Favorable outcome in 20-year follow-up of children with very-low-risk ALL and minimal standard therapy, with special reference to TEL-AML1 fusion.

摘要

BACKGROUND: As the treatment results of childhood ALL have improved, avoidance of late effects has become increasingly important. Identification of favorable prognostic factors helps to achieve this goal. PROCEDURE: We studied the prognostic value of TEL-AML1 fusion and a risk factor composed of age, white blood cell count (WBC), lymphomatous features, and hemoglobin level (Hb). We also compared outcome between two cohorts; cohort 1 (n=100) diagnosed 1975-1981, and cohort 2 (n=102) 1989-1991. Both cohorts were retrospectively divided in two groups: very-low-risk (WBC <10 x 10(9)/L, age 2 to <10 years, no lymphomatous features, Hb <90 g/L), and non-low-risk (=the remainder). We performed fluorescent in situ hybridization (FISH) of TEL-AML1 fusion of the marrow samples obtained at diagnosis. RESULTS: The median follow-up is 20 years in cohort 1, and 8 years in cohort 2. In both cohorts, the very-low-risk category comprised one-fourth of the children. TEL-AML1 fusion was more frequent in the very-low-risk(35%) than in the non-low-risk group (17%) (P=0.03). The 8-year event-free survival (EFS) of children with the fusion was better than of those without, 74 vs. 54% (P=0.040). The 8-year EFS in the very-low-risk group was 76% in cohort 1, and 79% in cohort 2 (n.s.). In the non-low-risk groups, EFS was 39 vs. 64% (P=0.02), respectively. CONCLUSIONS: Our data support the reported association of TEL-AML1 fusion with a favorable outcome although the risk group had a greater impact. These very-long-term follow-up data also indicate that children with very-low-risk ALL (slow disease) had a favorable outcome already in the late 1970s, and may be over treated with the contemporary ALL protocols.