Therapy-Related Myeloid Neoplasms in Patients With Acute Promyelocytic Leukemia Treated With All-Trans-Retinoic Acid and Anthracycline-Based Chemotherapy

• Published in: Journal of clinical oncology Vol. 28; no. 24; pp. 3872 - 3879
• Main Authors: MONTESINOS, Pau, GONZALEZ, José D, DEBEN, Guillermo, SAYAS, María J, DE LA SERNA, Javier, RIBERA, Josep M, BUENO, Javier, MILONE, Gustavo, RIVAS, Concha, BRUNET, Salut, LÖWENBERG, Bob, SANZ, Miguel, GONZALEZ, José, RAYON, Chelo, DE LISA, Elena, AMIGO, Maria L, OSSENKOPPELE, Gert J, PENARRUBIA, María J, PEREZ-ENCINAS, Manuel, BERGUA, Juan
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.08.2010
• Subjects: Adult; Aged; Anthracyclines - administration & dosage; Anthracyclines - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Bone Marrow Neoplasms - chemically induced; Bone Marrow Neoplasms - epidemiology; Female; Hematologic and hematopoietic diseases; Humans; Incidence; Leukemia, Promyelocytic, Acute - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Neoplasms, Second Primary - chemically induced; Neoplasms, Second Primary - epidemiology; Prognosis; Prospective Studies; Risk Factors; Treatment Outcome; Tretinoin - administration & dosage; Tretinoin - adverse effects; Tumors; Antineoplastic agent; Human; Promyelocytic leukemia; Acute; Retinoid; Malignant hemopathy; Myeloproliferative syndrome; Chemotherapy; Cancerology; Treatment; Anthracyclins; Myeloid neoplasm; Cancer; M3 acute myelocytic leukemia; Tretinoin
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2010.29.2268

We analyzed the incidence, risk factors, and outcome of therapy-related myeloid neoplasms (t-MNs) in patients with acute promyelocytic leukemia (APL) in first complete remission (CR). From 1996 to 2008, 1,025 patients with APL were enrolled onto three sequential trials (LPA96, LPA99, and LPA2005) of the Programa Español para el Tratamiento de Enfermedades Hematológicas and received induction and consolidation therapy with all-trans-retinoic acid (ATRA) and anthracycline-based chemotherapy. Seventeen of 918 patients who achieved CR developed t-MN (10 with < 20% and seven with > or = 20% of bone marrow blasts) after a median of 43 months from CR. Partial and complete deletions of chromosomes 5 and 7 (nine patients) and 11q23 rearrangements (three patients) were the most common cytogenetic abnormalities. Overall, the 6-year cumulative incidence of t-MN was 2.2%, whereas in low-, intermediate-, and high-risk patients, the 6-year incidence was 5.2%, 2.1%, and 0%, respectively. Multivariate analysis identified age more than 35 years and lower relapse risk score as independent prognostic factors for t-MN. The median overall survival time after t-MN was 10 months. t-MN is a relatively infrequent, long-term, and severe complication after first-line treatment for APL with ATRA and anthracycline-based regimens. Therapeutic strategies to reduce the incidence of t-MN are warranted.