RISK-ADAPTED COMBINED THERAPY WITH ARSENIC TRIOXIDE AND ALL-TRANS-RETINOIC ACID FOR DE NOVO ACUTE PROMYELOCYTIC LEUKAEMIA

Introduction. Non-chemotherapy for acute promyelocytic leukaemia (APL) with a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) provides for a high patient survival rate at lesser toxicity as effectively or superior to standard chemotherapy programmes. Aim - assessment of the ATO-ATRA risk-adapted exposure protocol in management of de novo acute promyelocytic leucaemia. Materials and methods. A prospective study included 51 primary APL patients aged 18-76 years. The program included remission induction (ATO 0.15 mg/kg intravenously, ATRA 45 mg/m(2) orally) for 30-60 days in a low-risk (until remission) and 60 days - in a high-risk cohort that had idarubicin therapy added on days 2 and 4. Remission consolidation was attained with four (low-risk) or five (high-risk) courses. Minimal residual disease was monitored with real-time PCR at all phases. Results. The high-risk cohort was assigned 15 (29.4 %), the low-risk cohort - 36 (70.6 %) patients. Therapy induction till APL morphological remission was performed in 48/51 (94 %) patients. Molecular APL remission was achieved in 47 (92 %) patients, 100 % in the low-risk and 80 % in high-risk cohort. Early mortality was 6 % (n = 3), death in remission - 2 % (n = 1). Differentiation syndrome (DS) occurred in 16 (31.7 %) patients, more frequently in the high-risk vs. low-risk cohort (53.3 % and 22.2 %, respectively, p = 0.05; odds ratio 4.0 [1.1-14.4]). DS developed on days 1-20 (3 days median) of therapy. DS risk factors: a high-risk status, haemorrhagic syndrome and infection at the disease onset. A median follow-up time in survivors was 12.9 months (2.5-34.3), a six-month overall survival - 92 % (95 % CI: 85-100 %). A six-month overall survival was 100 and 73 % in the low- and high-risk cohorts, respectively (95 % CI: 54-100 %, p = 0.001). APL relapse not registered, 47 (92 %) patients survived and achieved the first molecular remission. Conclusion. A differentiated risk-adapted approach to APL therapy with cytostatic treatment added in high-risk patients only provided for a 100 % molecular remission and relapse-free survival. Therapy failures (early mortality and death in remission) affected high-risk patients due to a severe individual condition at the time of APL diagnosis.