Hairy cell leukemia is one of the rarest forms of leukemia, and in the United States the incidence is 3.2-3.3/million population/year. The median age at diagnosis is 58 years and the disease is four-times more common in men than in women. The disease is more common in Whites than in Blacks or Asians. The likelihood of developing the disease increases up to the age of 40 years and then begins to plateau with the median age at diagnosis being 58 years (57 years for men and 63 years for women). Over the past 30 years the incidence of this disease has not changed but it seems that there is a higher proportion of cases diagnosed than anticipated above the age of 65 years. In this respect, it is possible that in the past cases in the elderly had been either under-estimated or under-reported.

Because of the rarity of this disease there have been few studies related to the etiology. The cause of the disease is still unknown but risk factors may include exposure to pesticides, herbicides and petrol or diesel fuel. There is no association with alcohol or coffee consumption, and employment in farming or woodworking is of borderline significance. Recent investigations report that the duration of farming occupation, and the length of exposure to farming may be important in terms of HCL risk, independent of other exposures. A familial predisposition has also been suggested due to the clustering of cases within families, but whether this is related to genetic or environmental factors is unknown. There has been no consistent human leukocyte (HLA) linkage in these rare cases of familial HCL. Association with a personal history of autoimmune disease is also unclear.

With the development of Pentostatin and Cladribine, most patients have a prolonged survival and there has been much interest in whether these patients will have an increased risk of second malignancies. This could be because HCL patients are inherently predisposed to developing another malignancy or it could be related to immunosuppression secondary to the leukemia or to the nucleoside analogs used to treat the disease. A number of studies have been carried out, primarily from single institutes or based on patients entered on clinical trials, with disparate results. The largest population based study was carried out on 3104 HCL patients identified from 1973 through 2002 through the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program. The average duration of follow-up was 6.5 years (range, 2 months to 29.3 years) and patients had a 1.24 increased incidence of a second malignancy, compared to the general population. The cumulative risk of a second cancer at 10, 20 and 25 years following diagnosis was 13.2%, 24.5% and 31.9%, respectively. Patients had a significantly increased risk of developing Hodgkin disease, non-Hodgkin’s disease and thyroid cancer. The risk of thyroid cancer was in the first 5 years following diagnosis while the risk of lymphoma was still observed after 10 years. Interestingly the patients had a reduced risk of death from lung cancer, cardiovascular and cerebrovascular disease suggesting that these patients probably smoked less than the general population.

This issue still remains somewhat controversial and in a recent study from Scripps Clinic second primary malignancies were reported in 9% of young patients with HCL treated with Cladribine – representing a low, statistically insignificant increased risk (1.60 fold) of developing second cancers. This risk had been estimated to be more in some earlier studies with an observed – to expected ratio of 1.88- 2.03. This data is more reassuring when considering the young age of patients with HCL and the initial concerns in this regard. Thus, it is clearly evident that both Cladribine and Pentostatin are effective treatments for HCL. The majority of patients will achieve complete remission after their first course of therapy which is long–lasting, and retreatment after relapse is often successful using the same agent. However, there was an increased incidence of infections following the diagnosis of HCL, for up to 10 years with the highest risk in the first year following diagnosis. Therefore, it is reasonable that patients have careful follow-up to ensure early treatment of infection or early recognition of a second cancer if it should occur.