title: Therapy-related myelodysplastic syndrome-acute myelogenous leukemia in patients treated for acute promyelocytic leukemia: an emerging problem.
abstract: The use of all-trans retinoic acid (ATRA) in combination with chemotherapy has markedly improved the prognosis for patients with acute promyelocytic leukemia (APL); the higher complete remission (CR) and survival rates now reported in this disease almost approach those obtained for other highly curable hematologic malignancies. Of 77 patients with APL who were consecutively treated at a single institution and who achieved CR after induction and consolidation therapy, 5 (6.5%) acquired therapy-related myelodysplasia (tMDS), acute myelogenous leukemia (AML), or both (tMDS-AML). Of these, 3 of 46 (6.5%) patients received front-line chemotherapy with or without ATRA and acquired tMDS-AML while in first remission of APL. Two underwent repeated chemotherapy cycles with ATRA because of APL relapse and acquired tMDS-AML while in the second or third remission of APL. In 2 patients, clinical and biologic characteristics of tMDS-AML were as expected for postalkylating forms (long latency, MDS phase preceding AML, karyotypic aberrations involving chromosomes 5 or 7), even though one of them had not previously received alkylating drugs. Three of the 5 patients died shortly after tMDS-AML diagnosis, one is alive with tMDS, and one is alive and in CR after allogeneic bone marrow transplantation. The occurrence of tMDS-AML after successful therapy for APL is an emerging problem. The availability of prognostic score systems at initial diagnosis and monitoring of residual disease by polymerase chain reaction might allow better tailoring of treatment intensity in APL to spare unnecessary toxicity and to minimize the risk for tMDS-AML in patients who are presumably cured.
authors.affiliation: Department of Human Biotechnologies and Hematology, University La Sapienza of Rome, Cattedra di Ematologia, Via Benevento 6-00161, Rome, Italy. rob.lati@libero.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Petti
authors.forename: Susanna
authors.initials: S
authors.lastname: Fenu
authors.forename: Marco
authors.initials: M
authors.lastname: Mancini
authors.forename: Maria Antonietta Aloe
authors.initials: MA
authors.lastname: Spiriti
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Gregorio A
authors.initials: GA
authors.lastname: Brunetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Avvisati
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo Coco
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D020732:Cytogenetic Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D014212:Tretinoin