Table 1.

Commonly used first-line chemotherapy regimens for BL in sub-Saharan Africa

RegimenReferenceDrugs*Notes
Prephase    
 39  Cyclophosphamide 500 mg/m2 IV; day 1 Children with malnutrition received cyclophosphamide 300 mg/m2 
40  Methotrexate 12 mg IT; day 1 
23  Cyclophosphamide 300-400 mg/m2 IV; day 1 
Vincristine 1 mg/m2 (max, 2 mg) IV; day 1 
Prednisone 1.5 mg/kg PO; days 1-5 
Low-intensity    
 INCTR 03-06 protocol 33  Cyclophosphamide 1200 mg/m2 IV; day 1 15-d cycles if ANC ≥1.0 × 109 /L and platelets ≥75 × 109/L 
Vincristine 1.4 mg/m2 (max, 2 mg) IV; day 1 3 cycles for low risk (single extra-abdominal site <10 cm) 
Methotrexate 75 mg/m2 IV; day 1 6 cycles for high risk (all others) 
Methotrexate 12 mg IT; days 1 and 8 
Cytarabine 50 mg IT; day 4 
With anthracyclines    
 CHOP 23  Cyclophosphamide 750 mg/m2 IV; day 1 21-d cycles × 6 cycles if ANC ≥1.0 × 109/L and platelets ≥75 × 109 /L 
Doxorubicin 40 mg/m2 IV; day 1 
Vincristine 1 mg/m2 (max, 2 mg) IV; day 1 
Prednisone 1.5 mg/kg PO; days 1-5 
Methotrexate 12 mg IT; day 1 
 JOOTRH protocol 35  Induction-consolidation  
 Cyclophosphamide 1200 mg/m2 IV; days 1, 8, 15, 22, 28, 35  
 Doxorubicin 60 mg/m2 IV; days 1, 22  
 Vincristine 1.5 mg/m2 IV; days 1, 8, 15, 22, 28, 35  
 Methotrexate 7.5 mg/m2 IT; days 1, 8, 15, 22  
 Prednisone PO tapering dose  
Maintenance Maintenance 
 Cyclophosphamide 300 mg/m2 IV; day 1  28-d cycles × 24 mo 
 Vincristine 1.5 mg/m2 IV; day 1  
 Malawi 2012-2014 protocol 36  Cyclophosphamide 40 mg/kg (max, 1.6 g) IV; days 1, 15, 28 Doxorubicin given for only stage III/IV 
Cyclophosphamide 60 mg/kg (max, 2.4 g) IV; day 8 
Doxorubicin 60 mg/m2 IV; days 15, 28 
Vincristine 1.5 mg/m2 (max, 2 mg) IV; days 1, 8, 15, 28 
Prednisone 60 mg/m2 PO; days 1-5 
Methotrexate 12.5 mg IT; day 1, 8, 15, 28 
With high-dose methotrexate    
 GFAOP 2001/2009 protocol 39  Induction Induction 
40   Cyclophosphamide 250 mg/m2 IV; days 1-3  15-d cycles × 2 cycles administered once (1) ANC ≥ 1.0 × 109 /L or ANC ≥ 0.5 × 109 /L and increasing; and (2) platelets ≥ 100 × 109 /L 
 Vincristine 1.5 mg/m2 (max, 2 mg) IV; day 1  Leucovorin given for 12 doses beginning 24 h after methotrexate 
 Methotrexate 1-3 g/m2 IV over 3 h; day 1  Alkaline hydration administered 2 h before and 2 h after methotrexate 
 Leucovorin 15 mg/m2 4× daily PO/IV; days 2-4  Methotrexate 1 g/m2 in 2001 protocol safely escalated to 3 g/m2 in 2009 protocol 
 Prednisone 60 mg/m2 PO; days 2-5  For stage IV with <70% blasts in bone marrow: cyclophosphamide 500 mg/m2 IV, days 1-2; vincristine 2 mg/m2 IV (max 2 mg) IV, Day 1 
 Methotrexate 12 mg IT; days 2 and 6 
Consolidation Consolidation 
 Methotrexate 1-3 g/m2 IV over 3 h; day 1  2 cycles administered once (1) ANC ≥ 1.0 × 109/L or ANC ≥ 0.5 × 109/L and increasing; and (2) platelets ≥ 100 × 109 /L 
 Leucovorin 15 mg/m2 4× daily PO/IV; days 2-4  Leucovorin given for 12 doses beginning 24 h after methotrexate 
 Cytarabine 50 mg/m2 2× daily SC; days 2-6  Alkaline hydration administered 2 h before and 2 h after methotrexate 
 Methotrexate 12 mg IT; day 2  Methotrexate 1 g/m2 in 2001 protocol safely escalated to 3 g/m2 in 2009 protocol 
 Cytarabine 50 mg IT; day 7 
RegimenReferenceDrugs*Notes
Prephase    
