Therapy-related leukemia following chemoradiotherapy for esophageal cancer

Chemoradiotherapy has improved the outcome of patients with esophageal cancer. Although a sufficiently long-time survival has resulted in the increase of several treatment-related late toxicities, little is still known about the incidence of secondary malignancies. In our hospital, 348 patients with esophageal cancer received chemotherapy consisting of nedaplatin and 5-fluorouracil and concurrent irradiation. Median and average follow-up durations were 8 and 21 months (1-92), respectively. Four patients developed leukemia after 19-48 months of follow-up. Two patients were diagnosed with overt leukemia from myelodysplastic syndrome presenting a complex karyotype, including the deletion of chromosome 5 or 7. Notably, one patient showed an additional chromosomal abnormality with t(9;22)(q34;q11). Other patients developed acute myeloid leukemia with t(9;22)(q34;q11) and Burkitt leukemia with t(8;14)(q24;q32). All patients eventually succumbed to leukemia. Platinum and fluorouracil have shown relatively lower risks for secondary malignancies in comparison with alkylating agents and topoisomerase II inhibitors. Especially, nedaplatin has never been described to introduce secondary neoplasms. Our report supports the idea that the concurrent administration of radiotherapy with these agents affects the risk of leukemia. Interestingly, rare balanced chromosomal abnormalities were observed in the present cases, thus providing new insights into the leukemogenesis of therapy-related leukemia.