Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children's Cancer Study Group Study L99-15

Abstract

Treatment response has become one of the most important prognostic factors in childhood acute lymphoblastic leukemia. We evaluated the significance of the complete clearance of peripheral leukemic blasts on survival in children with acute lymphoblastic leukemia. Seven hundred and fifty-four children diagnosed with acute lymphoblastic leukemia, consecutively enrolled from 1999 to 2003 in the TCCSG L99-15 study, were eligible for analysis. Patients were stratified into three risk groups based on presenting features, such as age and the leukocyte count before starting the treatment, followed by reclassification into three categories 7 days after prednisolone monotherapy based on the peripheral blast count; 0/microL (Day8NoBlasts), 1-999/microL and >or= 1,000/microL. After 7 days of prednisolone monotherapy, 249 patients (33%) were classified as Day8NoBlasts, 392 patients (52%) had blast counts of 1-999/microL, and 113 patients (15%) had blast counts >or= 1,000/microL. The event-free survival for all patients was 79.6+/-1.6 (SE)% at 4 years, whereas that for patients with Day8NoBlasts was 90.4+/-2.0% (n=249) and the event-free survival for the other patients was 74.2+/-2.2% (n=504) (log rank p<0.001). The event-free survival for Day8NoBlasts patients with B-lineage acute lymphoblastic leukemia and T-cell acute lymphoblastic leukemia was 89.8+/-2.1% (n=226) and 95.7+/-4.3% (n=23), respectively. In a multivariate analysis, age at diagnosis, the initial white blood cell count, immunophenotype, and gender did not remain as independent risk factors for treatment failure, whereas Day8NoBlasts and marked hyperdiploidy (more than 50 chromosomes) became statistically significant. Children with Day8NoBlasts constituted one third of all the cases with childhood acute lymphoblastic leukemia with an excellent outcome, and should be candidates for curative management with less intensive treatment.