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Adult Acute Lymphocytic Leukemia

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LINKER REGIMEN >>>> DVPA (Induction)

INDUCTION
Daunorubicin 50 mg/m2 IVB days 1-3
Vincristine 2 mg IVB* days 1,8,15 & 22
Prednisone 20 mg/m2 PO q8h days 1-28*
Asparaginase 6000 IU/m2 IM days 17-28

*If patient is in remission, prednisone dose should be tapered.

If bone marrow has residual leukemia on day 14, give:
Daunorubicin 50 mg/m2 IVB day 15

If bone marrow has residual leukemia on day 28, give:
Daunorubicin 50 mg/m2 IVB days 29 & 30
Vincristine 2 mg IVB days 29 & 36
Prednisone 20 mg/m2 PO q8h days 29-42*
Asparaginase 6000 IU/m2 IM days 29-35

*Prednisone dose should be tapered.

CONSOLIDATION

Treatment A (cycles 1,3,5 & 7)
Daunorubicin 50 mg/m2 IVB days 1 & 2
Vincristine 2 mg IVB days 1 & 8
Prednisone 20 mg/m2 PO q8h days 1-14*
Asparaginase 12,000 IU/m2 IM days 2,4,7,9,11 & 14

*Prednisone dose should be tapered.

Treatment B (cycles 2,4,6 & 8)
Teniposide (VM26) 165 mg/m2 IVB days 1,4,8 & 11
Cytarabine 300 mg/m2 IVB days 1,4,8 & 11

Treatment C (cycle 9)
Methotrexate 690 mg/m2 CIV over 42 hours
Leucovorin 15 mg/m2 PO q6hX12 start at hour 42


Ref: Linker CL, et al: Blood 69:1242 (1987).

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Larsen Regimen



Ref:Larson et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood; 85(8):2025-37 1995

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Hyper-CVAD (MD-Anderson)



Ref:JCO 18, Issue 3 (February), 2000: 547

185 patients (91%) achieved complete remission (CR) & 12 (6%) died during induction therapy. Estimated 5-year survival & 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%).

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ALL-L3
CALGB 9251

CYCLE 1
 Cyclophosphamide 200 mg/m2/d IV days 1-5
 Prednisone 60 mg/m2/d orally days 1-7

CYCLES 2, 4, & 6
 Ifosfamide 800 mg/m2/d IV for 1 hr days 1-5
 Mesna 200 mg/m2/d IV at 0, 4, and 8 hrs after ifosfamide
 Methotrexate 150 mg/m2 IV for 30 minutes, then 1.35 g/m2 IV for 23.5 hrs (total dose: 1.5 g/m2)
 Leucovorin 50 mg/m2 IV 36 hrs after initiation of methotrexate, then 15 mg/m2 q 6 hr until methotrexate is < 10-8 M
 Vincristine 2 mg IV push day 1
 Cytarabine 150 mg/m2/d by continuous infusion on days 4 and 5
 Etoposide 80 mg/m2 IV over 1 hr on days 4 and 5
 Dexamethasone 10 mg/m2 orally days 1 through 5

Intrathecal Chemotherapy
 Methotrexate 15 mg on days 1 & 5
 Cytarabine 40 mg on days 1 & 5
 Hydrocortisone 50 mg on days 1 and 5


CYCLES 3, 5, & 7
 Cyclophosphamide 200 mg/m2/d on days 1-5
 Methotrexate 150 mg/m2 IV over 30 minutes, then 1.35 g/m2 IV over 23.5 hrs (total dose: 1.5 g/m2)
 Leucovorin 50 mg/m2 IV starting 36 hrs after initiation of methotrexate, then 15 mg/m2 q 6 hr until methotrexate < 10-8 M
 Vincristine 2 mg IV push
 Doxorubicin 25 mg/m2 IV bolus on days 4 and 5
 Dexamethasone 10 mg/m2 orally days 1-5

Intrathecal chemotherapy*
 Methotrexate 15 mg
 Cytarabine 40 mg
 Hydrocortisone 50 mg on days 1 and 5

CRANIAL IRRADIATION*
24 Gy administered for 12 fractions after chemotherapy for cycle 3 completed (after day 5, cycle 3) and before cycle 4 (before day 1, cycle 4)
*Because of neurotoxicity, this part of the regimen was modified.

REF= JCO 19, Issue 20 (October), 2001: 4014-4022, 2001.
N=24 L3 ALL & N=51(30 included in analysis) SNC 43 of 54 patients achieved CR (18 of 24 with ALL & 25 of 30 with SNC). 28 were alive & in continuous CR with a median follow-up of 5.1 years. Hematologic toxicity was profound, & nonhematologic toxicity was notable, with 10 of 75 patients treated developing significant neurologic toxicity consisting of transverse myelitis in five patients, CNS toxicity in 3, & severe peripheral neuropathy in 2. All patients who did not achieve CR died of the disease, & all recurrences occurred within 16 months of the end of treatment. Responses and toxicities were similar in the patients with both lymphoma & leukemia.
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ALL-L3
PATH: Cytoplasmic vacuolization. B-cell lineage, +surface immunoglobulin by flow cytometry, absence of Tdt,
CYTOLOGY: Balanced translocations involving the myc gene (chromosome 8) & one of the 3 loci involved with Ig synthesis, most commonly the heavy chain locus on chromosome 14.
CLINICAL: Propensity for CNS involvement.