Hairy Cell Leukemia and Secondary Lymphoproliferative Disorders.

Prolonged immunosuppression is generally associated with an increase in incidence of lymphoid cancers. Transplant recipients, primary or genetic immunodeficiencies and patients with the acquired immunodeficiency syndrome (AIDS) have a known increased incidence of lymphoproliferative disorders. Patients who develop hairy cell leukemia (HCL) also have impaired immune function at the T-cell level that is present before definitive therapy. The lack of T-cell responsiveness is due to a decrease in memory T helper cells, abnormal activation of spleen T lymphocytes that behave like tumor infiltrating cells, and selection of oligoclonal T-cell populations with a very restricted and skewed T-cell repertoire. Inadequate antigen presentation may also play a role due to monocytopenia and lack of CD 28 on T-cells. Treatment with purine analogs, particularly pentostatin and cladribine, targets both resting and proliferating lymphocytes. This further impairs immune function by producing a prolonged reduction of normal lymphocytes, mainly CD4 cells, for as long as two years. There are reports of lymphoproliferative disorders as a second malignancy after treatment for HCL. However, it is not clear if treatment with purine analogs can induce second malignancies due to immune suppression. We reviewed the literature for cases of secondary lymphoproliferative disorders in patients treated with and without purine analogues for HCL. Purine analogues do not appear to have an increased risk for a secondary lymphoproliferative disorder. However, a preexisting immunosuppressed state may exist that antecedes the treatment of HCL and predisposes some patients to secondary lymphoproliferative disorders.