Adaptive immune and platelet activation during the maintenance phase of therapy in adults with B cell acute lymphoblastic leukemia.

BACKGROUND Maintenance therapy is an integral component of treatment for B cell acute lymphoblastic leukemia (B-ALL) and has demonstrated clinical efficacy. However, features of immune activation and an increased thrombotic risk may persist beyond the induction phase of treatment. The mechanisms underlying immune activation during the maintenance phase of B-ALL remain unclear. Therefore, this study aimed to evaluate immune activation and thrombotic risk in adult patients with B-ALL undergoing maintenance therapy. METHOD This prospective study was conducted at Windhoek Central Hospital and Katutura State Hospital in Namibia. Adult patients with B-ALL receiving maintenance therapy (n = 16) and eighteen controls (n = 18) were enrolled. Plasma concentrations of D-dimer, thrombin, and platelet factor 4 (PF-4) were quantified using enzyme-linked immunosorbent assay and the surface expression of immune checkpoint and activation markers on CD4+ T cells, B lymphocytes, and platelets were measured using flow cytometry. RESULTS Patients with B-ALL demonstrated elevated thrombin (p = .01) and PF4 (p = .02) concentrations compared with healthy controls. In addition, the expression of the activation marker CD69 (p < .001), and immune checkpoints PD-L1 (p < .001) and CTLA-4 (p < .001) were increased on the surface of CD4+ T cells. While PD-1 expression remained comparable between the groups (p = .90). On B lymphocytes, CD69 expression levels were similar between groups (p = .11). Whereas the levels of PD-L1 (p < .001) and CTLA-4 (p = .02) were elevated. Notably, PD-1 expression was reduced in patients with B-ALL (p = .02). The expression of CD62P was increased in patients with B-ALL when compared with controls (p < .001). CONCLUSION Adult patients with B-ALL undergoing maintenance therapy exhibits increased lymphocyte and platelet activation, which may be associated with an elevated thrombotic risk despite normal D-dimer levels.