Aggressive growth of epithelial carcinomas following treatment with nucleoside analogues

Two patients, one with B-cell chronic lymphocytic leukemia (CLL) and one with hairy-cell leukemia (HCL), were treated with immunosuppressive chemotherapy. The patient with CLL was a 54-year-old female, who had had a squamous cell carcinoma (SCC) excised from her forehead 5 months before receiving the first course of fludarabine. During the fludarabine treatment, the patient developed a local SCC relapse and metastases in the neck. The carcinoma was treated by excision and radiotherapy, and further fludarabine treatment was withheld. Nevertheless, the SCC metastasized aggressively and the patient died 3 months after the start of fludarabine treatment, primarily due to respiratory failure. The autopsy revealed heavy SCC infiltrations involving the lungs, pleura, mediastinum, pericardium, and liver. The patient with HCL was a 69-year-old male. At the time of diagnosis of HCL, the patient had two solid tumors in the liver containing poorly differentiated epithelial carcinoma cells of unknown origin. During treatment with 2-chlorodeoxyadenosine (2CdA), the tumors in the liver rapidly spread in multiple intrahepatic metastases, followed by liver failure and death within 1 month. Fludarabine and 2CdA cause a substantial suppression of all lymphocyte subsets, in particular the T-cell line. T-lymphocytes are believed to be responsible for the usually slow growth and the low metastatic rate of the SCC skin lesions. It is therefore assumed that fludarabine and 2CdA in these two cases triggered an exacerbation of both tumors due to the T-cell depletion.