 39  Cyclophosphamide 500 mg/m2 IV; day 1 Children with malnutrition received cyclophosphamide 300 mg/m2 
40  Methotrexate 12 mg IT; day 1 
23  Cyclophosphamide 300-400 mg/m2 IV; day 1 
Vincristine 1 mg/m2 (max, 2 mg) IV; day 1 
Prednisone 1.5 mg/kg PO; days 1-5 
Low-intensity    
 INCTR 03-06 protocol 33  Cyclophosphamide 1200 mg/m2 IV; day 1 15-d cycles if ANC ≥1.0 × 109 /L and platelets ≥75 × 109/L 
Vincristine 1.4 mg/m2 (max, 2 mg) IV; day 1 3 cycles for low risk (single extra-abdominal site <10 cm) 
Methotrexate 75 mg/m2 IV; day 1 6 cycles for high risk (all others) 
Methotrexate 12 mg IT; days 1 and 8 
Cytarabine 50 mg IT; day 4 
With anthracyclines    
 CHOP 23  Cyclophosphamide 750 mg/m2 IV; day 1 21-d cycles × 6 cycles if ANC ≥1.0 × 109/L and platelets ≥75 × 109 /L 
Doxorubicin 40 mg/m2 IV; day 1 
Vincristine 1 mg/m2 (max, 2 mg) IV; day 1 
Prednisone 1.5 mg/kg PO; days 1-5 
Methotrexate 12 mg IT; day 1 
 JOOTRH protocol 35  Induction-consolidation  
 Cyclophosphamide 1200 mg/m2 IV; days 1, 8, 15, 22, 28, 35  
 Doxorubicin 60 mg/m2 IV; days 1, 22  
 Vincristine 1.5 mg/m2 IV; days 1, 8, 15, 22, 28, 35  
 Methotrexate 7.5 mg/m2 IT; days 1, 8, 15, 22  
 Prednisone PO tapering dose  
Maintenance Maintenance 
 Cyclophosphamide 300 mg/m2 IV; day 1  28-d cycles × 24 mo 
 Vincristine 1.5 mg/m2 IV; day 1  
 Malawi 2012-2014 protocol 36  Cyclophosphamide 40 mg/kg (max, 1.6 g) IV; days 1, 15, 28 Doxorubicin given for only stage III/IV 
Cyclophosphamide 60 mg/kg (max, 2.4 g) IV; day 8 
Doxorubicin 60 mg/m2 IV; days 15, 28 
Vincristine 1.5 mg/m2 (max, 2 mg) IV; days 1, 8, 15, 28 
Prednisone 60 mg/m2 PO; days 1-5 
Methotrexate 12.5 mg IT; day 1, 8, 15, 28 
With high-dose methotrexate    
 GFAOP 2001/2009 protocol 39  Induction Induction 
40   Cyclophosphamide 250 mg/m2 IV; days 1-3  15-d cycles × 2 cycles administered once (1) ANC ≥ 1.0 × 109 /L or ANC ≥ 0.5 × 109 /L and increasing; and (2) platelets ≥ 100 × 109 /L 
 Vincristine 1.5 mg/m2 (max, 2 mg) IV; day 1  Leucovorin given for 12 doses beginning 24 h after methotrexate 
 Methotrexate 1-3 g/m2 IV over 3 h; day 1  Alkaline hydration administered 2 h before and 2 h after methotrexate 
 Leucovorin 15 mg/m2 4× daily PO/IV; days 2-4  Methotrexate 1 g/m2 in 2001 protocol safely escalated to 3 g/m2 in 2009 protocol 
 Prednisone 60 mg/m2 PO; days 2-5  For stage IV with <70% blasts in bone marrow: cyclophosphamide 500 mg/m2 IV, days 1-2; vincristine 2 mg/m2 IV (max 2 mg) IV, Day 1 
 Methotrexate 12 mg IT; days 2 and 6 
Consolidation Consolidation 
 Methotrexate 1-3 g/m2 IV over 3 h; day 1  2 cycles administered once (1) ANC ≥ 1.0 × 109/L or ANC ≥ 0.5 × 109/L and increasing; and (2) platelets ≥ 100 × 109 /L 
 Leucovorin 15 mg/m2 4× daily PO/IV; days 2-4  Leucovorin given for 12 doses beginning 24 h after methotrexate 
 Cytarabine 50 mg/m2 2× daily SC; days 2-6  Alkaline hydration administered 2 h before and 2 h after methotrexate 
 Methotrexate 12 mg IT; day 2  Methotrexate 1 g/m2 in 2001 protocol safely escalated to 3 g/m2 in 2009 protocol 
 Cytarabine 50 mg IT; day 7 

ANC, absolute neutrophil count; max, maximum; PO, oral; SC, subcutaneous; IT, intrathecal.

*

Methotrexate IT was age-adjusted below 3 years in all protocols.

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