Secondary acute myeloid leukemia in children previously treated with alkylating agents, intercalating topoisomerase II inhibitors, and irradiation.

PURPOSE: Patient records were reviewed to identify cases of secondary acute myeloid leukemia (AML) with clinical and cytogenetic features characteristic of classic epipodophyllotoxin-related AML in patients whose prior treatment for cancer did not include these agents. PATIENTS AND METHODS: Four cases of secondary AML with chromosomal abnormalities involving bands 11q23 and 21q22, in the absence of prior treatment with etoposide or teniposide, were identified among patients treated at St Jude Children's Research Hospital between January 1980 and April 1992.
RESULTS: The four identified patients were initially treated for rhabdomyosarcoma, non-Hodgkin's lymphoma (n = 2), and Hodgkins' disease. Prior chemotherapy included relatively low cumulative doses of doxorubicin (median, 150 mg/m2; range, 120 to 375 mg/m2) and cyclophosphamide (median, 3,100 mg/m2; range, 2,250 to 11,400 mg/m2). All four patients had received radiation therapy: 59.4 Gy to the right middle ear for rhabdomyosarcoma; 15 Gy and 12 Gy to the abdomen and right lower quadrant, respectively, for non-Hodgkin's lymphoma; 27 Gy to the right orbit for non-Hodgkin's lymphoma; and 36.6 Gy to the mantle-paraaortic-spleen regions plus 20.4 Gy inverted-Y radiation at relapse for Hodgkin's disease. Secondary AML was diagnosed a median of 38 months after initial diagnosis (range, 14 to 55). Leukemic cell translocations involved band 11q23 in two cases and band 21q22 in two. Although all patients obtained a complete remission (CR), only one remains disease-free (at 34 months), following an allogeneic bone marrow transplant.
CONCLUSION: Intercalating topoisomerase II inhibitors (doxorubicin, dactinomycin), when combined with alkylating agents and irradiation, may cause secondary AML.