title: Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy.
abstract: We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/ 806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26950/mm3 (7700-162000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age <45 years (P=0.05), bcr3 PML-RARalpha isoform (P= 0.0003) and high WBC counts (> or = 10,000/ mm3) (P<0.0001) as risk factors for EM relapse. In multivariate analysis, only high WBC count remained significant (P= 0.001). Patients with EM relapse had a poorer outcome since median survival from EM relapse was 6.7 months as compared to 26.3 months for isolated BM relapse (P=0.04). In conclusion, EM relapse in APL occurs more frequently in patients with increased WBC counts (> or = 10,000/mm3) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC > or = 10,000/mm3 at diagnosis remains to be established.
authors.affiliation: The European APL Group, France.
authors.forename: S
authors.initials: S
authors.lastname: de Botton
authors.forename: M A
authors.initials: MA
authors.lastname: Sanz
authors.forename: S
authors.initials: S
authors.lastname: Chevret
authors.forename: H
authors.initials: H
authors.lastname: Dombret
authors.forename: G
authors.initials: G
authors.lastname: Martin
authors.forename: X
authors.initials: X
authors.lastname: Thomas
authors.forename: J D
authors.initials: JD
authors.lastname: Mediavilla
authors.forename: C
authors.initials: C
authors.lastname: Recher
authors.forename: L
authors.initials: L
authors.lastname: Ades
authors.forename: B
authors.initials: B
authors.lastname: Quesnel
authors.forename: P
authors.initials: P
authors.lastname: Brault
authors.forename: M
authors.initials: M
authors.lastname: Fey
authors.forename: H
authors.initials: H
authors.lastname: Wandt
authors.forename: D
authors.initials: D
authors.lastname: Machover
authors.forename: A
authors.initials: A
authors.lastname: Guerci
authors.forename: F
authors.initials: F
authors.lastname: Maloisel
authors.forename: A M
authors.initials: AM
authors.lastname: Stoppa
authors.forename: C
authors.initials: C
authors.lastname: Rayon
authors.forename: J M
authors.initials: JM
authors.lastname: Ribera
authors.forename: C
authors.initials: C
authors.lastname: Chomienne
authors.forename: L
authors.initials: L
authors.lastname: Degos
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis / Q000188:drug therapy*; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D014212:Tretinoin