LALA

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Indication

Newly diagnosed acute lymphoblastic leukaemia L1 or L2 of the FAB classification age between 15 and 55 years

Risk Stratification

'Standard risk' ALL

  • All T-ALL except those not in remission after induction therapy
  • Non T-ALL with the following features:
    • CD10+/CD19+ or CD10-/CD19+/CD20+
    • no mixed or bi-phenotypic cases
    • not Ph1 or BCR/ABL positive, no t(4;11) or t(1;19) and 11q23 anomalies
    • with WCC < 30x109/L at diagnosis
    • minimal CNS involvement
    • CR reached after one induction

'High risk' ALL

  • Ph1 or BCR/ABL negative
  • T-ALL with no CR after one induction
  • Non T-ALL with one or more of the following criteria
    • CD10- and CD20-
    • WCC> 30x109/L at diagnosis
    • bi-phenotypic ALL
    • presence of t(4;11) or t(1;19) or other 11q23 anomalies
    • Initial CNS involvement
  • Philadelphia chromosome-positive ALL
    • Ph1 or BCR/ABL+ ALL patients

Important additional information

  • All patients receive the standard induction, but the consolidation arm is determined by their risk stratification
  • The choice of subsequent consolidation therapy is based on initial WCC, phenotype, cytogenics, molecular studies, presence of CNS disease and post induction remission status. Major complications during induction that limit further therapy or prolonged aplasia will affect subsequent choice of therapy.

Note: For patients who have Philadelphia chromosome or bcr-abl positive ALL, the use of Imatinib should be considered where appropriate.

  • All patients should have HLA typing upfront or as soon as possible in the course of treatment.

Regimen

Pre treatment evaluation and Fractionated chemotherapy in cases of high WBC

Neuromeningeal prophylaxis

Patients with CNS disease at diagnosis

Induction with either DNR or IDA

  • Idarubicin 9 mg/m2 1, 2, 3, 8 IV

or

  • Daunorubicin 30 mg/m2 1-3, 15, 16 IV
  • Vincristine 2 mg TD 1, 8, 15, 22 IV
  • Cyclophosphamide 750 mg/m2 1, 8 IV
  • Prednisone 60 mg/m2 1-7, 15-21 IV or PO

Restaging between D28 - 35 when recovered from Aplasia

Standard-risk ALL patients were randomly assigned on day 35 and received either an intensive consolidation chemotherapy combining mitoxantrone (MTZ) with intermediate-dose cytarabine (IDaraC), or a less intensive consolidation course combining CPM with cytarabine (araC), and mercaptopurine. Then, patients with standard-risk ALL followed a chemotherapy program for 2 years

On day 35, high-risk ALL patients were scheduled to receive a second course of intensive chemotherapy (consolidation or salvage), consisting of MTZ and IDaraC. Patients who did not reach a CR after that course were withdrawn from the protocol.

Consolidation

References

Thomas X, Boiron JM, Huguet F et al. . Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 2004 22(20):4075-4086.