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

Abstract

This study reports the prognostic impact of the expression of the natural killer cell marker CD56 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. CD56 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 CD34 and myeloid antigens CD13 and CD33. 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 CD56 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, CD56 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 CD56 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.

Identification of prognostic factors in childhood T‐cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05‐001 and 11‐001

“…18,20,21 However, in more recent reports, despite an association with slow early response, ETP status has lacked prognostic significance. [22][23][24] While multiple recurrent genomic aberrations have been identified in T-ALL, 25,26 few have been reproducibly associated with prognosis and none are prospectively used in risk stratification. Activating mutations of the Notch pathway are found in over 50% of T-ALL cases, 25,27,28 and have been associated with favorable outcomes in pediatric and adult T-ALL studies, albeit inconsistently.…”

“…In initial reports, ETP status was associated with high rates of induction failure, early relapse, and poor overall survival 18,20,21 . However, in more recent reports, despite an association with slow early response, ETP status has lacked prognostic significance 22–24 …”

A narrative review of central nervous system involvement in acute leukemias

“…The genetic mutations found in the CD56+ group, that carry the mutations NOTCH1, PTEN and FBXW7, appear to have a similar distribution as for CD56− group such that they cannot link that immunophenotype to any genetic mutation. Also, the clinical progression of ALL showed significant differences only when patients are stratified according to CD56 expression profile (178).…”

Relevance of flow cytometric categorization and end-of-induction measurable residual disease assessment in pediatric and adult T-lymphoblastic leukemia patients

“…Regarding cross-lineage antigen expression among T-ALL blasts, expression of the CD56 antigen of natural killer (NK) cells is frequently associated with ETP-ALL blasts and confers a poor prognosis [ 24 - 27 ]. Consistent with the literature, we also observed a higher frequency of CD56 expression in our ETP-ALL and near-ETP-ALL patients ( P =0.009).…”