Treatment of newly diagnosed acute promyelocytic leukemia (APL) by all transretinoic acid (ATRA) combined with chemotherapy: The European experience. European APL Group

• Published in: Leukemia & lymphoma Vol. 16; no. 5-6; p. 431
• Main Authors: Fenaux, P, Chastang, C, Chomienne, C, Castaigne, S, Sanz, M, Link, H, Löwenberg, B, Fey, M, Archim-Baud, E, Degos, L
• Format: Journal Article
• Language: English
• Published: United States 01.02.1995
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bone Marrow Transplantation; Cell Differentiation - drug effects; China; Combined Modality Therapy; Cytarabine - administration & dosage; Daunorubicin - administration & dosage; Disease-Free Survival; Etoposide - administration & dosage; Europe; Humans; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Leukemia, Promyelocytic, Acute - drug therapy; Leukemia, Promyelocytic, Acute - mortality; Leukemia, Promyelocytic, Acute - therapy; Leukocytosis - chemically induced; Leukocytosis - mortality; Life Tables; Middle Aged; Mitoxantrone - administration & dosage; New York; Pilot Projects; Remission Induction; Survival Rate; Treatment Outcome; Tretinoin - adverse effects; Tretinoin - therapeutic use; New York; China; Europe
• ISSN: 1042-8194

All transretinoic acid (ATRA) gives complete remission (CR) rates of 80 to 90% in newly diagnosed acute promyelocytic leukemia (APL). However, it has two major drawbacks (1) a rapid rise in WBC in some patients, with potentially fatal ATRA syndrome (2) rapid relapse with maintenance therapy using ATRA alone or low dose chemotherapy. The French APL group therefore designed a treatment approach with ATRA followed by intensive chemotherapy. The latter was administered after CR achievement with ATRA, or was rapidly added to ATRA in case of rapid rise in leukocyte counts. This combined approach, in a pilot study and in a randomized trial, proved superior to intensive chemotherapy alone, by slightly increasing the CR rate but more importantly by reducing the relapse rate. These results were confirmed by the Chinese, Japanese and New York groups. Our group (and other European groups) are now testing in a new randomized trial the better timing of ATRA and chemotherapy administration (ATRA followed by chemotherapy or ATRA plus chemotherapy) and the role (after an intensive consolidation) of maintenance treatment with intermittent ATRA, continuous low dose chemotherapy or both.