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Interferon-alpha (IFN-α) has a diverse range of activities that can be used in the treatment of haematological malignancies.

IFN-α has immunomodulatory [1, 2] and anti-angiogenic properties [3] that may indirectly influence tumour growth. IFN-α directly affects cell growth by causing cell cycle arrest in G1 [4, 5] and can induce apoptosis [6]. IFN-α can also induce differentiation of a wide range of normal and malignant cells [7]. This pleiotropic cytokine has clinical activity in a variety of haematological malignancies including lymphoproliferative disorders. The availability of recombinant IFN-α2a and IFN-α2b has opened the way for clinical studies in different indications. In the 1980s there was great enthusiasm for IFN-α in the treatment of hairy cell leukaemia (HCL), multiple myeloma (MM) and follicular lymphoma (FL). However, the side-effects and the cost of this treatment have always been a concern and have prompted re-evaluation of its clinical benefit. Moreover, in all these diseases, newer agents have shown a high efficacy/toxicity ratio and are currently used in preference to IFN-α in a majority of cases. Therefore, it is of interest to summarise the current results and use of IFN-α in lymphoproliferative disorders.


In 1984, Quesada and colleagues [8] published the results of partially purified IFN-α in the treatment of 7 patients with HCL. This publication initiated a new era in the treatment of this rare chronic B-cell lymphoproliferative disorder, which until that time could only be treated by splenectomy. A large multi-centre study on 195 patients confirmed that IFN-α has activity in HCL, with 82% overall response rate [9] but complete remissions were rare (7%); most responses were partial and were of relatively short duration if unmaintained. Although relapses occurred, patients could be re-treated with IFN-α and survival rates were greatly improved [10]. The estimated survival of patients treated with IFN-α was 85–90% at 5 years [9–11]. IFN-α was used at relatively low doses (3 million units 3 times a week) for HCL.

Maintenance therapy with IFN-α has been shown to delay relapses, is reasonably well tolerated by most patients and is not associated with late development of resistance [12]. Moreover, haematological response can improve with time on treatment. However, this strategy raises the issue of the long-term toxicity of IFN-α. Lower doses of IFN-α (≤1 million units; MU) have been shown to be less toxic but less effective [13].

The introduction of purine analogues completely changed the management of HCL since 2-deoxycoformycin (Pentostatin) and 2-chloro-deoxy adenosine (2-CDA) (Cladribine) have been found to be more effective with longer duration of remissions following a short course of therapy.

A randomised study compared IFN-α (3 MU 3 times a week) vs. deoxycoformycin (4 mg/m2 every 2 weeks) in 313 ...

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