MRC UKALL XII/ECOG E2993
MRC UKALL XII/ECOG E2993
Phase 1 of induction therapy (weeks 1-4)
Daunorubicin 60 mg/m2 IV on days 1, 8, 15, and 22
Vincristine 1.4 mg/m2 IV on days 1, 8, 15, and 22
L-asparaginase 10 000 IU IV or intramuscularly on days 17 to 28
Prednisone 60 mg/m2 PO in divided doses on days 1 to 28
Methotrexate 12.5 mg IT on day 15
Phase 2 of induction regardless of whether residual leukemia was in their marrow at the end of phase 1 (weeks 5-8)
Cyclophosphamide 650 mg/m2 IV on days 1, 15, and 29
Cytarabine 75 mg/m2 IV on days 1 to 4, 8 to 11, 15 to 18, and 22 to 25
6-Mercaptopurine (60 mg/m2) PO on days 1 to 28
Methotrexate 12.5 mg IT on days 1, 8, 15, and 22
Patients were evaluated for response at the end of each of the 2 phases of induction.
Those who achieved complete remission (CR) went on to the intensification and postremission consolidation.
Intensification therapy
High-dose methotrexate, 3 g/m2 IV given on days 1, 8, and 22 with standard leucovorin rescue
L-asparaginase 10 000 IU on days 2, 9, and 23
After induction therapy all patients younger than 50 years of age who had a human leukocyte antigen (HLA)compatible sibling were assigned to undergo allogeneic transplantation.
Patients who were Ph+ were offered a search for a matched unrelated donor if they did not have a histocompatible family donor.
Other patients either get autologous transplantation or consolidation/maintenance therapy.
Transplantation regimen (Allogenic or autologous)
Total body irradiation (TBI) for a total dose of 1320 cGy, given twice daily in 6 fractions of 220 cGy on day minus 6 to day minus 4
Etoposide 60 mg/kg IV on day minus 3
For Ph+ patients, 3 x 106 U alpha-interferon was given 3 times a week for 15 months post-transplantation, other patients recieve no maintenance
Consolidation/maintenance therapy (Non-transplant)
CNS prophylaxis
IT cytarabine, 50 mg, weekly for 4 weeks, together with 2400 cGy cranial irradiation
4 cycles of consolidation therapy followed by maintenance therapy
Cycle 1 of consolidation therapy
Cytarabine 75 mg/m2 IV on days 1 to 5
Eoposide 100 mg/m2 IV on days 1 to 5
Vincristine 1.4 mg/m2 IV on days 1, 8, 15, and 22
Dexamethasone 10 mg/m2 PO on days 1 to 28
Cycle 2 of consolidation therapy
Begin 4 weeks after cycle 1
Cytarabine 75 mg/m2 IV on days 1 to 5
Etoposide 100 mg/m2 IV on days 1 to 5
Cycle 3 of consolidation therapy
Begin 4 weeks after cycle 2
Daunorubicin 25 mg/m2 IV on days 1, 8, 15, and 22
Cyclophosphamide 650 mg/m2 IV on day 29
Cytarabine 75 mg/m2 IV on days 31 to 34 and 38 to 41
Thioguanine 60 mg/m2 PO on days 29 to 42
Cycle 4 of consolidation therapy (same as cycle 2)
Begin 8 weeks after the conclusion of cycle 3
Cytarabine 75 mg/m2 IV on days 1 to 5
Etoposide 100 mg/m2 IV on days 1 to 5
Maintenance therapy (total of 2.5 years from the start of intensification therapy)
Vincristine 1.4 mg/m2 IV every 3 months
Prednisone 60 mg/m2 PO for 5 days every 3 months
6-mercaptopurine 75 mg/m2 PO each day
Methotrexate 20 mg/m2 PO or IV once a week
50 mg intrathecal cytarabine was given on 4 occasions 3 months apart during maintenance therapy