Abstract

Early response to therapy is one of the most important prognostic factors in childhood ALL. In the early 1980s, assessment of early treatment response to therapy relied mainly on morphological examination of peripheral blood or bone marrow after single-agent or multi-agent remission induction therapy. More recently, measurement of minimal residual disease (MRD) by flow cytometric detection of aberrant immunophenotype or by polymerase chain reaction of clonal T-cell receptor or immunoglobulin gene rearrangement emerged as a more reliable prognostic indicator. We evaluated the prognostic significance of early treatment response in our recent clinical trial. Among the children with ALL who entered protocol of ALL-XH-99 from January 1998 to May 2003, 193 patients with newly diagnosed ALL comprise the basis for this report. We examined blast cell count in the bone marrow on day 19 of remission induction and at the end of 35 days of remission induction. Minimal residual disease was measured with the use of flow cytometry. Probability of event-free survival was estimated by Kaplan-Meier analysis and the distributions of pEFS were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Univariate analysis indicated the probability of 4-year event-free survival (pEFS) was significantly worse for patients with ≥ 5% lymphoblasts in the bone marrow on day 19 as compared to those with less than 5% lymphoblasts on that date (42.59%±14.28% vs 74.24%±6.67%, P=0.0006). The probability of 4-year event-free survival (pEFS) was significantly worse for patients with any amount of lymphoblasts in the bone marrow on the remission date as compared to that of other patients with no morphologically identifiable blasts (63.47%±9.23% vs 76.41%±6.09%, P=0.0130). Patients who achieved a minimal residual level < 0.01%, fared significantly better than those with a higher level. (23.81%±20.26% vs 94.44%±5.4%, P=0.001). Early treatment response as assessed by morphologic examination or minimal residual leukemia determination by flow cytometry has important prognostic significance, and can be performed in a resource-poor patient population.

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