The incidence of secondary leukemias

Background and Objectives. The term secondary leukemia is usually employed to indicate both forms of acute myeloid leukemia (AML) evolving from previo us myelodysplasia and forms of acute leukemia developing after exposure to environmental or therapeutic toxins or radiation (therapy-related). Seconda ry leukemias account for 10-30% of all AML. The majority of secondary Leuke mias resulting from the use of cytotoxic drugs can be divided into two well defined groups depending on whether the patient has received 1) alkylating agents or 2) drugs binding to the enzyme DNA-topoisomerase II. Alkylating agents related leukemias are very similar to post MDS leukemias being chara cterized frequently by a preleukemic phase, trilineage dysplasia, frequent cytogenetic abnormalities involving chromosomes 5 and 7 and a poor prognosi s. Secondary leukemias related to therapy with topoisomerase II inhibitors are not preceded by a preleukemic phase and show frequently balanced transl ocations involving chromosome 11q23. Among therapy-related leukemias, AML i s generally a second neoplasm, thus a predisposition to malignancy, indepen dently from previous chemotherapy, cannot be excluded. This review article examines the incidence of all secondary AMLs and the risk of therapy-relate d leukemia in relation to the different primary malignancies and treatments . Information Sources. The authors have been working in this field, both expe rimentally and at clinical level, contributing original papers for many yea rs. In addition, the material examined in this review includes articles pub lished in journals covered by MedLine, reviews in journals with high impact factor and recent reports presented at the Secondary Leukemia. An Update S ymposium held in Rome in November 1998. State of Art and Perspectives. The incidence of secondary leukemias is incr easing because of aging of the population (MDS is more frequent in elderly people) and widespread and successful use of chemoradiotherapy in cancer pa tients. In the GIMEMA archive of adult acute leukemia (2,964 AML pts from J une 1992 to June 1996) an antecedent hematologic disorder (AHD) and/or MDS was found in 8% of all patients (10% of 2,118 patients aged more than 45 ye ars and in 4% of 848 patients aged less than 45). In this series of patient s, 6% of all myeloid leukemias were therapy-related leukemia. Therapy-relat ed leukemias are a major problem in patients treated for Hodgkin's disease, non-Hodgkin's lymphoma, myeloma, polycythemia, breast cancer, ovarian carc inoma, or testicular carcinoma. In the GIMEMA archive more than 50% of pati ents with secondary AML have breast cancer, NHL, or HD. Alkylating agents, nitrosureas and procarbazine appear to have the highest leukemogenic potent ial. Furthermore aggressive chemotherapy and radiotherapy followed or not b y hematopoietic stem cell infusion will produce a more and more prolonged s urvival but also a greater incidence of secondary AML. Assessment of the ri sk of secondary leukemia should become part of any therapeutic plan for can cer patients. Avoidance of drugs with more leukemogenic potential will prod uce a marked reduction of secondary AML. (C)1999, Ferrata Storti Foundation .