EFFECT OF ALL-TRANS-RETINOIC ACID ALONE OR IN COMBINATION WITH CHEMOTHERAPY IN NEWLY-DIAGNOSED ACUTE PROMYELOCYTIC LEUKEMIA

Between February 1992 and November 1996 we treated 30 newly diagnosed acute promyelocytic leukaemia (APL) patients either with oral all-tran s-retinoic acid (ATRA) alone (45 mg m(-2)) or with a simultaneous comb ination of ATRA (45 mg m(-2)), daunorubicin (DNR, 50 mg/m(-2) for 3 da ys) and cytosine arabinoside (ARA-C, 200 mg m(-2) for 7 days). There w ere 15 patients in each group. Patients with a white blood cell count < 5 x 10(9)/l at diagnosis received only ATRA as an induction therapy. Patients with initial white blood cell count > 5 x 10(9)/l received a combination of ATRA, DNR and ARA-C as an induction therapy. Within th e first 20 days of induction, there were two early deaths in the group of patients receiving only ATRA, and six early deaths in the group of patients treated with a combination of ATRA and chemotherapy. Ten out of 13 patients (76.9%) receiving ATRA only achieved complete remissio n (CR) whereas seven out of nine patients (77.8%) receiving ATRA with chemotherapy achieved CR. Initial median peripheral white blood cell c ounts were significantly lower in the group of patients treated with A TRA alone (2.3 x 10(9)/l) than in the group of patients receiving ATRA and chemotherapy (14.0 x 10(9)/l). Morphological evidence of differen tiation was noted in all patients entering CR. Patients in both groups who achieved CR received one course of standard '3+7' chemotherapy (D NR 45 mg m(-2), 1-3 days, ARA-C 200 mg m(-2), 1-7 days) followed by tw o courses of standard '2+5' chemotherapy (DNR 50 mg m(-2) 1-2 days, AR A-C 200 mg m(-2) 1-5 days) as a consolidation therapy. Patients not ac hieving remission (three out of 13 in the ATRA group and two out of ni ne in ATRA+chemotherapy group) did not respond to salvage chemotherapy and all died within 3 months of diagnosis. Only one out of 10 patient s (10%) in CR, treated with ATRA is in relapse after 18 months. In pat ients treated with ATRA alone two out of 10 (20%) survived 58 months f ollowing diagnosis whereas in the ATRA+chemotherapy group one out of s even has already survived their 58th month since diagnosis. Four out o f eight patients with an early death died of retinoic acid syndrome. O ther toxicities due to ATRA were minimal (cheilitis, xerosis, dermatit is, diarrhoea, liver damage or pseudotumor cerebri).