Treatment protocols3-150 for standard- and intermediate-risk patients in ALL-BFM 86 and ALL-BFM 90
| Drug . | ALL-BFM 86 . | ALL-BFM 90 . | Glutathione S-Transferase Substrate . | ||
|---|---|---|---|---|---|
| Dose . | Administered on Days . | Dose . | Administered on Days . | ||
| Induction | |||||
| Prednisone (orally) | 60 mg/m2/d | 1-28 | 60 mg/m2/d | 1-28 | Potential22 25 |
| Vincristine (IV) | 1.5 mg/m2/d (max 2 mg) | 8, 15, 22, 29 | 1.5 mg/m2/d (max 2 mg) | 8, 15, 22, 29 | |
| Daunorubicin (IV) | 40 mg/m2/d | 8, 15, 22, 29 | 30 mg/m2/d | 8, 15, 22, 29 | Indirect22,26 27 |
| L-Asparaginase (IV) | 10 000 IU/m2/d | 19, 22, 25, 28, 31, 34, 37, 40 | 10 000 IU/m2/d | 12, 15, 18, 21, 24, 27, 30, 33 | |
| Cyclophosphamide (IV) | 1000 mg/m2/d | 43, 71 | 1000 mg/m2/d | 36, 64 | Yes22 24 |
| Cytarabine (IV) | 75 mg/m2/d | 45-48, 52-55, 59-62, 66-69 | 75 mg/m2/d | 38-41, 45-48, 52-55, 59-62 | |
| 6-Mercaptopurine (orally) | 60 mg/m2/d | 43-70 | 60 mg/m2/d | 36-64 | |
| Methotrexate (IT) | 12 mg/d | 1, 45, 59 | 12 mg/d | 1, 15, 29, 45, 59 | |
| Consolidation | |||||
| 6-Mercaptopurine (orally) | 25 mg/m2/d | 1-56 | 25 mg/m2/d | 1-56 | |
| Methotrexate (24-h INF) | 5 g/m2/d | 8, 22, 36, 50 | 5 g/m2/d | 8, 22, 36, 50 | |
| Methotrexate (IT) | 12 mg/d | 8, 22, 36, 50 | 12 mg/d | 8, 2, 36, 50 | |
| L-Asparaginase (IM) | — | — | 25 000 IU/m2/d | 10, 24, 38, 52 | |
| Reinduction | |||||
| Dexamethasone (orally) | 10 mg/m2/d | 1-21 | 10 mg/m2/d | 1-21 | Yes22 25 |
| Vincristine (IV) | 1.5 mg/m2/d (max 2 mg) | 8, 15, 22, 29 | 1.5 mg/m2/d (max 2 mg) | 8, 15, 22, 29 | |
| Doxorubicin (IV) | 30 mg/m2/d | 8, 15, 22, 29 | 30 mg/m2/d | 8, 15, 22, 29 | Indirect22,26 27 |
| L-Asparaginase (IV) | 10 000 IU/m2/d | 8, 11, 15, 18 | 10 000 IU/m2/d | 8, 11, 15, 18 | |
| Cyclophosphamide (IV) | 1000 mg/m2/d | 36 | 1000 mg/m2/d | 36 | Yes22 24 |
| Cytarabine (IV) | 75 mg/m2/d | 38-41, 45-48 | 75 mg/m2/d | 38-41, 45-48 | |
| 6-Thioguanine (orally) | 60 mg/m2/d | 36-49 | 60 mg/m2/d | 36-49 | |
| Methotrexate (IT) | 12 mg/d | 38, 45 | 12 mg/d | 38, 45 | |
| Late intensification3-151 | |||||
| Prednisone (orally) | 100 mg/m2/d | 1-7, 15-21 | — | — | Potential22 25 |
| Vindesine (IV) | 3 mg/m2/d (max 5 mg) | 1, 8, 15, 22 | — | — | |
| Teniposide (IV) | 150 mg/m2/d | 1, 8, 15, 22 | — | — | |
| Ifosfamide (IV) | 1000 mg/m2/12 h | 1, 2 | — | — | Yes48 49 |
| Cytarabine (3-h INF) | 2000 mg/m2/12 h | 15, 16 | — | — | |
| Drug . | ALL-BFM 86 . | ALL-BFM 90 . | Glutathione S-Transferase Substrate . | ||
|---|---|---|---|---|---|
| Dose . | Administered on Days . | Dose . | Administered on Days . | ||
| Induction | |||||
