Treatment of High Risk Adult Acute Lymphoblastic Leukemia (LAL-AR/2003)

• To evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels in HR Ph- adult ALL patients. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  

Drug: Vincristine
Vincristine (VCR): 1.5 mg/m2 (max 2 mg) IV d 1, 8, 15, 22 in induction VCR 2 mg, IV, d 1,8 in consolidation (cycle 1, 2)
Drug: Daunorubicin
Daunorubicin (DNR): 60 mg/m2 IV d 1, 8, 15, 22
Drug: Prednisone
Prednisone (PDN): 60 mg/m2/d IV or PO, d 1-28
Drug: Mitoxantrone
Mitoxantrone:12 mg/m2, IV d 15-17 in induction 12 mg/m2, IV,d 5 in cycle 2 consolidation
Drug: Cytosine Arabinoside
ARA-C 2,000 mg/m2/12h IV, d18,19 (4 doses) in induction
Drug: Dexamethasone
Dexamethasone 20 mg/m2,IV, d 1-5,10 mg/m2,IV, d 6 and 5 mg/m2,IV, d 7 in Consolidation (3 cycles)
Drug: Methotrexate (MTX)
Methotrexate (MTX)3 g/m2,IV, d1 (24h)in consolidation, cycles 1 and 2 MTX (15 mg/m2/wk, IM)in maintenance MTX 15 mg, IT
Drug: Cytarabine
Cytarabine 2g/m2/12h, IV d5 in cycle 1 consolidation Cytarabine 2g/m2/12h, IV d 1,2 in cycle 3 consolidation Cytarabine 30 mg, intrathecal
Drug: ASP
ASP 25,000 IU/m2, IV, d5 in consolidation (cycle 1, 2, 3)
Drug: Mercaptopurine
Mercaptopurine 100 mg/m2, PO, d 1-5 in consolidation
Drug: Teniposide
Teniposide 150 mg/m2, IV d 3,4 in consolidation cycle 3
Drug: Hydrocortisone
Hydrocortisone 20 mg, IT d 1, 28, 49, 77, 105, 175, 203, 231, 259,287, 311 intrathecal

HR ALL included one or more of the following baseline parameters: age 30-60 yr, WBC count >25x109/L and 11q23 or MLL rearrangements. Induction therapy included vincristine, prednisone and daunorubicin for 4 weeks. In pts with slow cytologic response to therapy (≥10% blasts in bone marrow assessed on d14) intensified induction with high dose ARA-C and mitoxantrone was administered. Early consolidation therapy included 3 cycles with rotating cytotoxic drugs including high-dose methotrexate, high-dose ARA-C and high-dose asparaginase. Pts. with slow cytologic response on d14 or MRD level >0.05% after consolidation were assigned to allogeneic SCT (related or unrelated) and those with standard cytologic response on d14 and MRD level <0.05% after consolidation received 3 additional cycles of delayed consolidation (identical to those of early consolidation) followed by maintenance therapy up to 2yr in CR.