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ATRA 45mg/m2/d PO Days 1-36 in divided doses
 12mg/m2/d IV(ages 1-60) Days 2,4,6,and 8
 9mg/m2/d IV (ages 61-70)
 6mg/m2/d IV (ages 70)
ATO 0.15mg/kg/d IV Days 9-36 as a 2-hour IV infusion
 Supplemental potassium and magnesium as required to maintain serum levels in the upper half of the respective normal ranges
Prednisone 1mg/kg/d PO Days 1-10 or until WBC count falls below 1x10^9/L or until resolution of differentiation syndrome (whichever   occurs last)
Hemostatic support
 Products administered once or twice daily as required to achieve specified targets
 Platelets > 30x10^9/L
 Normal prothrombin time
 Normal activated partial thromboplastin time
 Fibrinogen > 1.5g/L

Consolidation cycle 1(3-4 wks after the end of induction)

ATRA 45mg/m2/d PO Days 1-28
ATO 0.15mg/kg/d IV Days 1-28

Consolidation cycle 2 (3-4 wks after the end of consolidation cycle 1)

ATRA 45mg/m2/d PO Days 1-7,15-21,29-35
ATO 0.15mg/kg/d IV Days 1-5,8-12,15-19,22-26,29-33

Maintenance: 8 cycles (3-4 wks after the end of consolidation cycle 2)

ATRA 45mg/m2/d PO Days 1-14
MTX 5-15mg/m2/wk PO Days 15-90
6MP 50-90mg/m2/d PO Days 15-90


Illand et al . All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4) Blood August 23, 2012

The treatment of acute promyelocytic leukemia has improved considerably after recognition of the effectiveness of all-trans-retinoic acid (ATRA), anthracycline-based chemotherapy, and arsenic trioxide (ATO). Here we report the use of all 3 agents in combination in an APML4 phase 2 protocol. For induction, ATO was superimposed on an ATRA and idarubicin backbone, with scheduling designed to exploit antileukemic synergy while minimizing cardiotoxicity and the severity of differentiation syndrome. Consolidation comprised 2 cycles of ATRA and ATO without chemotherapy, followed by 2 years of maintenance with ATRA, oral methotrexate, and 6-mercaptopurine. Of 124 evaluable patients, there were 4 (3.2%) early deaths, 118 (95%) hematologic complete remissions, and all 112 patients who commenced consolidation attained molecular complete remission. The 2-year rate for freedom from relapse is 97.5%, failure-free survival 88.1%, and overall survival 93.2%. These outcomes were not influenced by FLT3 mutation status, whereas failure-free survival was correlated with Sanz risk stratification (P[trend] = .03). Compared with our previously reported ATRA/idarubicin-based protocol (APML3), APML4 patients had statistically significantly improved freedom from relapse (P = .006) and failure-free survival (P = .01). In conclusion, the use of ATO in both induction and consolidation achieved excellent outcomes despite a substantial reduction in anthracycline exposure. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12605000070639.