Summary Classic hairy cell leukemia (HCL) is a rare indolent B‑cell-lymphoproliferative disorder, first described as a distinct disease entity in 1958. After more than two decades without effective chemotherapeutic options and a dismal prognosis of less than 5 years, only the introduction of interferon‑α (IFN‑α) allowed for response rates between 80–90 % and survival improvement. Nowadays, however, patients are rarely treated with IFN-α as purine analogues were found to be highly effective in HCL facilitating a near normal life span in most cases. Moreover, novel therapeutic tools for patients with relapsed or refractory disease after purine analogues have emerged such as rituximab and, more recently, vemurafenib. In the absence of long-term safety data for these novel agents, however, IFN-α may still represent a viable therapeutic option when the profound immunosuppressive side effects of purine analogues are to be avoided. We herein report a HCL patient, who has received multiple lines of therapy, including pentostatin, cladribine, and a total of 164 months of treatment with IFN‑α yielding long-term disease control. Our case illustrates that long-term administration of IFN-α with adequate dose-adjustments according to toxicity and disease activity is feasible in HCL and may still be a viable therapeutic option when purine analogues are considered unsuitable.

Classic hairy cell leukemia (HCL) is an uncommon hematologic malignancy characterized by an excellent prognosis since purine analogues (PA), such as cladribine (2-CdA), have been introduced in the 1990s. However, most data on long-term outcomes is gathered from patients treated with PA first-line or include limited information on previous treatment outcomes, i.e., Interferon-α (IFN-α). Survival curves from previous series did not reach a plateau, indicating that nearly all patients ultimately relapse. Yet, overall survival (OS) data were rarely corrected for life expectancy of the general population. We here report 83 consecutive HCL patients treated between 1983 and 2017 at the University Center in Innsbruck, Austria. Median follow-up was 170 months (1–498). IFN-α, the first-line treatment of choice before 1990, was administered to 24 patients, achieving an overall response rate (ORR) of 86% and an unconfirmed complete remission (CRu) in 23%. All these patients relapsed after a median progression-free survival (PFS) of 30 months (3–80), but either remained drug-sensitive upon re-exposure to IFN-α or were successfully salvaged with PA. All 42 patients exposed to first-line 2-CdA responded (ORR of 100%). Sixteen patients received two to four successive courses of PA with a continuous decrease in the response quality (CRu rate 85.7% 1st-line vs. 41.5% 3rd-line treatment). Median PFS was not reached in both treatment-naïve patients and those retreated at first relapse. Although pretreatment with IFN-α was associated with a shortened median PFS of 81 months (43–118) after PA therapy, this tendency of inferior PFS did not result in inferior OS. OS of all 83 patients was excellent and equivalent to that of age-, sex-, and diagnostic period-matched controls from the Tyrolean general population (standardized mortality ratio 0.8), regardless of their age at diagnosis or whether they were diagnosed until or after the year 2000. These results confirm that HCL patients may look forward to a normal lifespan when treated with PA irrespective of their pretreatment history.