Interferon as an alternative to purine analogues in the treatment of hairy cell leukaemia

We read with interest the recent article regarding the long-term follow-up of 233 patients with hairy cell leukaemia (HCL) treated initially with pentostatin or cladribine (Else et al, 2009). The authors presented a 97% overall response rate after treatment with either drug with a median relapse-free survival of 16 years. The results look encouraging; however, they offer some difficulties in interpretation.

Considering the list of centres participating in the study, the number of included patients seems rather small. Were some patients given alternative treatments, such as Interferon or splenectomy, and if so what was the authors’ decision algorithm for choosing alternative treatments? What was the outcome of patients not included in the study treated with pentostatin or cladribine in the observed time period?

The analysis by Else et al (2009) did not show an increased risk for secondary malignancies after treatment with purine analogues, but this point remains a matter of debate in HCL patients. Several studies on purine analogues in HCL (Cheson et al, 1998; Saven et al, 1998; Chadha et al, 2005) and the largest study focusing primarily on secondary cancer in HCL (Hisada et al, 2007) have shown a higher rate of secondary malignancies in HCL patients. Regarding the data of Hisada et al (2007), the rate seems to increase in parallel to the introduction of purine analogues. Given that patients with HCL have an almost normal life expectancy and the peak incidence of diagnosis is around 55 years, these patients are at long-term risk for secondary malignancies. In particular, patients with early relapses after initial treatment with several cycles of purine analogues may be at increased risk for later malignancies. In fact, as in other series, one third of patients had to be retreated 5 years after the initial treatment (Goodman et al, 2003; Jehn et al, 2004) and the disease-free survival tended to be shorter after each cycle of purine analogues in the previous studies. We therefore believe that purine analogues should be cautiously reused in non-responders and younger patients with early relapses. We and others showed very good long-time survival rates with relatively few side effects in HCL patients treated with low-dose interferon-α during induction and maintenance (Damasio et al, 2000; Benz et al, 2009). In our opinion, because of the lack of available alternative treatments, interferon-α should still be considered in non-responders and patients with early relapses to diminish the risk of secondary cancers which might occur even decades after therapy. Although interferon-α treatment cannot cure HCL, it may be less harmful than purine analogues in this extremely long-term disease.

Acknowledgements

None.

Conflict of interest

None.