The long-term impact of in vitro drug sensitivity on risk stratification and treatment outcome in acute lymphoblastic leukemia of childhood (CoALL 06-97)

Background In a study of childhood acute lymphoblastic leukemia (CoALL 06-97 study), the in vitro sensitivityof the patients' cells to prednisolone, vincristine and asparaginase was introduced as anew additional risk parameter for treatment stratification. In parallel in vivo treatment responsewas assessed by determining the presence and extent of minimal residual disease in a subset ofpatients (n=224). Here we report the long-term impact of in vitro sensitivity-based risk stratificationaccording to survival and compare the results of in vitro sensitivity with in vivo response. Design and Methods Patients with a sensitive in vitro profile were treated with a reduced intensity protocol (n=167)whereas patients defined as low risk according to conventional parameters but with a resistantin vitro profile were given intensified therapy (n=47). Results At a median follow-up of 6.8 years event-free survival was 0.80±0.03 for patients with a sensitiveprofile, 0.73±0.03 for those with an intermediate profile and 0.67±0.08 for those with aresistant profile (P=0.015). Overall, the treatment results of the cases stratified according to invitro sensitivity were similar to those of the historical control group stratified based on conventionalrisk factors. Minimal residual disease at the end of induction was a strong predictor ofoutcome in B-precursor and T-cell acute lymphoblastic leukemia. There was no correlationbetween in vitro and in vivo treatment response in B-precursor leukemia (Spearman's r=0.13;P=0.15) in contrast to T-cell acute lymphoblastic leukemia (Spearman's r=0.63; P<0.001) Conclusions A moderate reduction in treatment intensity for patients with a sensitive in vitro profile waspossible without jeopardizing treatment outcome. However, in vitro drug testing was affectedby a decrease in risk predictive power over time and was not correlated with in vivo assessmentof minimal residual disease in B-precursor acute lymphoblastic leukemia. It was, therefore,abandoned in favor of the assessment of in vivo response in subsequent CoALL trials.

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