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Adult T-cell leukaemia (ATL) is difficult to cure using conventional therapies. Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T-cell leukaemia virus type I (HTLV-I) infected T-cell lines and fresh ATL cells by arsenic trioxide (As 2 O 3 were evaluated by comparison with a series of RA derivatives, Proliferation of four HTLV-I-infected T-cell lines was significantly reduced within 72 h by 1.0 μmol/l As 2 O 3 . Growth of two out of four HTLV-I-infected T-cell lines was also inhibited by 1.0 μmol/l RA. but to a lesser extent than by As 2 O 3 . The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by As 2 O 3 but far less by RA. As described in patients with acute promyelocytic leukaemia. 1.0 μmol/l of As 2 O 3 can be safely achieved in the serum of patients: however, it is. difficult to maintain this concentration of RA, In conclusion, As 2 O 3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA.

The novel defucosylated humanized monoclonal antibody against CC chemokine receptor 4 (CCR4), mogamulizumab, exhibited strong effects on adult T-cell leukemia-lymphoma (ATL) in a phase II clinical study. It has been also reported that mogamulizumab frequently developed cutaneous adverse reactions (CAR) and a close association between CAR and the prognosis. [1] We studied the effects of mogamulizmab on ATL and CAR in 32 patients with ATL. Informed consent was obtained prior to study. Nineteen patients received more than 4 cycles of mogamulizumab therapy. Twenty patients developed an infusion reaction, and eight patients suffered from CAR. These eight patients were administered mogamulizumab more than 4 cycles (median: 7 cycles). The severity of CAR according to CTCAE v3.0 was grade 1 in one patient, 2 in two, 3 in three and 4 in two patients respectively. In six of 8 patients, CARs appeared or most worsened in more than 4 weeks after the last administration. All CARs fortunately subsided later. One patient, however, suffered from toxic epidermal necrolysis and other CARs (erythroderma and generalized exudative erythema in two each patients) prolonged for several months. As for anti-tumor effects with more than 4 cycles of treatments, overall response rate (complete remission (CR) and partial remission (PR)) was 58% (CR: 6, progressive disease (PD): 2) with CAR, and 36% (CR:3, PR:1, stable disease (SD):4, PD:3) without CAR. These results suggest that 1) the incidence of CAR were associated with the frequency of mogamulizumab administration, 2) CARs might be favorable signs of the effect, and 3) follow-up with careful attention to CAR was recommended for at least several months after the finish of treatments.