Longterm Complications

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The initial concern for patients treated with the purine nucleosides was for an increased risk of infection and the development of second malignancies due to the profound long-term suppression of CD4 and CD8 lym-phocytes.27 28 However, a significant increase in infections is not seen in patients who have responded to treatment and have normal neutrophil counts. In our series, during the 7-year median follow-up, only herpes zoster was seen in remission patients.24

A variety of second malignancies have been reported in patients with HCL both prior to and following diagnosis and treatment. They include both solid tumors and malignancies of the lymphoid and hematopoietic system.3 These have been reported in the pre-chemotherapy era, as well as in long-term follow-up after treatment with interferon and purine antimetabolites. Several papers have tried to answer the question of whether the risk of second malignancy is inherently increased in hairy cell patients and/or does treatment increase the risk. In a retrospective review of 117 patients from British Columbia with a median follow-up of 5 years, there were 44 malignancies in 36

patients.29 This was greater than expected when compared to age-matched controls, but there did not appear to be a relationship to treatment with interferon or purine analogs. In a study from the University of Chicago of HCL patients who received interferon, there were 13 malignancies, including six hematologic, among 69 patients.30 This was more than the expected three patients, though whether this increase was drug or disease related could not be determined.

In the multicenter study comparing interferon with pentostatin treatment,23 241 patients were followed; 39 malignancies developed, including eight hemato-logic malignancies. This was slightly greater than the 26 expected, but when solid tumors alone were evaluated, there was no difference compared to age-matched controls. In a retrospective review of 725 Italian HCL patients, including patients treated with interferon and chemotherapy, the incidence of second malignancies was only 3.7%, not significantly greater than expected in this older population.31 It is thus not yet determined whether HCL is associated with second malignancies or the possible role of treatment in their development. Long-term evaluation will be needed to define the true risk, but as of now second malignancies have not impacted survival.

In summary, as the result of effective initial treatment of HCL patients and the ability to retreat when patients relapse, survival was similar to that predicted for the general population. Additionally, long-term complications after treatment are not frequent and do not affect overall survival.

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