Prognostic importance of CD56 expression in intermediate risk acute myeloid leukaemia

Recently, we showed that clinical outcomes of Brazilian acute myeloid leukaemia (AML) patients were significantly inferior to those in the USA and Europe. Excluding well-recognized differences between developed and developing countries, heterogeneity in outcome still exists in patients with the same cytogenetic risk (Lima et al, 2015). Therefore, it would be interesting to identify supplementary biological markers that yield non-redundant biological information for further prognostic refinement of AML patients. In this context, aberrant expression of CD56 antigen (also termed NCAM1) in leukaemic blasts has been frequently associated with inferior outcome in patients with AML, particularly those with t (8;21) (Iriyama et al, 2013) and t(15;17) abnormalities (Montesinos et al, 2011). Nevertheless, knowledge regarding its prognostic value in other subtypes of AML remains limited. Here, we evaluated clinical outcomes of non-selected patients with AML (non-acute promyelocytic leukaemia) according to CD56 expression. Our data suggest that aberrant expression of this antigen may predict inferior outcome in patients with intermediate outcome. One hundred and forty-one newly diagnosed AML patients were included between August 2008 and April 2015, with last follow-up in May 2015. Patients were classified according to morphological, immunophenotypic and cytogenetic findings. Treatment protocol was previously described (Lima et al, 2015). The local Research Ethics Board approved the study. To determine CD56 antigen expression, immunophenotypic analysis was accomplished using diagnostic bone-marrow samples and standard flow-cytometry methods. Patients were designated ‘CD56-positive’ when ≥20% of leukaemic cells expressed CD56 antigen (Bene et al, 1995). Fisher’s exact test or Chi-square test, as appropriate, was used to compare categorical variables. Wilcoxon rank-sum test was used to compare continuous variables. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan–Meier method. OS was defined as the time from the initiation of induction therapy to death from any cause; those alive or lost to follow-up were censored at the date last known alive. DFS was defined as the time from complete remission to disease relapse, development of secondary malignancy, or death from any cause, whichever occurred first. Patients who were alive without disease relapse or secondary malignancy were censored at the time last seen alive and disease-free. The log-rank test was used for comparisons of Kaplan–Meier curves. Univariate and multivariate proportional hazards regression analysis was performed for potential prognostic factors for OS and DFS (Table I). Potential prognostic factors examined in multivariate regression analysis were CD56 expression, cytogenetic risk stratification, age at diagnosis and leucocyte counts. Proportional hazards assumption for each variable of interest was tested. Linearity assumption for all continuous variables was examined using restricted cubic spline estimates of the relationship between the continuous variable and log relative hazard/risk. All P-values were two sided with a significance level of 0 05. All calculations were performed using Stata Statistic/Data Analysis version 12 (Stata Corporation, College Station, TX, USA) and R 2.10. 1 (The CRAN project, www.r-project.org) software.