Trial Information

Treatment Protocol For All Fragile Patients Ph' Negative Over 55 Years

Prephase (days -5 to -1) Dexamethasone 10 mg/m2 bolus day EV for 5 days (-5 to -1).
Supplementary treatment: hydration minimum 2000 ml / day. allopurinol 300 mg / day. gastric
protection (as center). daily monitoring of blood glucose daily monitoring of renal
function.

Intrathecal treatment (diagnosis and prophylactic / therapeutic) day -5: 12 mg were
administered intrathecal methotrexate. The morphological study of the CSF will be defining
initial CNS involvement by LAL. Although it is recommended immunophenotypic study of CSF,
the definition of CNS involvement by LAL (and its therapeutic consequences) based on
morphological observation of blasts in CSF cytocentrifuge.

Remission induction :

Tolerance prephase period can be used to establish the final indication of treatment
(standard protocol or frail patients). Day 0 is free of treatment and is considered as +1
the first day of induction.

Systemic treatment

- Vincristine (VCR) 1 mg (absolute dose) EV 1, 8, 15 and 22.

- Dexamethasone (DEX): 10 mg/m2 EV, IM or PO days 1-2, 8-9 days 15-16, 22-23.

Intrathecal chemotherapy

Triple therapy was administered with methotrexate (MTX), cytosine arabinoside (ARA-C) and
hydrocortisone, days 1, 8, 15 and 22 (five doses total prophylactic between prephase and
induction):

MTX 12 mg ARA-C 40 mg Dexamethasone 4 mg

If initial infiltration of the CNS is administered once every 72 hours until the
disappearance of blast cell morphology CSF (cytocentrifugation) in at least two consecutive
taps. Alternatively be administered liposomal cytarabine (DepoCyt) fortnightly if authorized
by the center or in the context of a clinical trial

Maintenance treatment of first year :

Maintenance during the first year will start after full recovery after induction and after
complete reassessment of the disease (including myelogram) and will last until one year from
the time of documentation of complete remission.

The basic treatment to include mercaptopurine 50 mg/m2 PO day and methotrexate 20 mg/m2 IM
weekly.

Once every 3 months will be added to maintenance treatment a "mini-reinduction" consisting

- VCR: 1 mg (absolute dose), i.v., day 1.

- Dexamethasone 40 mg / day, i.v. or p.o., days 1-2.

- Not considered more doses of triple intrathecal therapy. Reinduction only be practiced
during the first year after remission, so a total of 4 quarterly.

Maintenance of the second year:

After the first year of maintenance will perform a complete reassessment of the disease
(including myelogram) and if the patient remains in complete remission maintenance will
continue (without reinduction) until two years from the time of diagnosis.

The initial dose of mercaptopurine and methotrexate will be identical to the first year.
Must comply (by increases or decreases of 20% of the dose) to maintain the numbers of
neutrophil counts between 1.5 and 3x109/l and platelets above 100x109 / L