All-trans retinoic acid therapy of acute promyelocytic leukemia in children: clinical results in Russia and Belarus.

The use of all-trans retinoic acid (ATRA) represents the first successful d ifferentiation-base therapy of tumors. It forces terminal maturation of mal ignant promyelocytes bearing the t (15;17) translocation but not other abno rmalities. Such treatment brought a dramatic improvement in cure rates in a cute promyelocytic leukemia: protocol APL-93 yielded a complete remission i n about 90% and EFS about 65% in adults. The results of APL treatment with ATRA in children are not published. Since 1995 we have treated 23 children (F/M = 1.1:1) aged 6 to 19 years (median 12) with newly diagnosed APL. Ther e were 22 cases of typical M3 and 1 M3v subvariants. In all 21 cases where cytogenetics was performed t(15;17) (q34;q34) was demonstrated. The protoco l consisted of two courses of AraC (100 mg/m(2) bd for 7 days and DNR (60 m g/m(2) for 3 days, consolidation with HD AraC (1 g/m(2) bs 4 days)+DNR 45 m g/m(2) and maintenance with GMP+Mtx for a total of 24 months tone of the br anches of the APL-93 protocol). The patients received ATRA in dose 45 mg/m( 2) during induction until 45th day or CR. All 23 patients achieved CR. ATRA syndrome occurred in 4 patients (17%) and was successfully treated (Dexa 2 0 mg/m(2)/d during 1-3 weeks). None had serious bleeding and infection comp lications. The compliance was satisfactory. One patient relapsed at the 28t h month of remission and died; 22 are alive with a median follow-up of 24 m onths. The actuarial EFS at 4 years is 95.5%. These pilot results confirm h igh efficacy and manageable toxicity of ATRAL-based treatment of APL in chi ldren.