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Acute Non-Lymphocytic Leukemias

Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

Leukemia volume 20, pages 35–41 (2006)Cite this article

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-RARα 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.

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Acknowledgements

This work was supported by the Programme Hospitalier de Recherche Clinique (CHU Lille), the Association de Recherche contre le Cancer and the Ligue Nationale contre le Cancer (Comité du Nord).

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Author notes

  1. S de Botton and M A Sanz: These authors contributed equally to this work.

Authors and Affiliations

  1. The European APL Group, France

    S de Botton, S Chevret, H Dombret, X Thomas, C Recher, L Ades, B Quesnel, P Brault, M Fey, H Wandt, D Machover, A Guerci, F Maloisel, A M Stoppa, C Chomienne, L Degos & P Fenaux

  2. PETHEMA Group, Spain

    M A Sanz, G Martin, J D Mediavilla, C Rayon & J M Ribera

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  1. S de Botton
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  2. M A Sanz
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  3. S Chevret
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  4. H Dombret
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  5. G Martin
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  6. X Thomas
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  7. J D Mediavilla
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  9. L Ades
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Corresponding author

Correspondence to P Fenaux.

Additional information

Complete list of participants and addresses are given in appendix A.

Appendix A

Appendix A

The following clinical departments and personnel participated in the PETHEMA 96 trial:

Hospital Universitario La Fe, Valencia, Sanz MA, Martín G; Hospital Central de Asturias, Oviedo, Rayón C; Hospital Clínico San Carlos, Madrid, Díaz-Mediavilla J; Hospital Clínico Universitario, Valencia, Terol MJ; Hospital Insular de Las Palmas, Las Palmas, González JD; Hospital Clinic, Barcelona, Esteve J; Hospital General, Alicante, Rivas C; Hospital U. Germans Trias i Pujol, Badalona, Ribera JM; Complexo Hospitalario Xeral-Calde, Lugo, Arias J; Hospital Universitario, Salamanca, González M; Hospital de Cruces, Baracaldo, Alvarez MC; Complejo Hospitalario, León, Ramos F; Hospital Juan Canalejo, La Coruña, Debén G; Hospitales Ntra Sra del Pino/Sabinal, Las Palmas, Mataix R; Hospital Reina Sofia, Córdoba, Tabares S; Hospital Clínico Universitario, Valladolid, Fernández F; Hospital Universitario Vall D'Hebron, Barcelona, Bueno J; Hospital Son Dureta, Palma de Mallorca, Novo A; Hospital Xeral de Galicia, Santiago de Compostela, Pérez M; Hospital Ramón y Cajal, Madrid, Odriozola J; Hospital do Meixoeiro, Vigo, Loureiro C; Hospital Severo Ochoa, Leganés, Sánchez P; Hospital Dr Peset, Valencia, Sayas MJ; Hospital 12 de Octubre, Madrid, De la Serna J; Hospital General de Murcia, Murcia, Moraleda JM; H Universitario Virgen de la Victoria, Málaga, Pérez I; HU Puerta del Mar, Cádiz, Capote FJ Hospital San Pedro de Alcántara, Cáceres, Bergua JM; Hospital Materno-Infantil de Las Palmas, Las Palmas, Lodos JC Basurtuko Ospitalea, Basurto, Beltrán de Heredia JM; Hospital Rio Hortega, Valladolid, Peñarrubia MJ; Hospital Clínico Universitario Lozano Blesa, Zaragoza, Palomera L; Hospital General Jerez de la Frontera, Jerez de la Frontera, León A; Hospital General, Albacete, Romero JR; Hospital Xeral Cíes, Vitoria, Poderós C; Hospital Txagorritxu, Vitoria, Guinea JM; Hospital San Pau, Barcelona, Brunet S; Hospital General (Oncología Pediátrica), Alicante, Esquembre C; Hospital Rio Carrión, Palencia, Ortega F; Hospital U Marqués de Valdecilla, Santander, Conde E; H Universitario La Fe (Hospital Infantil), Valencia, Castell V

The following laboratories and personnel participated in the PETHEMA 96 trial:

Hospital Universitario La Fe, Valencia, Bolufer P, Barragán E; Hospital Universitario, Salamanca, González M, Chillón C; Hospital Clinic, Barcelona, Colomer D; Hospitales Ntra Sra del Pino/Sabinal, Las Palmas, Gómez T; Hospital Reina Sofia, Córdoba, Román J; Universidad de Navarra, Pamplona, Calasanz MJ; Hospital 12 de Octubre, Madrid, Bornstein R; Hospital Clínico San Carlos, Madrid, Villegas A; Hospital Clínico Universitario, Valencia, Marugán I; Hospital Ramón y Cajal, Madrid, Ferro C; Hospital do Meixoeiro, Vigo, Loureiro C; Hospital U Marqués de Valdecilla, Santander, Richard C.

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 biostatiscians. The following clinical departments participated in APL91 and APL93 trials:

French APL Group: S Castaigne, H Dombret (Paris), R Zittoun (Paris), E Archimbaud (Lyon), P Travade (Clermont Ferrand), C Gardin (Clichy), A Guerci (Nancy), S de Botton (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 Veil (Paris), T Lamy (Rennes), M Hayat (Villejuif), E Deconinck (Besancon), 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), E Wandt (Nurnberg), A Breitenbach (Stuttgart), B Brennscheidt (Freiburg), D Herrmann (Ulm), H Soucek (Dresden), H Strobel (Erlangen).

Swiss Group for Clinical Cancer Research AML group: K Geiser (Berne), M Fey (Berne), T Egger (Berne), E Jacky.

Belgian Group: JL Michaux (Bruxelles), A Bosly (Yvoir), E Meeus (Anvers), A Boulet (Mons).

Dutch group: P Daenen (Groningen), P Muus (Nijmegen).

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de Botton, S., Sanz, M., Chevret, S. et al. Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Leukemia 20, 35–41 (2006). https://doi.org/10.1038/sj.leu.2404006

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