. Of 372 patients attaining complete remission after ATRA plus idarubicin (92.5%), 368 proceeded to consolidation therapy. For low- and intermediate-risk patients, duration of neutropenia and thrombocytopenia and hospital stay were significantly reduced without sacrificing antileukemic efficacy, compared with the previous LPA99 trial. For high-risk patients, the 3-year relapse rate was significantly lower in the LPA2005 trial (11%) than in the LPA99 (26%; P = .03). Overall disease-free survival was also better in the LPA2005 trial (P = .04). In conclusion, the lower dose of mitoxantrone resulted in a significant reduction of toxicity and hospital stay while maintaining the antileukemic activity, and the combination of ATRA, idarubicin, and cytarabine for high-risk acute promyelocytic leukemia significantly reduced the relapse rate in this setting. Registered at http://www.clinicaltrials.gov as NCT00408278.
authors.affiliation: Hospital Universitario La Fe, Valencia, Spain. msanz@uv.es
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.forename: Chelo
authors.initials: C
authors.lastname: Rayón
authors.forename: Alexandra
authors.initials: A
authors.lastname: Holowiecka
authors.forename: Javier
authors.initials: J
authors.lastname: de la Serna
authors.forename: Gustavo
authors.initials: G
authors.lastname: Milone
authors.forename: Elena
authors.initials: E
authors.lastname: de Lisa
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Vicente
authors.initials: V
authors.lastname: Rubio
authors.forename: José M
authors.initials: JM
authors.lastname: Ribera
authors.forename: Concha
authors.initials: C
authors.lastname: Rivas
authors.forename: Isabel
authors.initials: I
authors.lastname: Krsnik
authors.forename: Juan
authors.initials: J
authors.lastname: Bergua
authors.forename: José
authors.initials: J
authors.lastname: González
authors.forename: Joaquín
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.forename: Rafael
authors.initials: R
authors.lastname: Rojas
authors.forename: Félix
authors.initials: F
authors.lastname: Manso
authors.forename: Gert
authors.initials: G
authors.lastname: Ossenkoppele
authors.forename: José D
authors.initials: JD
authors.lastname: González
authors.forename: Bob
authors.initials: B
authors.lastname: Lowenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D020379:Risk Adjustment; D012307:Risk Factors; D015996:Survival Rate; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D018943:Anthracyclines; D003561:Cytarabine; D014212:Tretinoin