Table 1.
Protocol Therapy
| Drug and Dosage | Day No. |
|---|---|
| Block 1 | |
| Vincristine, 1.5 mg/m2 IV | 1, 8, 15, and 22 |
| Prednisone, 40 mg/m2/d PO* | 1-29 |
| PEG-asparaginase, 2,500 U/m2 IM | 2, 9, 16, and 23 |
| Doxorubicin, 60 mg/m2 IV* | 1 |
| Imatinib mesylate, 340 mg/m2 PO† | 1-14 (Ph+) |
| Intrathecal cytarabine | 1 |
| Intrathecal methotrexate | 8 and 29 (CNS−) |
| Triple intrathecal therapy‡ | 8, 15, 22, and 29 (CNS+) |
| Block 2 | |
| Cyclophosphamide, 440 mg/m2 IV | 1-5 |
| Etoposide, 100 mg/m2 IV | 1-5 |
| Methotrexate, 5 g/m2 IV | 22 (pending blood count recovery) |
| Imatinib mesylate, 340 mg/m2 PO† | 1-14 (Ph+) |
| Intrathecal methotrexate | 1 and 22 (CNS−) |
| Triple intrathecal therapy | 1 and 22 (CNS+) |
| G-CSF, 5 mcg/kg SQ | 6 until ANC > 1,500/μL × 2 days |
| Block 3 | |
| Cytarabine, 3 g/m2 IV every 12 hours | 1, 2, 8, and 9 (Ph−) |
| L-asparaginase, 6,000 U/m2 IM | 2 and 9 at hour 42 after cytarabine (Ph−) |
| Cytarabine, 3 g/m2 IV every 12 hours† | 1, 2 (Ph+) |
| L-asparaginase, 6,000 U/m2 IM† | 2 (Ph+) |
| Imatinib mesylate, 340 mg/m2 PO† | 1-14 (Ph+) |
| G-CSF, 5 mcg/kg SQ | 10 until ANC > 1,500/μL × 2 days |
Abbreviations: IV, intravenous; PO, oral; IM, intramuscular; SQ, subcutaneous; Ph, Philadelphia chromosome; G-CSF, granulocyte colony-stimulating factor; LP, lumbar puncture.
The first 21 patients received idarubicin 10 mg/m2 IV every day on days 1 and 2, and dexamethasone 10 mg/m2 PO on days 1 to 14 (taper days 11 to 14) during block 1. The protocol was subsequently amended for toxicity and all remaining patients received doxorubicin and prednisone as shown above.
Ph+ only. Ph+ patients did not receive day 8 or 9 cytarabine or day 9 L-asparaginase during block 3.
Triple intrathecal therapy (methotrexate, cytarabine, and hydrocortisone) was continued weekly beyond four doses until two successive LPs were free of blasts. All intrathecal medications were dosed based on age.