Study on the Prognostic Value of Aberrant Antigen in Patients With Acute B Lymphocytic Leukemia

Abstract

Chimeric antigen receptors redirected T cell (CAR-T cell) therapy is an effective means of treating relapsed/ refractory acute B-lymphocytic leukemia, and new targets are needed to solve the recurrence after CART cell treatment. A retrospective analysis of 194 patients with acute B-lymphocytic leukemia showed a poor prognosis for CD123 expression. To improve efficacy, CAR19 can be considered to bind to aberrant antigens such as CD123 to form a bispecific or multispecific antigen in CART cell construction. Background: Approximately 30% to 60% of patients with acute B-lymphocytic leukemia (B-ALL) show as refractory or relapsed, which is one of the major causes of death in patients with BALL , but the methods of the treatment for relapsed/refractory BALL (R/R BALL) are limited. The chimeric antigen receptors redirected T cells (CAR-T cells) have showed a strong anti-leukemia role for BALL. About 90% of patients with R/R BALL treated with CD19-CART cells achieved complete remission. However, 60% to 70% of patients relapsed after CART cells treatment, which may be related to target antigen reduction or escape. New products are urgently needed to prevent and treat antigenic escapes causing recurrence. Patients and Methods: In this article, we retrospectively analyzed the immunophenotype of patients with BALL initially diagnosed in our center from January 2010 to December 2015 to determine whether aberrant antigen expression was associated with the prognosis of patients in order to find new targets for immunotherapy. Results: The results show that disease-free and overall survival in patients without aberrant antigen expression were better than patients with aberrant antigen expression. The most common abnormal antigens were CD123, CD13, and CD56. Correlation analysis showed a negative correlation between aberrant CD123 expression and both disease-free and overall survival. Conclusion: Therefore, in the construction of CART cells in patients with R/R BALL , conventional CD19 can be combined with aberrant antigens such as CD123 to form CARs with bi-specific antigens or multi-specific antigens may achieve the purpose of improving efficacy. However, more clinical trials are needed.

Expression of aberrant markers in acute leukemia at South Egypt Cancer Institute: A retrospective study

“…There was a male predominance in our AL patients, which is in accordance with most studies that noted that the males are more affected (27,(31)(32)(33)(34). In our study there was a pediatric predominance in AL, this may be due to that ALL was more common than AML.…”

CD123 as a Therapeutic Target in the Treatment of Hematological Malignancies

“…More recently, Angelova et al have performed a large screening of CD123 expression on a large set of ALLs, showing that CD123 expression was more prevalent in Philadelphia chromosome-positive patients than in Philadelphia chromosome-negative patients [87]. Importantly, Liu et al reported the existence of a negative correlation between CD123 expression on B-ALL blasts and both disease-free and overall survival [88].…”

High Expression of Interleukin-3 Receptor Alpha Chain (CD123) Predicts Favorable Outcome in Pediatric B-Cell Acute Lymphoblastic Leukemia Lacking Prognosis-Defining Genomic Aberrations

“…By univariate and multivariate analysis, a high percentage of CD123 expression on blasts was identified as an independent favorable prognostic factor in pediatric B-ALL. A retrospective analysis of 194 patients with B-ALL showed abnormal CD123 expression indicated a poorer OS and EFS ( 27 ). This discrepancy might be due to approximately 75% of patients in their center were adult B-ALL patients.…”