Therapy‐related leukemia following chemoradiotherapy for esophageal cancer

Abstract

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.

Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States, 1975-2008

“…We report newly emerging tAML risks coincident with the expanding use of chemotherapy for cancers of the esophagus, anus, cervix, endometrium, and prostate, which have been suggested previously in case reports. [36][37][38] For esophageal, anal, cervical, and endometrial cancers, the emerging tAML risks could be related to the addition of platinumbased regimens to standard treatment approaches for certain patients, [39][40][41] whereas for prostate cancer, risks may be associated with an increasing role of chemotherapy in the (neo)adjuvant setting and for the treatment of castration-resistant disease. 42 We also observed an increased risk for tAML after bone and joint cancers since the 1990s, which may be associated with the addition of ifosfamide and etoposide to standard chemotherapy.…”

Long-term Follow-up of a Randomized Phase II Study of Cisplatin/5-FU Concurrent Chemoradiotherapy for Esophageal Cancer (KROSG0101/JROSG021)

“…As a serious late toxicity, secondary malignancies possibly related to cancer treatment were noted in three patients. Although there are several case reports on therapy-related leukemia following definitive CRT for esophageal cancer (19,20), therapy-related solid tumors following CRT for esophageal cancer have not been reported. Acute myelogenous leukemia was noted 77 months after CRT, follicular lymphoma of the duodenum 53 months after CRT and lung squamous cell carcinoma 96 months after CRT.…”

Therapy-Related Acute Myeloid Leukemia 2 Months after Chemoradiotherapy for Esophageal Cancer: A Case Report

“…The acute and late adverse events for chemoradiotherapy have been previously reported [3,6]; however, the reports on therapy-related AML after chemoradiotherapy for esophageal cancer are limited with only one report describing four patients with therapyrelated AML after chemoradiotherapy for esophageal cancer. Overt AML from myelodysplastic syndrome was reported in two of four patients, and its onset after chemoradiotherapy was 19-41 months [7]. Herein, we report a patient with therapy-related AML 2 months after chemoradiotherapy for esophageal cancer.…”