Expression of CD56 defines a distinct subgroup in childhood T‐ALL with inferior outcome. Results of the ALL‐BFM 2000 trial

Summary This study reports the prognostic impact of the expression of the natural killer cell marker CD 56 in a large series of risk‐adapted paediatric patients with T cell acute lymphoblastic leukaemia (T‐ALL; n = 493) treated within the ALL ‐Berlin‐Frankfurt‐Münster ( BFM ) 2000 protocol. The immunophenotype was analysed centrally at diagnosis using flow cytometry and correlated with clinical parameters and outcome. CD 56 expression was detected in 7·1% and early T‐cell precursor ( ETP ) phenotype in 6·7% of all T‐ ALL patients. The percentage of ETP in the CD56+ T‐ALL cohort was 4‐fold higher than in the whole cohort. CD56+ T‐ ALL frequently expressed the progenitor marker CD 34 and myeloid antigens CD 13 and CD 33. The 5‐year event‐free survival ( EFS ) rates for the European Group for the Immunological classification of Leukaemias/World Health Organization subgroups and the ETP phenotype were not statistically different. By contrast, patients with CD 56 expression had a significantly reduced EFS (60 ± 8%) and overall survival (60 ± 8%) at 5 years, with a hazard ratio of 2·46 ( P = 0·002) and 2·99 ( P < 0·001), respectively. Moreover, CD 56 expression in combination with the minimal residual disease ( MRD )‐based high risk assignment defined a population with a ‘very‐high’ risk probability of relapse in the ALL ‐ BFM 2000 trial. The CD 56 marker has the potential to augment MRD ‐based risk stratification and may serve as a molecular target for antibody‐based treatment strategies in childhood T‐ ALL .