Therapy-related Leukemia and Myelodysplastic Syndrome: Clinical, Cytogenetic, and Prognostic Features

One hundred twelve patients who developed acute leukemia or a myelodysplastic syndrome (MDS) after chemotherapy or irradiation for another malignancy were reviewed. The median time from initial therapy to development of secondary leukemia or MDS was 71 months (range, 7 to 331 months). The initial malignancy was hematologic in 43%. An MDS presentation occurred in 57 patients (51%), 55% of whom subsequently transformed to acute leukemia. Chromosomal abnormalities were documented in marrow specimens from 70 of 89 patients with analyzable metaphases (79%; 69% of the total group). Compared with 34 patients with metachronous secondary leukemia without prior chemotherapy or irradiation, those with therapy-related leukemia exhibited a significantly higher frequency of abnormalities of chromosomes 5 and/or 7 (43% v 18%), and lower incidence of diploid karyotypes (18% v 50%). Chromosome 5 and/or 7 abnormalities were also significantly higher in patients previously treated with alkylating agents, procarbazine, and nitrosoureas (72% to 83%), compared with those who had received cyclophosphamide-based regimens (29%), other chemotherapies (14%), or irradiation alone (29%). The median overall survival from diagnosis of the secondary leukemia or MDS was 30 weeks. Survival was significantly shorter for patients with acute leukemia compared with MDS presentation (21 v 45 weeks); in the latter category, it was similar whether evolution to acute leukemia occurred or not. Of 72 patients treated with antileukemia therapy, 29% achieved complete remission (CR). A multivariate analysis of prognostic factors demonstrated the cytogenetic pattern to be the most important characteristic determining remission rate and survival. Other important prognostic features were the morphologic presentation (MDS v acute leukemia) for probability of achieving remission, and patient age and marrow blasts percentage for survival.