High frequency of immature cells at diagnosis predicts high minimal residual disease level in childhood acute lymphoblastic leukemia

Abstract 

Prognosis for children with acute lymphoblastic leukemia (ALL) has considerably improved, yet relapse still occurs in a significant proportion of patients. Conceivably, the most immature leukemia cells may be more resistant to therapy and initiate relapse. We studied 42 patients with childhood ALL treated according to the ALL-BFM 2000 protocol. At diagnosis, we determined the characteristic immunophenotype of the leukemic cells by flow cytometry and also investigated the expression of CD34 and CD38 to define a population of immunophenotypically immature cells (CD34⁺/CD38⁻). We then studied levels of minimal residual disease (MRD) after induction therapy (day 33) and after consolidation therapy (week 12). We found a significant, increasing correlation between the prevalence of CD34⁺/CD38⁻ cells at diagnosis and MRD levels at day 33 and week 12. Our results suggest that the initial frequency of CD34⁺/CD38⁻ cells may serve as a prognostic marker in pediatric ALL.

Keywords: Acute lymphoblastic leukemia, Leukemic stem cell, Immature leukemic cell fraction, Minimal residual disease, Prognostic factor