Triple IT therapy (age-adjusted): days 1 and 22

VP-16 (100 mg/m2/day, IV): days 22-26

CPM (300 mg/m2/day, IV): days 22-26

MESNA (150 mg/m2/day, IV): days 22-26

G-CSF (5 μg/kg, SC): days 27-36 or until ANC > 1500 post nadir

ARA-C (3 g/m2, q12h, IV): days 43, 44

L-ASP (6000 IUnits/m2, IM): day 44
 
Maintenance

(8-week cycles)

Cycles 1–4
 MTX (5 g/m2 over 24 hours, IV): day 1

Leucovorin (75 mg/m2 at hour 36, IV; 15 mg/m2 IV or PO q6h x 6 doses)iii: days 2 and 3

Triple IT therapy (age-adjusted): days 1, 29

VCR (1.5 mg/m2, IV): days 1, 29

DEX (6 mg/m2/day PO): days 1-5; 29-33

6-MP (75 mg/m2/day, PO): days 8-28

Methotrexate (20 mg/m2/week, PO): days 8, 15, 22

VP-16 (100 mg/m2, IV): days 29-33

CPM (300 mg/m2, IV): days 29-33

MESNA IV days 29-33

G-CSF (5 μg/kg, SC): days 34-43
 
Maintenance

(8-week cycles)

Cycle 5
 Cranial irradiation (Block 5 only)

12 Gy in 8 fractions for all patients that are CNS1 and CNS2 at diagnosis

18 Gy in 10 fractions for patients that are CNS3 at diagnosis

VCR (1.5 mg/m2/day, IV): days 1, 29

DEX (6 mg/m2/day, PO): days 1-5; 29-33
6-MP (75 mg/m2/day, PO): days 11-56 (Withhold 6-MP during the 6-10 days of cranial irradiation beginning on day 1 of Cycle 5. Start 6-MP the 1st day after cranial irradiation completion.)
Methotrexate (20 mg/m2/week, PO): days 8, 15, 22, 29, 36, 43, 50
Maintenance
(8-week cycles)

Cycles 6-12
 VCR (1.5 mg/m2/day, IV): days 1, 29

DEX (6 mg/m2/day, PO): days 1-5; 29-33

6-MP (75 mg/m2/day, PO): days 1-56
Methotrexate (20 mg/m2/week, PO): days 1, 8, 15, 22, 29, 36, 43, 50
G-CSF = granulocyte colony stimulating factor, VP-16 = etoposide, MTX = methotrexate, IV = intravenous, SC = subcutaneous, IT = intrathecal, PO = oral, IM = intramuscular, ARA-C = cytarabine, CPM = cyclophosphamide, VCR = vincristine, DEX = dexamethasone, DAUN = daunorubicin, 6-MP = 6-mercaptopurine, E.Coli L-ASP = L-asparaginase, PEG-ASP = PEG asparaginase, MESNA= 2-mercaptoethane sulfonate sodium, iii= or until MTX level is < 0.1 µM, q6h = every 6 hours, Gy= Gray
Study AIT07 was a multicentre, open-label, randomised, phase II/III study that included 128 patients (1 to < 18 years) treated with imatinib in combination with chemotherapy. Safety data from this study seem to be in line with the safety profile of imatinib in Ph+ ALL patients.
Relapsed/refractory Ph+ ALL: When imatinib was used as single agent in patients with relapsed/refractory Ph+ ALL, it resulted, in the 53 out of 411 patients eva luable for response, in a haematological response rate of 30% (9% complete) and a major cytogenetic response rate of 23%. (Of note, out of the 411 patients, 353 were treated in an expanded access program without primary response data collected.) The median time to progression in the overall population of 411 patients with relapsed/refractory Ph+ ALL ranged from 2.6 to 3.1 months, and median overall survival in the 401 eva luable patients ranged from 4.9 to 9 months. The data was similar when re-analysed to include only those patients age 55 or older.
Clinical studies in MDS/MPD
Experience with Glivec in this indication is very limited and is based on haematological and cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit or increased survival. One open label, multicentre, phase II clinical trial (study B