Outcome of risk-adapted therapy for pediatric acute lymphoblastic leukemia in Egypt.

Abstract

10044 Background: With modern risk directed therapy, >80% of children with acute lymphoblastic leukemia (ALL) in western countries are cured. The 5-year event free survival (EFS) and relapse free survival (RFS) of pediatric ALL patients in Egypt were 65% and 75% respectively in a previous study using an intensive treatment protocol for all patients. Aim: To improve cure rates of Egyptian children with ALL using risk adapted therapy. Methods: From July 2007 to December 2010, 706 patients aged 1-18 years with newly diagnosed ALL were treated at Children Cancer Hospital Egypt with a risk directed ALL protocol adopted from St Jude Total Study XV. Results: B-precursor phenotype was encountered in 75.8% and T-cell in 24.2%. Based on initial presentation and response to therapy measured by minimal residual disease (MRD), 42.6%, 45.8% and 11.6% of the patients were classified as low, intermediate and high risk respectively. The 5-year RFS and EFS were 88.2 ± 1.5% and 76.5 ± 1.7% respectively. Adverse events included 4.4% induction deaths, 2.5% failure to achieve induction remission (1.4% remained refractory), 6.8% deaths in remission, 9.2% relapses (3.1% hematological, 1.8% combined hematological and CNS, 4% isolated CNS, 0.3% isolated testicular), 0.9% abandonment of therapy and one patient had secondary myeloid leukemia. The median follow up for patients alive in CR was 43months (range 24–65). The 5-year RFS of the low, intermediate and high risk groups were 92.2 ± 2.4%, 85.3 ± 2.2% and 82.7 ± 4.8% respectively (p=0.001), while the 5-year EFS were 87.6 ± 2.5%, 78.2 ± 2.5% and 57.9 ± 5.7% respectively (p<0.001). Prognostic factors that had statistically significant unfavorable impact on both EFS and RFS by univariate analysis were age ≥10 years, TLC ≥100x109/L, T-cell phenotype, risk groups, MRD d42 ≥1% and MRD W7 ≥0.1%, while MRD d15 ≥1% had statistically significant unfavorable outcome on EFS only. By multivariate analysis, TLC and MRD W7 had prognostic significance on EFS and RFS, MRD d42 on EFS, while MRD d15 had marginal significance on EFS (p=0.055). Conclusions: Risk adapted therapy was effective in improving ALL survival among patients at our institution compared with previous trials, although the outcome remains lower than that in high income countries.