Adult T cell leukaemia: a review of established and new treatments.
Adult T cell leukaemia (ATL) is an aggressive clonal malignancy of mature activated T cells, caused by the human T cell lymphotropic virus type I (HTLV-I) infection. ATL continues to have a very bad prognosis because of the intrinsic resistance of leukaemic cells to conventional or even high-dose chemotherapy and because of the associated severe immunosuppression. Even though conventional chemotherapy remains the standard treatment in acute and lymphomatous types of the disease, the benefit of this intensive approach is not well established in chronic and smouldering ATL. Combination chemotherapy regimens, in particular those designed for the treatment of aggressive non-Hodgkin's lymphomas or acute lymphoblastic leukaemia, have little effect in the treatment of ATL. Different combination regimens of conventional chemotherapy have been investigated in Japan, and recent results of intensive induction therapy showed a complete remission (CR) rate of about 40% in the aggressive forms of the disease. However, most of the patients relapsed and eventually died. Allogeneic bone marrow transplantation has been used in the treatment of a very small number of patients with ATL. High toxicity and transplant-related mortality were observed in these immunocompromised patients. New cytotoxic agents have also been used in pilot phase II studies in refractory or relapsed ATL patients, but significant results have only been observed with deoxycoformycin. Recently, promising results have been obtained with anti-Tac monoclonal antibodies directed against the alpha-chain of the interleukin-2 receptor (CD25), which is highly expressed on ATL cells but not on normal resting lymphocytes. Promising results were also reported in 2 phase II studies with combination therapy comprising the antiretroviral agent zidovudine and interferon-alpha (IFNalpha). In previously untreated patients with acute ATL, high and rapid (usually within 2 weeks) response rates were reported. In contrast, in lymphomatous ATL, both studies suggested a milder and slower effect of zidovudine and IFNalpha. In this case, this combination may be used as maintenance therapy after a CR or good partial response induced by polychemotherapy. Since cross resistance between chemotherapy and zidovudine and IFNalpha does not seem to occur, a combination with best induction polychemotherapy is warranted.
Hermine
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Department of Hematology and CNRS URA 1461, Necker University Hospital, Paris, France. hermine@necker.fr
Wattel
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E
Gessain
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Bazarbachi
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