Table 1.

Treatment protocol COALL-92

Element/drug
Dose
Days given in low risk
Days given in high risk
Prephase    
    Daunorubicin—1 h/24 h INF   36 mg/m2  Day 7   Day 7  
    Methotrexate—IT*  12 mg    
Induction    
    Vincristine—IV   1.5 mg/m2 (maximum, 2 mg)   Days 1, 8, 15, 22   Days 1, 8, 15, 22  
    Daunorubicin—IV   36 mg/m2  Days 1,8, 15   Days 1, 8, 15  
    Methylprednisolone—PO   60 mg/m2 per day   Days 1-28   Days 1-28  
Intensification    
    Cyclophosphamide—IV   900 mg/m2  None   Days 29, 43  
    Methotrexate—24 h INF   1000 mg/m2  Days 29, 43, 78   Days 30, 44, 57, 71  
    L-asparaginase—IV   45 000 U/m2  Days 31, 59, 80   Days 32, 46, 87, 108  
    VM-26—IV   165 mg/m2  Day 45   Days 59, 73  
    Cytarabine—IV   300 mg/m2  Day 45   Days 59, 73  
    HD cytarabine—IV   3000 mg/m2 × 2   Days 57, 58   Days 85, 86, 106, 107  
    Mercaptopurine—PO   100 mg/m2 per day   Days 29-35, 78-84   Days 43-49, 57-63  
    Thioguanine—PO   100 mg/mg2 per day   Days 43-49   Days 71-77  
    Methotrexate—IT*  12 mg   Days 29, 43, 57, 78   Days 29, 43, 57, 71  
CNS prophylaxis    
    Mercaptopurine—PO   50 mg/m2 per day   Days 92-120   Days 127-155  
    Methotrexate—IT*  12 mg   Days 92, 95, 106, 109   Days 127, 130, 134, 138  
    Cranial irradiation     C-/pre-B-ALL + WBC > 25/50 × 109/L and all T-ALL: CRT 18 Gy§ 
Reinduction    
    Vincristine—IV   1.5 mg/m2 (maximum, 2 mg)   Days 1, 8   Days 1, 8, 22, 29  
    Doxorubicin—IV   30 mg/m2  Days 1, 8   Days 1, 8, 22, 29  
    L-asparaginase—IV   45 000 U/m2  Days 2, 9   Days 9, 30  
    Dexamethasone—PO   10 mg/m2 per day   Days 1-14   Days 1-14, 22-35  
    Cyclophosphamide—IV   900 mg/m2  Day 15   Days 36, 50  
    Cytarabine—IV   90 mg/m2 per day   Days 16-19   Days 37-40, 51-54  
    Thioguanine—PO   100 mg/m2 per day   Days 15-21   Days 36-42, 51-56  
    Methotrexate—IT   12 mg   Days 1, 15, 29   Days 1, 22, 36  
Maintenance    
    Mercaptopurine or thioguanine—PO   Dose adjusted to WBC (2-3 × 109/L)   Daily   Daily  
    Methotrexate—PO   Dose adjusted to WBC (2-3 × 109/L)   Weekly   Weekly  
    Methotrexate—IT
 		 12 mg*
 		 Twice/month 3, 6, 9 of MT
 		 Twice/month 3, 6, 9 of MT if no CRT given
 
Element/drug
Dose
Days given in low risk
Days given in high risk
Prephase    
    Daunorubicin—1 h/24 h INF   36 mg/m2  Day 7   Day 7  
    Methotrexate—IT*  12 mg    
Induction    
    Vincristine—IV   1.5 mg/m2 (maximum, 2 mg)   Days 1, 8, 15, 22   Days 1, 8, 15, 22  
    Daunorubicin—IV   36 mg/m2  Days 1,8, 15   Days 1, 8, 15  
    Methylprednisolone—PO   60 mg/m2 per day   Days 1-28   Days 1-28  
Intensification    
    Cyclophosphamide—IV   900 mg/m2  None   Days 29, 43  
    Methotrexate—24 h INF   1000 mg/m2  Days 29, 43, 78   Days 30, 44, 57, 71  
    L-asparaginase—IV   45 000 U/m2  Days 31, 59, 80   Days 32, 46, 87, 108  
    VM-26—IV   165 mg/m2  Day 45   Days 59, 73  
    Cytarabine—IV   300 mg/m2  Day 45   Days 59, 73  
    HD cytarabine—IV   3000 mg/m2 × 2   Days 57, 58   Days 85, 86, 106, 107  
    Mercaptopurine—PO   100 mg/m2 per day   Days 29-35, 78-84   Days 43-49, 57-63  
    Thioguanine—PO   100 mg/mg2 per day   Days 43-49   Days 71-77  
    Methotrexate—IT*  12 mg   Days 29, 43, 57, 78   Days 29, 43, 57, 71  
CNS prophylaxis    
    Mercaptopurine—PO   50 mg/m2 per day   Days 92-120   Days 127-155  
    Methotrexate—IT*  12 mg   Days 92, 95, 106, 109   Days 127, 130, 134, 138  
    Cranial irradiation     C-/pre-B-ALL + WBC > 25/50 × 109/L and all T-ALL: CRT 18 Gy§ 
Reinduction    
    Vincristine—IV   1.5 mg/m2 (maximum, 2 mg)   Days 1, 8   Days 1, 8, 22, 29  
    Doxorubicin—IV   30 mg/m2  Days 1, 8   Days 1, 8, 22, 29  
    L-asparaginase—IV   45 000 U/m2  Days 2, 9   Days 9, 30  
    Dexamethasone—PO   10 mg/m2 per day   Days 1-14   Days 1-14, 22-35  
    Cyclophosphamide—IV   900 mg/m2  Day 15   Days 36, 50  
    Cytarabine—IV   90 mg/m2 per day   Days 16-19   Days 37-40, 51-54  
    Thioguanine—PO   100 mg/m2 per day   Days 15-21   Days 36-42, 51-56  
    Methotrexate—IT   12 mg   Days 1, 15, 29   Days 1, 22, 36  
Maintenance    
    Mercaptopurine or thioguanine—PO   Dose adjusted to WBC (2-3 × 109/L)   Daily   Daily  
    Methotrexate—PO   Dose adjusted to WBC (2-3 × 109/L)   Weekly   Weekly  
    Methotrexate—IT
 		 12 mg*
 		 Twice/month 3, 6, 9 of MT
 		 Twice/month 3, 6, 9 of MT if no CRT given
 

INF indicates infusion; IT, intrathecally; IV, intravenously; and PO, orally.

*

Doses were adjusted for children younger than 3 years.

§

CRT indicates cranial irradiation; doses were adjusted for children younger than 3 years.

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