Treatment of adult T-cell leukaemia/lymphoma: current strategy and future perspectives

Human T-cell leukaemia virus type I (HTLV-I) associated adult T-cell leukaemia/lymphoma (ATL) carries a very poor prognosis due to an intrinsic resistance of leukaemic cells to conventional or even high doses of chemotherapy and to an associated severe immunosuppression. Therefore, the potential role of conventional chemotherapy, high dose chemotherapy with autologous or allogeneic bone marrow transplantation remains to be defined. Important progress was achieved in the treatment of ATL with the combination of zidovudine (AZT) and interferon-alpha (IFN) which produces a high response rate in ATL patients with minimal side effects. This treatment seems to prolong the survival of patients much more than intensive chemotherapy. The success of this potentially anti-retroviral approach in the treatment of ATL suggests the existence of continuous HTLV-I replication in vivo. These encouraging results may be improved by the use of higher doses of AZT and IFN combined with other anti-retroviral agents. However, since cure seems still elusive, new therapeutic approaches or new combinations are required. For example, biological mediators such as retinoid acid, which induces apoptosis of ATL cells in vitro, may reduce drug resistance and stimulates immunity to restore anti-tumour activity against ATL cells. Alternatively, immunotherapy with anti-interleukin-2 receptor monoclonal antibodies or injection of cytotoxic T-cells directed against virus antigens could be interesting approaches which may merit further investigations in the near future. Finally, the recent demonstration that the combination of arsenic trioxide (As) and IFN induces a specific degradation of the viral transactivator Tax followed by cell cycle arrest and apoptosis of HTLV-I positive cells may constitute a valuable addition to ATL treatment.