AIEOP-BFM ALL 2000 treatment phases for AIEOP HR patients
| Drug/administration route . | Daily dose (mg/m2 ) . | Day . |
|---|---|---|
| Prephase | ||
| Prednisone/po-IV | 60 | 1-7 |
| MTX/IT | By age* | 1 |
| Induction: protocol IA | ||
| Vincristine/IV | 1.5 (max 2 mg) | 8, 15, 22, 29 |
| Prednisone/po-IV (®†) | 60 | 8-28 then tapered |
| or Dexamethasone/po-IV (®†) | 10 | 8-28 then tapered |
| Daunorubicin/IV | 30 | 8, 15, 22, 29 |
| l-Asparaginase/IM | 5000 IU/m2 | 12, 15, 18, 21, 24, 27, 30, 33 |
| MTX/IT | By age* | 1, 15, 29|| |
| Consolidation: protocol IB | ||
| Cyclophosphamide/IV | 1000 | 36, 64 |
| Mercaptopurine/po | 60 | 36-63 |
| Cytarabine/IV-SC | 75 | 38-41, 45-48, 52-55, 59-62 |
| MTX/IT | By age* | 38, 52 |
| HR block 1 | ||
| Dexamethasone/po-IV | 20 | 1-5 |
| Vincristine/IV | 1.5 (max 2 mg) | 1, 6 |
| HD Cytarabine/IV | 2000 × 2 | 5 |
| MTX/IV | 5000 | 1 |
| Leucovorin rescue‡ | 15 mg/m2/dose | 42, 48, 54 h after start HD-MTX |
| Cyclophosphamide/IV | 200 (q12h × 5) | 2-4 |
| l-Asparaginase/IM | 10 000 IU/m2 | 6 |
| MTX/IT | By age* | 1 |
| HR block 2 | ||
| Dexamethasone/po-IV | 20 | 1-5 |
| Vindesine/IV | 3 | 1, 6 |
| Daunorubicin/IV | 30 | 5 |
| MTX/IV | 5000 | 1 |
| Leucovorin rescue‡ | 15 mg/m2/dose | 42, 48, 54 h after start HD-MTX |
| Ifosphamide/IV | 800 (q12h × 5) | 2-4 |
| l-Asparaginase/IM | 10 000 IU/m2 | 6 |
| MTX/IT | By age* | 1 |
| HR block 3 | ||
| Dexamethasone/po-IV | 20 | 1-5 |
| HD Cytarabine/IV | 2000 (q 12 h × 4) | 1, 2 |
| Etoposide/IV | 100 (q 12 h × 5) | 3-5 |
| l-Asparaginase/IM | 10 000 IU/m2 | 6 |
| MTX/IT | By age* | 5 |
| Reinduction (protocol II) | ||
| Dexamethasone/po- IV§ | 10 | 1-21 then tapered |
| Vincristine/IV | 1.5 (max 2 mg) | 8, 15, 22, 29 |
| Doxorubicin/IV | 25 | 8, 15, 22, 29 |
| l-Asparaginase/IM | 10 000 IU/m2 | 8, 11, 15, 18 |
| 6-Thioguanine/po | 60 | 36-49 |
| Cyclophosphamide/IV | 1000 | 36 |
| Cytarabine/IV-SC | 75 | 38-41, 45-47 |
| MTX/IT | By age* | 38, 45 |
| Cranial irradiation¶ | By age | |
| Reinduction (protocol III) | ||
| Dexamethasone/po-IV | 10 | 1-14 then tapered |
| Vincristine/ IV | 1.5 (max 2 mg) | 1, 8 |
| Doxorubicin/IV | 30 | 1, 8 |
| l-Asparaginase/IM | 10 000 IU/m2 | 1, 4, 8, 11 |
| 6-Thioguanine/po | 60 | 15-28 |
| Cyclophosphamide/IV | 500 | 15 |
| Cytarabine/IV-SC | 75 | 17-20, 24-27 |
| MTX/IT | By age* | 17, 24 |
| Cranial irradiation¶ | By age | |
| Interim maintenance | ||
| Mercaptopurine/po | 50 | Daily |
| MTX/po | 20 | Weekly |
| Continuation phase‡ | ||
| Mercaptopurine/po | 50# | Daily |
| MTX/po | 20# | Weekly |
| Drug/administration route . | Daily dose (mg/m2 ) . | Day . |
|---|---|---|
| Prephase | ||
| Prednisone/po-IV | 60 | 1-7 |
| MTX/IT | By age* | 1 |
| Induction: protocol IA | ||
| Vincristine/IV | 1.5 (max 2 mg) | 8, 15, 22, 29 |
| Prednisone/po-IV (®†) | 60 | 8-28 then tapered |
| or Dexamethasone/po-IV (®†) | 10 | 8-28 then tapered |
| Daunorubicin/IV | 30 | 8, 15, 22, 29 |
| l-Asparaginase/IM | 5000 IU/m2 | 12, 15, 18, 21, 24, 27, 30, 33 |
