title: Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention.
abstract: To determine prognosis of acute promyelocytic leukemia (APL) failing to front-line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of 52 patients (32 M/20 F; age: 37, 3-72) included in PETHEMA trials LPA96 and LPA99 who presented with either molecular failure (MOLrel, n=16) or hematological relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high-dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients with MOLrel (88%) achieved second molecular complete response (molCR), whereas 81% HEMrel patients responded to second-line treatment, with 58% molCR. After median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively, experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel, with longer survival (5-year survival: 64+/-14 vs 24+/-8%, P=0.01) and lower relapse risk (5-year relapse risk: 30+/-13 vs 64+/-9%; P=0.044). Additionally, age <or=40 and male gender were favorable variables for survival, whereas molecular response predicted longer leukemia-free survival. In conclusion, early institution of salvage therapy at molecular failure, before onset of hematological relapse, is beneficial in APL. Moreover, given the poor outcome of HEMrel managed with ATRA and HDAC, use of alternative therapeutic strategies in this setting is warranted.
authors.affiliation: Hospital Clínic, Barcelona, Spain. jesteve@clinic.ub.es
authors.forename: J
authors.initials: J
authors.lastname: Esteve
authors.forename: L
authors.initials: L
authors.lastname: Escoda
authors.forename: G
authors.initials: G
authors.lastname: Martín
authors.forename: V
authors.initials: V
authors.lastname: Rubio
authors.forename: J
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.forename: M
authors.initials: M
authors.lastname: González
authors.forename: C
authors.initials: C
authors.lastname: Rivas
authors.forename: C
authors.initials: C
authors.lastname: Alvarez
authors.forename: J D
authors.initials: JD
authors.lastname: González San Miguel
authors.forename: S
authors.initials: S
authors.lastname: Brunet
authors.forename: J F
authors.initials: JF
authors.lastname: Tomás
authors.forename: M
authors.initials: M
authors.lastname: Tormo
authors.forename: M J
authors.initials: MJ
authors.lastname: Sayas
authors.forename: P
authors.initials: P
authors.lastname: Sánchez Godoy
authors.forename: D
authors.initials: D
authors.lastname: Colomer
authors.forename: P
authors.initials: P
authors.lastname: Bolufer
authors.forename: M A
authors.initials: MA
authors.lastname: Sanz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000097:blood; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D008081:Liposomes; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D003561:Cytarabine; D014212:Tretinoin; D005047:Etoposide; D008942:Mitoxantrone; D015255:Idarubicin