Risk Of Second Malignancies

In an epidemiological study of HCL in Los Angeles County in 1990, it was noted that patients with a history of HCL were more than twice as likely as other cancer patients to have multiple cancer diagnoses.5 Since that time, multiple studies have confirmed that HCL patients have an increased risk for secondary malignancies. The rationale for this observation is probably dual. The primary treatment of HCL involves the use of nucleoside analogs, which lead to prolonged immunosuppression, with lower than normal numbers of CD4+ cells for more than 3.5 years.1819 This prolonged immunosuppression leads to an increase in second malignancies.19 Cheson et al. looked at patients with either chronic lymphocytic leukemia (CLL) or HCL who had undergone treatment with Nucleoside Analogs and found a total of 150 secondary cancers in 146 patients. Most of these cases were solid tumors, with a higher than expected frequency of prostate cancer.20 In a study from British Columbia, Au et al. reported that of 117 patients with HCL diagnosed between 1976 and 1996, 30.7% had at least one additional malignancy. Twenty percent were diagnosed either at the same time or within a few years of the diagnosis of HCL, with a peak incidence at 2 years afterwards. All secondary malignancies were solid tumors.21

Interestingly, previous studies of other immunocom-promized populations found an increased incidence of hematologic malignancies, yet more solid tumors were found in patients with HCL. They were detected prior to or concomitant with the diagnosis of HCL. There is one case report of a patient with a myeloproliferative disorder (essential thrombocythemia) treated with hydrox-yurea who later developed HCL.22 There have been two reports of pre-existing polycythemia vera followed by a diagnosis of HCL.23

Interferon alpha is an effective treatment for HCL. This suggests that the immune system may help modulate disease progression.2425 Multiple tumors were found in some studies either prior to or concomitant with the diagnosis of HCL, raising the suspicion that there may be an underlying impaired immune response in patients with HCL.26

Not all studies support the theory that patients with HCL are at an increased risk for second malignancies. The following reported that the incidence of second malignancies was not significantly higher than expected. Fifty-four of 1,022 patients in the Italian Cooperative Group for the Study of HCL developed second cancers; this was not significantly higher than the expected rate, although the incidence of lymphoid neoplasms was significantly higher.27 Data on 350 patients with HCL obtained from the M.D. Anderson Cancer Center Cancer Registry found that, although there was an increase in the number of second malignancies, statistical significance was not achieved, and the excess malignancies were not thought to be associated with therapy.28

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