Early reappearance of primary solid cancer in patients treated with purine analogs

Two patients, observed at our institution, developed, after treatment with fludarabine, an early reappearance of metastatic primary solid cancers which were previously in long-lasting, complete remission. Patients had earlier suffered from a solid cancer considered cured and, subsequently, developed a lymphoid disorder treated with fludarabine. The two patients developed histologically confirmed hepatic metastasis from breast cancer and colic adenocarcinoma respectively 11 and 4 months after the beginning of fludarabine-therapy. Purine analogs have been reported to be effective against chronic lymphocytic leukemia and indolent lymphomas. However, these drugs induce severe immunodeficiency. In addition to the infectious diseases related to the treatment, the use of these drugs could facilitate the development of secondary neoplasms, related to the patient's impaired immunosurveillance. The surprisingly short latency between the therapy and the reappearance of non hematological cancers seen in our patients suggests that treatment with purine analogs may be involved in the reappearance of the tumors. In this regard, we suggest a possible role for purine analog-induced immunodeficiency in allowing the growth of previously undetected cancer cells rather than a direct drug-related mutagenic activity.