1. ¹The European APL Group, France
2. ²PETHEMA Group, Spain

Correspondence: Professor P Fenaux, Service d'Hématologie Clinique, Hôpital Avicenne/Université Paris XIII, 125 route de Stalingrad, 93009 Bobigny, France. E-mail: pierre.fenaux@avc.ap-hop-paris.fr

³These authors contributed equally to this work.

Received 16 May 2005; Revised 23 August 2005; Accepted 12 September 2005; Published online 24 November 2005.

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 26 950/mm³ (7700–162 000). 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-RAR isoform (P=0.0003) and high WBC counts (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 (10 000/mm³) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC 10 000/mm³ at diagnosis remains to be established.