Clinicopathological features and prognostic significance of programmed death ligand 1 in pediatric ALK-positive anaplastic large cell lymphoma: results of the ALCL99 treatment in Japan.

Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) blockade is a promising therapy for hematological malignancies. However, the association of PD-L1 expression with the clinicopathological features and prognosis in pediatric ALK-positive anaplastic large cell lymphoma (ALCL) remains unclear. Using PD-L1/ALK immunofluorescence double staining, we evaluated the PD-L1 expression on tumor cells/tumor-infiltrating immune cells (TIICs) and the quantity of TIICs in 54 children with ALK-positive ALCL treated with the ALCL99 protocol. The percentages of PD-L1-positive tumor cells were significantly lower in patients with skin/mediastinum involvement, clinical high-risk group, present minimal disseminated disease (MDD), and a low ALK-antibody titer. The percentages of PD-L1-positive TIICs were significantly higher in patients with absent MDD. The percentages of TIICs were significantly lower in patients with absent MDD and a common morphological pattern. We classified patients according to the PD-L1 expression on tumor cells (Tumor-PD-L1), PD-L1 expression on TIICs (TIIC-PD-L1), and quantity of TIICs (TIIC-quantity). The progression-free survival (PFS) did not differ between Tumor-PD-L1high and Tumor-PD-L1low ALCL; TIIC-PD-L1high and TIIC-PD-L1low ALCL; and TIIC-quantityhigh and TIIC-quantitylow ALCL. According to the combined parameters of Tumor-PD-L1 and TIIC-quantity, Tumor-PD-L1high/TIIC-quantityhigh ALCL had a worse 5-year PFS than other ALCL (50% versus 83%; P = .009). Tumor-PD-L1high/TIIC-quantityhigh ALCL remained a significant prognostic factor in multivariate analysis (P = .044). This is the first study to demonstrate that a high tumoral PD-L1 expression with a high quantity of TIICs was associated with a poor prognosis in pediatric ALK-positive ALCL. The tumor microenvironment of ALK-positive ALCL may be relevant to the clinicopathological features and prognosis.