Summary. The optimal treatment of acute promyelocytic leukaemia (APL) recurring from relapses successfully treated using arsenic trioxide (As 2 O 3 ) is undefined. Three APL patients relapsing from As 2 O 3 -induced remission were studied. Re-treatment with As 2 O 3 failed in one patient in third relapse, and resulted in morphological but not molecular remission in another patient. Combination therapy with As 2 O 3 and all-trans retinoic acid (ATRA), however, resulted in morphological and molecular remission in all three cases, with a follow-up time ranging from 6 to 16 months. Our results suggest a synergistic therapeutic effect between As 2 O 3 and ATRA in APL in advanced relapse.Keywords: relapsed APL, arsenic trioxide, all-trans retinoic acid.Arsenic trioxide (As 2 O 3 ) has been shown to be an effective treatment for patients with relapsed acute promyelocytic leukaemia (APL) (Shen et al, 1997;Soignet et al, 1998;Niu et al, 1999). However, for patients relapsing again after As 2 O 3 -induced remissions, the prognosis is poor. Protocols comprising As 2 O 3 , chemotherapy, all-trans retinoic acid (ATRA) and their various combinations have limited success (Niu et al, 1999). Therefore, there is a need to define effective treatment strategies for these patients.In a cohort of 17 consecutive cases of APL in relapse treated with intravenous As 2 O 3 followed by consolidation with idarubicin alone (Kwong et al, 2001), five patients had relapsed again. Two patients died of central nervous system bleeding before further treatment could be given (Au et al, 2000). The remaining three patients were successfully treated with a combination of As 2 O 3 and ATRA, and are the subjects of this report.
PATIENTS AND RESULTSCase 1 was a 41-year-old woman treated with As 2 O 3 for APL in second relapse (Table I). On reaching a third complete remission (CR3), she was consolidated with idarubicin (Kwong et al, 2001). However, PML/RARA remained positive using a standard reverse transcription polymerase chain reaction (Kwong et al, 1995), with a sensitivity of 1 · 10 )4. A third haematological relapse occurred 15 months later. Re-treatment with As 2 O 3 (10 mg/d) was ineffective, as evidenced by persistent leukaemia (pancytopenia and 40% blasts and promyelocytes in the marrow) after 42 d of therapy. ATRA (45 mg/m 2 /d) was then added. After 2 weeks of combined As 2 O 3 /ATRA treatment, the promyelocytes in the marrow had decreased to 5%. The treatment was stopped after 76 d of As 2 O 3 and 33 d of ATRA. At this point, the marrow was in complete morphological remission, but PML/RARA was still detectable. Three more monthly courses of As 2 O 3 /ATRA (each for 14 d) were administered, with PML/RARA becoming negative after the first course. At the latest follow-up 16 months after CR4, the patient was in haematological and molecular remission.Case 2 was a 21-year-old woman with APL in first relapse, who achieved a CR2 with As 2 O 3 (Table I). PML/ RARA remained positive despite consolidation with idarubicin, and a second haematological rel...