| Prednisone (orally) | 60 mg/m2/d | 1-28 | 60 mg/m2/d | 1-28 | Potential22 25 |
| Vincristine (IV) | 1.5 mg/m2/d (max 2 mg) | 8, 15, 22, 29 | 1.5 mg/m2/d (max 2 mg) | 8, 15, 22, 29 | |
| Daunorubicin (IV) | 40 mg/m2/d | 8, 15, 22, 29 | 30 mg/m2/d | 8, 15, 22, 29 | Indirect22,26 27 |
| L-Asparaginase (IV) | 10 000 IU/m2/d | 19, 22, 25, 28, 31, 34, 37, 40 | 10 000 IU/m2/d | 12, 15, 18, 21, 24, 27, 30, 33 | |
| Cyclophosphamide (IV) | 1000 mg/m2/d | 43, 71 | 1000 mg/m2/d | 36, 64 | Yes22 24 |
| Cytarabine (IV) | 75 mg/m2/d | 45-48, 52-55, 59-62, 66-69 | 75 mg/m2/d | 38-41, 45-48, 52-55, 59-62 | |
| 6-Mercaptopurine (orally) | 60 mg/m2/d | 43-70 | 60 mg/m2/d | 36-64 | |
| Methotrexate (IT) | 12 mg/d | 1, 45, 59 | 12 mg/d | 1, 15, 29, 45, 59 | |
| Consolidation | |||||
| 6-Mercaptopurine (orally) | 25 mg/m2/d | 1-56 | 25 mg/m2/d | 1-56 | |
| Methotrexate (24-h INF) | 5 g/m2/d | 8, 22, 36, 50 | 5 g/m2/d | 8, 22, 36, 50 | |
| Methotrexate (IT) | 12 mg/d | 8, 22, 36, 50 | 12 mg/d | 8, 2, 36, 50 | |
| L-Asparaginase (IM) | — | — | 25 000 IU/m2/d | 10, 24, 38, 52 | |
| Reinduction | |||||
| Dexamethasone (orally) | 10 mg/m2/d | 1-21 | 10 mg/m2/d | 1-21 | Yes22 25 |
| Vincristine (IV) | 1.5 mg/m2/d (max 2 mg) | 8, 15, 22, 29 | 1.5 mg/m2/d (max 2 mg) | 8, 15, 22, 29 | |
| Doxorubicin (IV) | 30 mg/m2/d | 8, 15, 22, 29 | 30 mg/m2/d | 8, 15, 22, 29 | Indirect22,26 27 |
| L-Asparaginase (IV) | 10 000 IU/m2/d | 8, 11, 15, 18 | 10 000 IU/m2/d | 8, 11, 15, 18 | |
| Cyclophosphamide (IV) | 1000 mg/m2/d | 36 | 1000 mg/m2/d | 36 | Yes22 24 |
| Cytarabine (IV) | 75 mg/m2/d | 38-41, 45-48 | 75 mg/m2/d | 38-41, 45-48 | |
| 6-Thioguanine (orally) | 60 mg/m2/d | 36-49 | 60 mg/m2/d | 36-49 | |
| Methotrexate (IT) | 12 mg/d | 38, 45 | 12 mg/d | 38, 45 | |
| Late intensification3-151 | |||||
| Prednisone (orally) | 100 mg/m2/d | 1-7, 15-21 | — | — | Potential22 25 |
| Vindesine (IV) | 3 mg/m2/d (max 5 mg) | 1, 8, 15, 22 | — | — | |
| Teniposide (IV) | 150 mg/m2/d | 1, 8, 15, 22 | — | — | |
| Ifosfamide (IV) | 1000 mg/m2/12 h | 1, 2 | — | — | Yes48 49 |
| Cytarabine (3-h INF) | 2000 mg/m2/12 h | 15, 16 | — | — | |
All patients in our study received maintenance therapy with oral 6-mercaptopurine (50 mg/m2/d) and methotrexate (20 mg/m2/wk) for 24 mo.
Patients in the intermediate-risk group of ALL-BFM 86 were randomized to either receive late intensification after reinduction or not to receive it.
IV: intravenously; IT: intrathecally, doses were adjusted for children <3 y; INF: intravenous infusion; IM: intramuscularly, only given in ALL-BFM 90 where patients were randomized to consolidation protocols with or without IM L-Asparaginase.