Aggressive growth of epithelial carcinomas following treatment with nucleoside analogues

Abstract

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 ®rst course of¯udarabine. During thē udarabine treatment, the patient developed a local SCC relapse and metastases in the neck. The carcinoma was treated by excision and radiotherapy, and further¯udarabine treatment was withheld. Nevertheless, the SCC metastasized aggressively and the patient died 3 months after the start of¯udarabine treatment, primarily due to respiratory failure. The autopsy revealed heavy SCC in®ltrations 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¯udarabine and 2CdA in these two cases triggered an exacerbation of both tumors due to the T-cell depletion.

Skin cancer after nonmyeloablative hematopoietic cell transplantation

“…Fludarabine depletes CD3 þ , CD4 þ , and CD8 þ lymphocytes over a period of many months. 39,40 Larsen et al 41 reported metastatic SCC in one patient following treatment with fludarabine and in another after 2-CdA. Davidovitz et al 42 reported a patient with a flare of scalp SCC following treatment with fludarabine.…”

Second cancers in patients with chronic lymphocytic leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: distribution and clinical outcomes

“…In one report, an aggressive course of squamous cell carcinoma (SCC) with diffuse metastasis was noted after treatment with fludarabine. [ 42 ] The authors suggested that T cell depletion by fludarabine was responsible for the sudden transformation in the biological course and behavior of the SCC. Another study of cladribine and second cancers in patients with CLL did not demonstrate increase in risk of second malignancies in CLL except for lung cancer.…”

Melanoma and non‐melanoma skin cancers in hairy cell leukaemia: a Surveillance, Epidemiology and End Results population analysis and the 30‐year experience at Memorial Sloan Kettering Cancer Center

“…The increased risk of cutaneous malignancies in CLL may be related to abnormal immune surveillance inherent to CLL itself, a relative photosensitivity of CLL patients, increased medical contact and thus earlier diagnosis, and/or an effect of immunosuppressive treatments commonly administered for CLL (Buschfort et al, 1997;Robak et al, 2004). This association is clinically relevant as both melanoma and NMSCs are not only more common, but also potentially more aggressive in CLL patients compared to the general population (Bridges & Steinberg, 1986;Hartley et al, 1996;Davidovitz et al, 1997;Larsen et al, 2002;Royle et al, 2011).…”