All‐trans Retinoic Acid (Atra) in the Treatment of Acute Promyelocytic Leukemia (Apl)

Abstract

Acute promyelocytic leukemia is characterized by the reciprocal translocation of chromosomes 15 and 17. All‐trans retinoic acid (ATRA) efficiently induces differentiation of the abnormal promyelocytes. In this study, we had used ATRA as the primary induction therapy for 17 newly diagnosed patients, and as the salvage therapy for 11 patients who relapsed from or were resistant to chemotherapy. All patients received subsequent consolidation chemotherapy. Complete remission (CR) rate, early death rate (within 28 days of diagnosis) were then compared to an historical control of 50 APL patients treated with combination chemotherapy; and event‐free survival of the 17 newly diagnosed patients was compared to the historical control. In the ATRA group, 26 of the 28 patients (93 per cent) attained complete remission. Two of 28 (7 per cent) died within 28 days of ATRA therapy. There was no case of primary resistance to ATRA. Combination chemotherapy was added to ATRA in five patients due to rapidly increasing leucocyte count. There was one case of retinoic acid syndrome which resolved with steroid. When compared to the 50 cases of historical control, there is significant improvement in the overall CR rate (92 per cent versus 59 per cent, p=0·001) and a significant reduction in the early mortality rate (7 per cent versus 41 per cent, p=0·001). Moreover, when the survival result of the 17 newly diagnosed patients were compared with the control, there is a significant improvement in the projected EFS at 3 years (64 per cent versus 25 per cent, p=0·007). In conclusion, ATRA was showm to improve the CR rate, reduce induction mortality and significantly prolong the event‐free survival.

Treatment‐related deaths during induction and first remission of acute myeloid leukaemia in children treated on the Tenth Medical Research Council Acute Myeloid Leukaemia Trial (MRC AML10)

“…It is surprising to see that there were no haemorrhagic deaths of those children with promyelocytic (M3) AML (0/27), as it is with this particular subtype of AML that disseminated intravascular coagulation is a risk. However, the early institution of therapy with all‐ trans retinoic acid (ATRA) has certainly reduced this particular cause of early death (Bapna et al , 1998; Chim et al , 1996). It is possible that haemorrhagic deaths could be prevented if children were identified as being at particular risk of haemorrhage, and were very carefully monitored, especially with frequent clotting parameters and platelet counts.…”

Epigenetic inactivation ofDAPK1,p14ARF,mir-34aand-34b/cin acute promyelocytic leukaemia

“…Projected 5-year overall survival (OS) was 68%. All patients received ATRA induction and daunorubicin as induction therapy 3. The study has been approved by Institutional Review Board of Queen Mary Hospital, and written informed consent was obtained.…”

“…Corepressors including histone deacetylase and DNA methyltransferase are recruited by PML–RARα resulting in local chromatin condensation and transcriptional suppression 2. All-trans retinoic acid (ATRA) and arsenic trioxide are effective treatments for APL 3 4…”

Epigenetic dysregulation of the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in acute leukaemias

“…Induction of APL with all-trans retinoic acid (ATRA) was administered at 45 mg/m 2 /day until complete remission (CR) 20. Post-CR consolidation comprised two courses of daunorubicin (50 mg/m 2 /day × 2) and cytosine arabinoside (100 mg/m 2 /day × 5).…”