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Therapy-Related Acute Promyelocytic Leukemia

From the Service des Maladies du Sang, Lille; Hématologie, Hôpital du Bocage, Dijon; Hématologie, CHU, Strasbourg; Hématologie, CHU, Lyon; Hématologie, Hôpital Victor Provo, Roubaix; Hématologie, CHU, Vandoeuvre; Médecine Interne, Hôpital de l’Archet, Nice; Hôpital Jean Minjoz, Besançon; Service Hématologie, CHU, Toulouse; Service Hématologie, Hôtel Dieu and Myosotis 3, Hôpital St Louis, Paris; Service Hématologie, Centre Henri Becquerel, Rouen; and Institut Paoli Calmette, Marseille, France; Hospital University La Fe, Valencia; Hospital Central Asturias, Oviedo; Hospital University, Salamanca; Hospital Ramon y Cazal, Madrid; Hospital Puerta del Mar, Cadiz; and Hospital Clinic, Barcelona, Spain.

Address reprint requests to P. Fenaux, MD, PhD, Service d’Hématologie Clinique, Hôpital Avicenne Paris 13 University, 93000 Bobigny, Paris, France; email: pierre.fenaux{at}avc.ap-hop-paris.fr.

Purpose: To analyze patient cases of therapy-related acute promyelocytic leukemia (tAPL), occurring after chemotherapy (CT), radiotherapy (RT) or both for a prior disorder, diagnosed during the last 20 years in three European countries.

Patients and Methods: The primary disorder and its treatment, interval from primary disorder to tAPL, characteristics of tAPL, and its outcome were analyzed in 106 patients.

Results: Eighty of the 106 cases of tAPL were diagnosed during the last 10 years, indicating an increasing incidence of tAPL. Primary disorders were predominantly breast carcinoma (60 patients), non-Hodgkin’s lymphoma (15 patients), and other solid tumors (25 patients). Thirty patients had received CT alone, 27 patients had received RT alone, and 49 patients had received both. CT included at least one alkylating agent in 68 patients and at least one topoisomerase II inhibitor in 61 patients, including anthracyclines (30 patients), mitoxantrone (28 patients), and epipodophyllotoxins (19 patients). Median interval from primary disorder to tAPL diagnosis was 25 months (range, 4 to 276 months). Characteristics of tAPL were generally similar to those of de novo APL. With treatment using anthracycline-cytarabine–based CT or all-trans-retinoic acid combined with CT, actuarial survival was 59% at 8 years.

Conclusion: tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II–targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.

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