== Regimen ==
'''For Medium and High Risk Patients'''<br>
Standard risk patients are, by definition, paediatric patients and are not included in the protocol as it
appears here (See Risk Groups Below)
=== Induction therapy Phase 1 - part 1 ===
Methotrexate 12 mg (12 mg) IT INTRATHECAL Day 1 , 12, (18, 27 CNS DISEASE AT DIAGNOSIS ONLY),
33
Prednisolone 60 mg/m² orally daily days 1 to day 29
Vincristine 1.5 mg/m² IVI Days 8,15,22,29
Daunorubicin 30 mg/m² IVI Days 8,15,22,29
L-asparaginase 5000 units/m² IVI over 60 minutes (ensure test dose has been given) given) Days
12,15,18,21,24,27,30,33
=== Induction therapy, Phase 1 - part 2 ===
6-Mercaptopurine 60 mg/m² orally daily from day 36 to day 63 (28 days total)
Cyclophosphamide 1000 mg/m² by IV infusion Day 36, 64
Mesna 400 mg/m² by IV infusion hours 0, 4 and 8 post cyclophosphamide
Cytarabine 75 mg/m² by IV infusion daily days 38 to 41, 45 to 48, 52 to 55, 59 to 62
Methotrexate 12 mg IT INTRATHECAL Days 45, 59
=== MCA Consolidation ===
Commence this cycle 2 weeks post the completion of Part 1, phase 2<br>
Requirements for commencing consolidation include good general condition, no severe infections,
normal creatinine clearance, ALT and AST <5x upper limit of normal, bilirubin <3x upper limit of normal
and adequate neutrophil/platelet recovery (WBC >1.5, neutrophils > 0.5 and platelets > 50).<br>
Do not administer methotrexate in the absence of normal creatinine and creatinine clearance. <br>
6-Mercaptopurine is to be temporarily ceased if cytarabine if postponed and further doses to be given at
the end of the cycle.<br>
6-Mercaptopurine 25 mg/m² orally days 1 to 56
Methotrexate 500 mg/m² IVI over 30 minutes days 8, 22, 36, 50
Methotrexate 4500 mg/m² by IV infusion over 23.5 hours days 8, 22, 36, 50
Methotrexate 12 mg IT INTRATHECAL days 8, 22, 36, 50
Leucovorin (Calcium folinate) 15 mg/m² IVI at hour 42 post commencement of MTX infusion;
continue Q6H until MTX level <0.25micromol/L days 9, 23, 37, 51
Cytarabine 200 mg/m² as a continuous IV infusion over 24 hours (commence as soon as MTX has
completed) Days 9, 23, 37, 51
=== Protocol 2, part 1 ===
Begin this cycle 2 weeks after completing BFM MCA consolidation and WBC >2.5 x 109/L, ANC >1.0 x
109/L and platelets >100 x 109/L <br>
Vincristine is capped at 2mg<br>
Dexamethasone 10 mg/m² orally days 1 to 21
Methotrexate 12 mg (12 mg) IT ONLY FOR PATIENTS WITH CNS DOSEASE AT DIAGNOSIS days 1,
18
Vincristine 1.5 mg/m² IVI Days 8,15,22,29
Doxorubicin 30 mg/m² IVI Days 8,15,22,29
L-asparaginase 10000 units/m² IVI over 1 to 2 hours Days 8,11,15,18
=== Protocol 2, part 2 ===
Commence when WBC >2.0 x 109/L neutrophils >0.5 x 109/L and platelets >50 x 109/L and creatinine is
normal<br>
Cytarabine blocks should commence when WBC > 0.5 x 109/L and platelets > 30 x 109/L<br>
6-Thioguanine (6-TG) is to be temporarily ceased if cytarabine if postponed and further doses to be
given at the end of the cycle to total dose of 840mg/m2<br>
Cranial irradiation usually commences day 38. Doses as follows:<br>
o 18Gy if CNS involvement or
o 12Gy as prophylactic therapy for T cell ALL, high risk patients and planned allogeneic stem cell
transplant
Thioguanine 60 mg/m² orally daily from day 36 to 49 (14 days total)
Cyclophosphamide 1000 mg/m² by IV infusion over 1 hour Days 36
Mesna 400 mg/m² by IV infusion hour 0, 4 and 8 of cyclophosphamide infusion
Methotrexate 12 mg (12 mg) IT INTRATHECAL Day 38, 45
Cytarabine 75 mg/m² by IV infusion days 38 to 41, 45 to 48 (over 30 to 60 minutes each day)
=== Standard maintenance therapy ===
PCP prophylaxis must be given throughout this consolidation treatment<br>
Usually commences 2 weeks after conclusion of Protocol II depending on WBC and patient’s condition
<br>
6-Mercaptopurine 50 mg/m² orally day 1 to day 70
Methotrexate 20 mg/m² orally weekly for a total of ten doses
No of cycles: 6 cycles with a 1 week break between cycles - i.e. 104 weeks in total
== Risk Groups ==
Standard risk group
* Leukaemic cells < 1000micromol/L in the peripheral blood on day 8 after 7 day prednisone pre-phase
* WBC <20 000 micromol/L and age >1 <6 years
* A complete remission on day 33 (M1-marrow)
* No translocation t(9;22) or BCR/ABL recombination
* No translocation t(4;11) or MLL/AF4 recombination
* No T-immunology
* All six criteria must be met
Medium risk group
* Leukaemic cells < 1000micromol/L in the peripheral blood on day 8 after 7 day prednisone pre-phase
* Complete remission on day 33 (M1-marrow)
* No translocation t(9;22) or BCR/ABL recombination
* No translocation t(4;11) or MLL/AF4 recombination
* All 4 criteria must be met as well as at least one of the following
* Leukocytes > 20000 micromol/L
* Age < 1 year
* Age > 6 years
High risk group
* 1000micromol/L leukaemic cells in the peripheral blood on day 8
* No complete remission on day 33
* Translocation t(9;22) or BCR/ABL recombination
* Translocation t(4;11) or MLL/AF4 recombination
* Each criterion alone qualifies as high risk regardless of age and WBC
== Dose Modifications ==
=== Hepatic dysfunction ===
Daunorubicin & Doxorubicin
Bilirubin 20-50 micromols/L dose at 50%
Bilirubin > 50 micromol/L dose at 25% of total dose.
L-asparaginase - use caution
Vincristine Bilirubin > 50micromol/L dose at 50%
=== Renal impairment ===
Cyclophosphamide
GFR (mL/min) Dose (% of total dose to be given)
> 50 100
<50 omit
Do not administer methotrexate if CrCl <50ml/min
=== Peripheral neuropathy ===
Omit vincristine if grade 2 or above neuropathy
