Acute Myeloblastic Leukemia after Adjuvant Chemotherapy with Melphalan in Breast Cancer. Case Report with Cytogenetic Analysis

Therapy of solid and hematologic tumors with alkylating agents appears to increase the frequency of acute non-lymphocytic leukemia (ANLL), as indicated by the cases reported in the literature. The carcinogenetic mechanism of alkylating agents seems related to their ability to damage DNA, and this is supported by the findings of multiple cytogenetic abnormalities in these patients. We report a case of ANLL secondary to therapy with melphalan, which was utilized on an adjuvant basis for breast cancer. ANLL developed 24 months after chemotherapy was discontinued. Results of the cytogenetic analysis in our patient showed multiple rearrangements and marker chromosomes. Among these was a large metacentric chromosome, identified in 6 of 8 karyotypes, in the size range of group A, which probably resulted from a translocation t(7;14) (7qter→7p11::14p11-→14qter). The natural history of the underlying disease and of the ANLL in our patient and data from chromosomal analysis seem to confirm the hypothesis that alkylating agents are potentially leukemogenic in man, probably through genetic damage. This possibility should be considered when such cytotoxic drugs are used in an adjuvant setting.