Treatment schedule for high-risk patients
| . | mg/m2 . | Day . |
|---|---|---|
| Induction (protocol I) | ||
| Protocol Ia | ||
| Vincristine | 1.5 | 8, 15, 22, 29 |
| Prednisone | 60 | 1-28 |
| Daunorubicin | 30 | 8, 15, 22, 29 |
| L-Asparaginase | 10 000† | 19, 22, 26, 28, 31, 34, 37, 40 |
| Protocol Ib | ||
| Cyclophosphamide | 1 000 | 43, 71 |
| 6-Mercaptopurine | 60 | 43-70 |
| Cytarabine | 75 | 45-48, 52-55, 59-62, 66-69 |
| Intrathecal methotrexate | By age‡ | 1 |
| Triple intrathecal therapy | By age‡ | 15, 29, 45, 591-154 |
| Consolidation | ||
| Block 1 | ||
| Vincristine | 1.5 | 1, 8 |
| Dexamethasone | 20 | 1-5 |
| 6-Mercaptopurine | 100 | 1-5 |
| Methotrexate | 5 000 | 1 |
| Leucovorin (levo) | 7.5 | + 36, 42, 48 h after methotrexate infusion start |
| Cytarabine | 2 000 q12h | 5 |
| L-Asparaginase | 25 000† | 6 |
| Triple intrathecal therapy | By age‡ | 1 |
| Block 2 | See legend | |
| Vindesine | 3 000 | 1 |
| Dexamethasone | 10 | 1-5 |
| 6-Thioguanine | 100 | 1-5 |
| Methotrexate | 5 000 | 1 |
| Leucovorin (levo) | 7.5 | + 36, 42, 48 h after methotrexate infusion start |
| Daunorubicin | 50 | 5 |
| L-Asparaginase | 25 000† | 5 |
| Cyclophosphamide | 150 | 5 |
| Triple intrathecal therapy | By age‡ | 1 |
| Block 3 | ||
| Dexamethasone | 20 | 1-5 |
| Cytarabine | 2 000 q12h | 1-2 |
| L-Asparaginase | 25 000† | 6 |
| Etoposide | 150 | 3-5 |
| Triple intrathecal therapy | By age‡ | 5 |
| Reinduction (protocol II)* | ||
| Dexamethasone | 10 | 1-21 |
| Vincristine | 1.5 | 8, 15, 22, 29 |
| Doxorubicin | 30 | 8, 15, 22, 29 |
| L-Asparaginase | Random | |
| 6-Thioguanine | 60 | 36-49 |
| Cyclophosphamide | 1 000 | 36 |
| Cytarabine | 75 | 38-41, 45-48 |
| Triple intrathecal therapy | By age‡ | 38, 45 (only during first reinduction) |
| Cranial radiotherapy | Based on age and CNS status1-153 | |
| Maintenance | ||
| 6-Mercaptopurine | 50 | 1-21 |
| Methotrexate (intramuscular) | 20 | 1, 8, 15 |
| Vincristine | 1.5 | 22 |
| Prednisone | 40 | 22-26 |
| . | mg/m2 . | Day . |
|---|---|---|
| Induction (protocol I) | ||
| Protocol Ia | ||
| Vincristine | 1.5 | 8, 15, 22, 29 |
| Prednisone | 60 | 1-28 |
| Daunorubicin | 30 | 8, 15, 22, 29 |
| L-Asparaginase | 10 000† | 19, 22, 26, 28, 31, 34, 37, 40 |
| Protocol Ib | ||
| Cyclophosphamide | 1 000 | 43, 71 |
| 6-Mercaptopurine | 60 | 43-70 |
| Cytarabine | 75 | 45-48, 52-55, 59-62, 66-69 |
| Intrathecal methotrexate | By age‡ | 1 |
| Triple intrathecal therapy | By age‡ | 15, 29, 45, 591-154 |
| Consolidation | ||
| Block 1 | ||
| Vincristine | 1.5 | 1, 8 |
| Dexamethasone | 20 | 1-5 |
| 6-Mercaptopurine | 100 | 1-5 |
| Methotrexate | 5 000 | 1 |
| Leucovorin (levo) | 7.5 | + 36, 42, 48 h after methotrexate infusion start |
| Cytarabine | 2 000 q12h | 5 |
| L-Asparaginase | 25 000† | 6 |
| Triple intrathecal therapy | By age‡ | 1 |
| Block 2 | See legend | |
| Vindesine | 3 000 | 1 |
| Dexamethasone | 10 | 1-5 |
| 6-Thioguanine | 100 | 1-5 |
| Methotrexate | 5 000 | 1 |
| Leucovorin (levo) | 7.5 | + 36, 42, 48 h after methotrexate infusion start |
| Daunorubicin | 50 | 5 |
| L-Asparaginase | 25 000† | 5 |
| Cyclophosphamide | 150 | 5 |
| Triple intrathecal therapy | By age‡ | 1 |
| Block 3 | ||
| Dexamethasone | 20 | 1-5 |
| Cytarabine | 2 000 q12h | 1-2 |
| L-Asparaginase | 25 000† | 6 |
| Etoposide | 150 | 3-5 |
| Triple intrathecal therapy | By age‡ | 5 |
| Reinduction (protocol II)* | ||
| Dexamethasone | 10 | 1-21 |
| Vincristine | 1.5 | 8, 15, 22, 29 |
| Doxorubicin | 30 | 8, 15, 22, 29 |
| L-Asparaginase | Random | |
| 6-Thioguanine | 60 | 36-49 |
| Cyclophosphamide | 1 000 | 36 |
| Cytarabine | 75 | 38-41, 45-48 |
| Triple intrathecal therapy | By age‡ | 38, 45 (only during first reinduction) |
| Cranial radiotherapy | Based on age and CNS status1-153 | |
| Maintenance | ||
| 6-Mercaptopurine | 50 | 1-21 |
| Methotrexate (intramuscular) | 20 | 1, 8, 15 |
| Vincristine | 1.5 | 22 |
| Prednisone | 40 | 22-26 |
Protocol II was repeated after a 6-week interim maintenance phase during which the patients received 6-mercaptopurine and methotrexate as in the maintenance described below (§).
IU/m2.
Age-adjusted doses of triple intrathecal therapy were for methotrexate, cytarabine, and prednisolone, respectively, as follows: younger than 1 year, 6/16/4 mg; 1 or older but younger than 2 years, 8/20/6 mg; 2 or older but younger than 3 years, 10/26/8 mg; 3 years or older, 12/30/10 mg.
Cranial radiotherapy was administered once during interim maintenance at the following doses: age 1-2 years, 12 Gy (18 Gy if CNS+ at diagnosis); age 2 years and older, 18 Gy (24 if CNS+); for high-risk patients younger than 1 year, extended triple intrathecal therapy during maintenance was substituted for cranial radiotherapy. Then tapered.
Patients with CNS leukemia had additional triple intrathecal therapy on days 8 and 22.