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Therapy in APL

Long-term follow-up confirms the benefit of all-trans retinoic acid in acute promyelocytic leukemia

Leukemia volume 14, pages 1371–1377 (2000)Cite this article

Abstract

First results of a randomized trial (APL91 trial) and other randomized or non-randomized studies have shown that ATRA followed by chemotherapy significantly increased event-free survival (EFS) and survival, and decreased the incidence of relapse by comparison to chemotherapy alone in newly diagnosed APL. We present here long-term follow-up of the APL91 trial. In this trial, 101 patients had been randomized between ATRA followed by three courses of daunorubicin-AraC chemotherapy (ATRA group) and the same chemotherapy alone (chemotherapy group). Results were reanalyzed 73 months after closing of patient entry. Updated results of APL 91 trial found a Kaplan–Meier estimate of EFS and relapse rate at 4 years of 63% and 31% in the ATRA group, as compared to 17% and 78% in the chemotherapy group (P = 10−4 and relative risk 2.95, P = 10−4 and relative risk 3.68, respectively). Kaplan–Meier survival at 4 years was 76% in the ATRA group and 49% in the chemotherapy group (P = 0.026, relative risk 2.7). In the chemotherapy group, seven of the 27 relapses occurred after 18 months, but no relapse was seen after 43 months. In the ATRA group, four of the 17 relapses occurred after 18 months, including two late relapses (at 58 and 74 months). In the chemotherapy group, 23 of the 25 patients who relapsed achieved a second CR with ATRA, and the Kaplan–Meier estimate of second relapse was 40% at 30 months. In the ATRA group, the 10 patients who relapsed and were retreated with ATRA achieved a second CR. In conclusion, long-term results of APL91 trial confirm the superiority of the combination of ATRA and chemotherapy over chemotherapy alone in newly diagnosed APL, and that ATRA should be incorporated in the front-line treatment of APL.

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Acknowledgements

This work was supported by the Programme Hospitalier de Recherche Clinique, Centre Hospitalier Universitaire (CHU) of Lille, and the Association pour la Recherche contre le Cancer (ARC).

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  1. Service des Maladies du Sang, CHU, 1 place de Verdun, Lille, 59037, France

    P Fenaux

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for the European APL group

Appendix

Appendix

Dr P Fenaux and Dr L Degos served as cochairmen, and Dr C Chastang and S Chevret-Chastang (Department of Biostatistics, Hopital St Louis, Paris) as biostatisticians.

The following clinical departments participated in the APL93 trial.

French APL group

S Castaigne, H Dombret (Paris), R Zittoun (Paris), E Archimbaud (Lyon), P Travade (Clermont Ferrand), C Gardin (Clichy), A Guerci (Nancy), P Fenaux (Lille), AM Stoppa (Marseille), F Dreyfus (Paris), F Stamatoulas (Rouen), F Rigal-Huguet (Toulouse), H Guy (Dijon), JJ Sotto (Grenoble), F Maloisel (Strasbourg), J Reiffers (Pessac), A Gardembas (Angers), D Bordessoule (Limoges), N Fegueux (Montpellier), A Buzyn (Paris), T Lamy (Rennes), Ph Brault (Villejuif), E Deconinck (Besançon), E Guyotat (St Etienne), M Martin (Annecy), E Cony-Makhoul (Bordeaux), JP Abgrall (Brest), O Reman (Caen), B Desablens (Amiens), JL Harousseau (Nantes), Y Bastion (Lyon), JP Pollet (Valenciennes), J Pulik (Argenteuil), M Lepeu (Avignon), M Renoux (Bayonne), P Morel (Lens), P Henon (Mulhouse), N Gratecos (Nice), P Colombat (Tours), D Machover (Villejuif), A Dor (Antibes), P Casassus (Bobigny), J Donadio (Castelnou), B Salles (Chalon), B Legros (Clermont Ferrand), P Audhuy (Colmar), A Dutel (Compiègne), N Philippe (Lyon), B Benothman (Meaux), C Christian (Metz), C Margueritte (Montpellier), F Witz (Nancy), A Pesce (Nice), A Baruchel (Paris), L Sutton (Paris), C Quetin (Pointe à Pitre), B Pignon (Reims), E Vilmer (Paris), E Bourquard (St Brieuc), JP Marolleau (Paris), P Robert (Toulouse), B Despax (Toulouse), G Nedellec, P Auzanneau (Paris), M Janvier (St Cloud).

Spanish AML group

O Rayon (Oviedo), M Sanz (Valencia), J San Miguel (Salamanca), J Montagud (Valencia), E Condé (Santander), P Javier de la Serna (Madrid), G Martin (Valencia), M Perez Encinas (Santiago), JP Torres Carrete (Juan Canalejo), J Zuazu (Barcelone), J Odriozola (Madrid), E Gomez-Sanz (Madrid), L Palomera (Zaragoza), L Villegas (Almeria), A Deben (Juan Canalejo), P Besalduch (Palma de Mallorca).

Cooperative AML study group, Germany

H Link (Hannover), A Ganser (Frankfurt), H Wandt (Nurnberg), A Breitenbach (Stuttgart), B Brennscheidt (Freiburg), D Herrmann (Ulm), H Soucek (Dresden), H Strobel (Erlangen)

SAKK Swiss AML group

K Geiser (Berne), M Fey (Berne), T Egger (Berne), E Jacky

Belgian groups

JL Michaux (Bruxelles), A Bosly (Yvoir), E Meeus (Anvers), A Boulet (Mons), Ph Mineur (Gilly)

Dutch groups

P Daenen (Groningen), P Muus (Nijmegen)

British group

JA Whittaker (Cardiff)

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Fenaux, P., Chevret, S., Guerci, A. et al. Long-term follow-up confirms the benefit of all-trans retinoic acid in acute promyelocytic leukemia. Leukemia 14, 1371–1377 (2000). https://doi.org/10.1038/sj.leu.2401859

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