| MTX/IT | By age* | 1, 15, 29|| |
| Consolidation: protocol IB | ||
| Cyclophosphamide/IV | 1000 | 36, 64 |
| Mercaptopurine/po | 60 | 36-63 |
| Cytarabine/IV-SC | 75 | 38-41, 45-48, 52-55, 59-62 |
| MTX/IT | By age* | 38, 52 |
| HR block 1 | ||
| Dexamethasone/po-IV | 20 | 1-5 |
| Vincristine/IV | 1.5 (max 2 mg) | 1, 6 |
| HD Cytarabine/IV | 2000 × 2 | 5 |
| MTX/IV | 5000 | 1 |
| Leucovorin rescue‡ | 15 mg/m2/dose | 42, 48, 54 h after start HD-MTX |
| Cyclophosphamide/IV | 200 (q12h × 5) | 2-4 |
| l-Asparaginase/IM | 10 000 IU/m2 | 6 |
| MTX/IT | By age* | 1 |
| HR block 2 | ||
| Dexamethasone/po-IV | 20 | 1-5 |
| Vindesine/IV | 3 | 1, 6 |
| Daunorubicin/IV | 30 | 5 |
| MTX/IV | 5000 | 1 |
| Leucovorin rescue‡ | 15 mg/m2/dose | 42, 48, 54 h after start HD-MTX |
| Ifosphamide/IV | 800 (q12h × 5) | 2-4 |
| l-Asparaginase/IM | 10 000 IU/m2 | 6 |
| MTX/IT | By age* | 1 |
| HR block 3 | ||
| Dexamethasone/po-IV | 20 | 1-5 |
| HD Cytarabine/IV | 2000 (q 12 h × 4) | 1, 2 |
| Etoposide/IV | 100 (q 12 h × 5) | 3-5 |
| l-Asparaginase/IM | 10 000 IU/m2 | 6 |
| MTX/IT | By age* | 5 |
| Reinduction (protocol II) | ||
| Dexamethasone/po- IV§ | 10 | 1-21 then tapered |
| Vincristine/IV | 1.5 (max 2 mg) | 8, 15, 22, 29 |
| Doxorubicin/IV | 25 | 8, 15, 22, 29 |
| l-Asparaginase/IM | 10 000 IU/m2 | 8, 11, 15, 18 |
| 6-Thioguanine/po | 60 | 36-49 |
| Cyclophosphamide/IV | 1000 | 36 |
| Cytarabine/IV-SC | 75 | 38-41, 45-47 |
| MTX/IT | By age* | 38, 45 |
| Cranial irradiation¶ | By age | |
| Reinduction (protocol III) | ||
| Dexamethasone/po-IV | 10 | 1-14 then tapered |
| Vincristine/ IV | 1.5 (max 2 mg) | 1, 8 |
| Doxorubicin/IV | 30 | 1, 8 |
| l-Asparaginase/IM | 10 000 IU/m2 | 1, 4, 8, 11 |
| 6-Thioguanine/po | 60 | 15-28 |
| Cyclophosphamide/IV | 500 | 15 |
| Cytarabine/IV-SC | 75 | 17-20, 24-27 |
| MTX/IT | By age* | 17, 24 |
| Cranial irradiation¶ | By age | |
| Interim maintenance | ||
| Mercaptopurine/po | 50 | Daily |
| MTX/po | 20 | Weekly |
| Continuation phase‡ | ||
| Mercaptopurine/po | 50# | Daily |
| MTX/po | 20# | Weekly |
IM, intramuscular; IT, intrathecal; po, by mouth; Pred, prednisone; SC, subcutaneous.
Age-adjusted doses of intrathecal MTX: ≥1 and <2 y: 8 mg; ≥2 and <3 y: 10 mg; ≥3 y: 12 mg
According to first randomization (®).
Leucovorin rescue: 7.5-mg/m2 dose for levorotatory compound given at hours 42, 48, and 54 for HD-MTX 5 g/m2.
Dexamethasone in protocol II in HR patients aged ≥10 y: 10 mg/m2 days 1 to 7 and 15 to 21.
Patients with initial CNS involvement received additional intrathecal therapy on day 8 and 22 during induction protocol IA.
Cranial radiotherapy was administered after the first reinduction phase (during the interim phase) at the following dose: age 1 to 2 y, 12 Gy (preventive) or 18 Gy (therapeutic for CNS involvement at diagnosis); age ≥2y, 18 Gy (preventive) or 24 Gy (therapeutic for CNS involvement at diagnosis).
Doses were adjusted to WBC count (target range, 2000-3000 per µL).