ALL-373 Immunophenotype of MRD Cells as an Additional Prognostic Marker

Abstract

Measurable residual disease (MRD) is an independent prognostic factor in acute lymphoblastic leukemia (ALL). However, the impact of the immunophenotype of MRD cells on survival has not been studied. To determine the significance of the immunophenotype of MRD cells detected at the end of induction in patients with ALL. This study included data from 2016 to 2022 for 267 patients enrolled in the Russian multicenter study RALL-2016 (NCT03462095). MRD was assessed on day 70 in patients with complete remission. MRD was assessed in 94 B-ALL and 77 T-ALL patients. Analysis of MRD was performed by 6-11-color flow cytometry. CD19, CD34, CD10, CD20, CD38, CD45, and CD58 were analyzed to detect MRD in all B-ALL patients. CD7, CD3surface, CD3cytoplasmic, CD4, CD8, CD5, CD99, and CD45 were analyzed to detect MRD in T-ALL patients. The expression of these antigens was assessed relative to normal bone marrow cells and transformed into a numeric score. A dendrogram was constructed using the "ward.D" method in R 3.4.4. Relapse-free survival (RFS) was estimated by the Kaplan-Meier method, and comparisons were assessed using the log-rank test. MRD was revealed in 37 (39%) B-ALL and 18 (23.4%) T-ALL patients. RFS was lower in MRD-positive patients (54% vs. 90% [p<0.0001] in B-ALL and 59% vs. 83% [p<0.0025] in T-ALL) than in MRD-negative patients. In B-ALL, 3 clusters of MRD cells were detected. Cluster I (n=16) included cases of CD10+MRD, whereas clusters II (n=13) and III (n=8) included CD10-MRD. Expression of CD38 and CD58 was higher in cluster II than in cluster III. RFS rates were 62%, 33%, and 71% (p=0.043) in clusters I, II, and III, respectively. In T-ALL, 3 clusters were also found. Cluster I included 3 CD7- cases, cluster II included 9 CD7+CD5+CD3dim/+ cases, and cluster III included 6 CD7highCD5-/dimCD3- cases. RFS rates were 33%, 49%, and 100% (p=0.015) for clusters I, II, and III, respectively. MRD at the end of induction impaired RFS in patients in the RALL-2016 study. The immunophenotype of MRD cells is associated with RFS and could be an additional prognostic factor.