Relationship between CD45 Expression and Outcomes in B Lymphoblastic Leukemia/Lymphoma

Introduction:

B lymphoblastic leukemia/lymphoma (B-ALL) constitutes the most common type of lymphoblastic leukemia, with about two thirds of the cases being of B-cell lineage. It represents a significant cause of cancer related morbidity and mortality in both pediatric and adult populations. B-ALL immunophenotype has been extensively studied and used for diagnosis. Recent data underscores the importance of the CD45 transmembrane phosphatase in the modulation of signal transduction pathways in leukemic cells. In fact, the gene encoding CD45, PTPRC, has been identified as a tumor suppressor that is deleted in 10% of cases of T-ALL. Based on the impact of CD45 on leukemic cell biology, we hypothesized a relationship between CD45 protein expression and clinical parameters.

Methods:

This is a retrospective, single center analysis of patients diagnosed with B-ALL at Indiana University Simon Comprehensive Cancer Center from December 2003 until December 2018. Patients were followed until July 2020. Variables included patient demographics, and clinical and treatment characteristics. B-ALL diagnosis, molecular profiles, and clinical outcomes were abstracted by chart review. Descriptive statistics were used to summarize baseline characteristics and outcomes. Flow cytometry analysis was performed using 4- and 10-color leukemia screening panel. Median and geometric mean of CD45 antigen intensity was analyzed using FCS Express V6 software. Statistical analysis was performed using SPSS statistical package.

Results:

A total of 148 BALL patients were included in the analysis. 19 (12.8%) were adults (>18 years old) and 13 (8.7%) were Philadelphia chromosome positive. Average Median CD45 expression and CD45 Geometric Mean were 22.9 and 21.9 respectively for the entire cohort. Relevant clinical outcomes collected included complete remission (CR) at days 14 and 29, presence of minimal residual disease (MRD) at days 7 and 29, relapse of disease and death. Mann-Whitney Test was used to establish association between CD45 levels and clinical outcomes. A significant association was found between achieving CR at 29 days and lower levels of CD45 expression (as defined by median and geometric mean, p=0.03 for both). The association was was maintained when excluding Philadelphia positive cases (p=0.05 for both) and excluding patients over 30 years old (p=0.05 for both). There were no significant correlations between CD45 expression and other clinical variables.

Conclusions:

Lower CD45 expression as determined by flow cytometry is associated with higher rates of CR at 29 days. This finding is significant across different age groups and Philadelphia negative cohorts. This finding needs to be explored in further studies. CD45 protein expression levels could be an important biomarker for adjusting induction chemotherapy to achieve complete remission.