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 treat-ment, 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 usu-ally 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.

J Clin Oncol 21: 2123-2137.© 2003 by American Society of Clinical Oncology.

THERAPY-RELATED MYELODYSPLASTIC syndromes (tMDS) and acute myeloid leukemia (tAML) have been increasingly described during the last 30 years after neoplastic (or less often nonneoplastic) disorders treated by chemotherapy (and radiotherapy to a lesser extent). 1 Until the early 1980s, most illnesses developed 3 to 10 years after prolonged use of alkylating agents, and presented as tMDS with complete or partial deletion of chromosome 7 or 5, often with other cytogenetic abnormalities (classic tMDS-tAML). 2 More recently, tAML has been described after the use of topoisomerase II inhibitors (epipodophyllotoxins such as etoposide [VP16] or teniposide [VM26], and anthracycline or anthracene dione). These illnesses often developed early (12 to 36 months) after onset of chemotherapy, usually had no preleukemic phase, and showed normal karyotype or cytogenetic rearrangements specific to de novo AML. 2 In the latter, 11q23 rearrangements predominated, whereas t (8; 21), inv (16), and t (15; 17) were less often seen, and other rearrangements were rarely observed. 1, 3 tMDS and tAML have also been reported after autologous stem-cell transplantation. 4 In addition, prolonged use of hydroxyurea in myeloproliferative disorders might increase the patients’ risk of progression to AML. 5