ORLANDO, FL—Immunophenotypic expression profiles can discriminate cohorts of patients with childhood acute myeloid leukemia (AML) that have a high probability of relapse, a study using data from a Children’s Oncology Group study presented at the 57th American Society of Hematology (ASH) Annual Meeting has shown.1
Such profiles can also detect when residual disease, as measured by multidimensional flow cytometry at end of induction 1, “is predictive of patient outcome,” said Lisa Eidenschink Brodersen, PhD, of Hematologics Inc. in Seattle, WA.
The study “investigated the relationship between presenting immunophenotype and response to therapy in a large, controlled study” of 769 newly diagnosed pediatric patients with AML, a subset of the 1022 patients enrolled on the group’s protocol AAML0531.
The 769 patients had submitted a bone marrow specimen for measurable residual disease with multidimensional flow cytometry at diagnosis and consented for specimen testing. Patients with acute promyelocytic leukemia or Down syndrome were excluded.
“All diagnostic and post-treatment specimens underwent central multidimensional flow cytometry analysis at Hematologics,” Dr Brodersen said.
The study average 5-year event-free survival rate was 49%, Dr Brodersen said, with a study average presence of minimal residual disease at initial induction of 35%.
Hierarchical clustering analysis of the immunophenotypic expression profiles defined 11 groups of patients with similar quantitative diagnostic immunophenotypes, defined as groups A-K.
Five immunophenotypic groups of patients were associated with comparable end of induction 1 measurable residual disease rates (15% to 36%) and event-free survival (50% to 69%) to the study average. These 5 groups, designated A-E, comprised immunophenotypes “close to the normal counterpart of myeloid progenitor cells or normal monocytes,” she said.
Two immunophenotypic patient groups (F and G) were associated with significantly higher rates of measurable residual disease (and lower event-free survival (group F, 28%; P < .001; group G, 19%; P < .001) than average for the study.
“The defining different-from-normal immunophenotypic features of group F were expression of CD34 with a lack of HLA-DR. The defining immunophenotypic features of group G were high intensity CD56 expression, a lack of HLA-DR, dim-to-negative CD38 expression and dim-to-negative CD45 expression. The majority of patients in both groups were stratified as low or standard risk (86% and 100%),” Dr. Brodersen said.
Three immunophenotypic groups (H, I, and J) had low rates of measurable residual disease (20%-24%) but poor event-free survival (27%-39%). In group H, the defining different-from-normal immunophenotypic features were CD56 expression and CD13 with a lack of CD34; for group I, CD34 positive expression with a lack of CD117; and for group J, bright CD11b expression with a lack of CD34 and CD117. In these groups, 94%, 100%, and 75%, respectively, of patients were stratified as standard risk.
Group K had a high rate of measurable residual disease (50%) and comparable event-free-survival (52%) to the study average, with defining different-from-normal features of CD56 expression with a lack of CD34 and CD13.
“Immunophenotypic expression profiles provide a powerful tool to discriminate patient cohorts that have a high probability of relapse,” Dr. Brodersen concluded, noting that the study identified 4 groups of patients—91% otherwise stratified as good or standard risk—who had poor outcomes. The researchers are now seeking to validate these findings.
1. Loken MR, Voigt AP, Gerbing RB, et al. Heirarchical clustering of immunophenotypic cell surface antigen expression identifies clinically meaningful cohorts in childhood AML: a report from the Children’s Oncology Group Protocol AAML0531. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting; December 7, 2015, Orlando, FL.