Medical Research Council Working Party on Leukaemia in Children UK National Lymphoblastic Leukaemia (ALL) Trial

OBJECTIVES:

• Compare the effects of oral prednisolone vs oral dexamethasone on remission rate, event-free survival, and overall survival of children with acute lymphoblastic leukemia.
• Compare the effect of oral mercaptopurine (MP) vs oral thioguanine (TG) on remission rate, event-free survival, and overall survival of this patient population.
• Assess the effect of a schedule concentrating on tight control of maintenance therapy, compensating where necessary for constitutional drug resistance and avoiding poor physician or patient compliance, on event-free survival of these patients.
• Compare the pharmacokinetics of MP and TG in these patients.
• Collect data on the presence or absence of minimal residual disease in serial bone marrow samples to assess its clinical importance.

OUTLINE: This is a randomized, multicenter study. Patients are randomized twice during the study: prednisolone vs dexamethasone and mercaptopurine vs thioguanine. Patients are initially stratified according to risk status (standard vs intermediate vs high). Patients are stratified at the second randomization according to gender, age (under 2 years vs 2 to 9 years vs over 9 years), WBC (under 50,000/mm^3 vs over 50,000/mm^3), steroid allocation, and early response (slow vs rapid).

Patients with verified CNS disease receive weekly intrathecal (IT) methotrexate until 2 consecutive clear cerebrospinal fluid samples have been obtained. Cranial radiotherapy is administered over 15-21 days during weeks 5-8 concurrently with methotrexate IT in the appropriate regimen. Following radiotherapy, these patients receive monthly methotrexate IT for 1 year and then every 3 months until the end of therapy.

Patients with testicular infiltration receive additional radiation fractions daily for 12 days to both testes during weeks 5-8.