The Prognostic Value of the CD8⁺PD-1⁺/CD4⁺PD-1⁺ (PERLS) Ratio for Leukemic Transformation in MDS

Background/Objectives: Myelodysplastic syndromes (MDS) are associated with a significant risk of progression to acute myeloid leukemia (AML), affecting approximately 30% of patients. In high-risk MDS, leukemic transformation may occur within a short time frame, highlighting the need for early and reliable biomarkers of disease progression. Increasing evidence suggests that immune dysregulation and cytotoxic T-cell dysfunction contribute to disease evolution. This study aimed to evaluate PD-1 and CD57 expressions on CD8⁺ T cells and to investigate the CD8⁺PD-1⁺/CD4⁺PD-1⁺ ratio (PERLS) as a potential immunological marker predictive of leukemic transformation. Methods: Thirty-one patients with MDS were prospectively followed over a 12-month period. At baseline, patients underwent routine clinical and laboratory evaluation, including multiparameter flow cytometric assessment of bone marrow blasts. An extended immunophenotypic analysis of bone marrow samples was performed at study entry to assess PD-1 and CD57 expression on CD8⁺ T cells. Cytogenetic and molecular analyses were conducted when clinical findings suggested disease progression. Patients who developed signs of progression were re-evaluated approximately one month later, during the progression phase, to assess dynamic immunological changes. Results: Of the thirty-one patients included, eighteen progressed to AML, whereas thirteen remained clinically stable. Patients who progressed demonstrated a significant increase in PD-1 and CD57 expression on CD8⁺ T cells compared with stable patients. Moreover, a markedly higher CD8⁺PD-1⁺/CD4⁺PD-1⁺ (PERLS) ratio was observed in patients who subsequently developed AML, particularly during the progression phase. Conclusions: Dynamic immunophenotypic monitoring reveals that increased PD-1 on CD8⁺ T cells and an elevated PERLS ratio are associated with imminent leukemic transformation in MDS. These findings support the incorporation of immune-based biomarkers, particularly the CD8⁺PD-1⁺/CD4⁺PD-1⁺ ratio, into routine risk assessment to enable earlier identification of disease progression and timely therapeutic intervention.