Chemotherapy of secondary leukemias.

Chemotherapy of secondary leukemias is currently still considered to be associated with poor results. However, recent data suggest that the response to remission induction may substantially differ according to the previous medical history of the patients. Therapy related leukemia, arising following exposure to previous alkylating agents or radiotherapy, is often associated with chromosomal abnormalities involving chromosomes 5 and 7 and has a particularly bad response, whereas AML after exposure to epipodophyllotoxins or topoisomerase-II active agents could have a somewhat better response. Acute promyelocytic leukemia secondary to treatment of a primary malignant neoplasm seems to be associated with a better response if compared to other cytotypes of AML or to AML arising after transformation of myelodysplasia. However, here the literature data are not in full agreement, as different kinds of approaches have been applied. In fact, even if the problems encountered in treating patients with secondary leukemia are similar to those seen in patients with AML arising in a background of myelodysplasia (resistant disease and prolonged cytopenia after treatment), there are data suggesting that the use of high dose ara-C, with or without fludarabine, can circumvent resistance in a small but significant number of cases. One of the unsolved problems which still remains is how to consolidate the CR induced with high dose ara-C or with cycles based on anthracycline derivatives. In addition, another question relates to the categories of patients in whom chemotherapy may change the expected survival. Intensive post-remission chemotherapy, with or without autologous HSCT, may constitute an appropriate alternative for patients lacking a suitable sibling donor or for older patients who are in remission after chemotherapy and also able to tolerate other cycles of intensive chemotherapy. In this respect, the specific cytogenetic abnormality involved should be considered the most important prognostic factor for response and disease free survival; patients with abnormalities of chromosome 5 and 7 have a particularly low possibility of response and duration of CR. Furthermore, it is still debatable whether patients, especially the elderly, with these characteristics should go through a series of conventional treatments or just receive supportive treatment. On the other hand, patients with better prognostic factors should be entitled to further intensive treatments, taking into account possible delayed recovery and/or possible less successful collection of peripheral or marrow stem cells.