Clinical application of all-trans retinoic acid (tretinoin) for adult T-cell leukaemia.

Abstract

It has been reported that retinoic acid (RA) has an antiproliferative effect and an apoptosis-inducible effect for adult T-cell leukaemia (ATL) in vitro ( Maeda et al, 1996 ; Miyatake & Maeda, 1997). We here confirm the clinical effects of all-trans retinoic acid (ATRA) (Tretinoin, Roche) in an ATL patient. A 32-year-old Japanese man was referred to our hospital for treatment of uveitis. Laboratory study showed that the patient's white blood cell count (WBC) was 13·9 × 109/l with 10% polymorphonuclear cells (typical ATL cells), antibodies to human T-cell lymphocytotrophic virus (HTLV)-I were positive and serum calcium was 2·71 m m. Lactate dehydrogenase was within the normal range. A surface marker analysis of peripheral blood mononuclear cells (PBMCs) showed increased CD4 antigen (74·8% positive) and CD25 antigen (47·4% positive). Monoclonal integration of HTLV-I proviral DNA was detected in PBMCs by the inverse polymerase chain reaction (PCR) method ( Takemoto et al, 1994 ). A diagnosis of chronic ATL was then made. Informed consent was obtained according to the Declaration of Helsinki. We decided to select retinoid therapy with Tretinoin (60 mg/d p.o.). The number of ATL cells seen in the peripheral blood decreased gradually. At day 25 of Tretinoin treatment, the patient's WBC was 6·8 × 109/l with 5% ATL cells. Interestingly, the expression of CD25 on PBMCs had decreased significantly (15·7% positive) at day 25 of Tretinoin treatment. Furthermore, the monoclonal integration band of HTLV-I by inverse PCR was not detected at this time. With the administration of Tretinoin, the patient's general fatigue was improved and his low-grade fever disappeared. Moreover, his uveitis improved completely in response to treatment with Tretinoin. Thus, RA may be a useful agent for HTLV-I-associated disorders, including ATL, HAM (HTLV-I-associated myelopathy), HAAP (HTLV-I-associated arthropathy), HAB (HTLV-I-associated bronchopathy) and HAU (HTLV-I-associated uveitis).