Progress in Myelodysplastic Syndromes: Clinicopathologic Correlations and Immune Checkpoints


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Abstract

BackgroundMyelodysplastic syndromes (MDS) are a group of clonal neoplasms characterized by ineffective hematopoiesis. Hypomethylating agent (HMA) therapy is one of the mainstays of MDS therapy. Failure of HMA therapy is related to poor outcome; hence, new therapeutic approaches are warranted in these patients. In MDS, the immune system has a pivotal role in modulation of hematopoiesis and clonal expansion. In neoplastic conditions, immune checkpoint (PD-1 and CTLA4 molecules) hide tumor cells from immune surveillance. Identification of the pattern of expression of these molecules in MDS provides an interesting alternative within clinical trials.Materials and MethodsWe describe the clinicopathologic correlations by morphology, immunohistochemistry (PD-L1) and flow cytometry immunophenotypic analysis in an MDS patient treated with immune checkpoint PD-1 inhibitor.ResultsBone marrow (BM) morphology, differential counts and aberrant flow markers were assessed before and after anti PD-1 inhibitor therapy. At baseline, BM showed severe trilineage dysplasia with decreased granulopoiesis; after therapy, BM showed normal trilineage hematopoiesis. A decrease in PD-L1 expression, by manual and automatic analysis, was also noted from 15% to 5% after 26 months of treatment. The findings correlated with the recovery of peripheral blood counts and transfusion independency.ConclusionBM morphology and PD-L1 expression by immunohistochemistry can be used to assess treatment response in immune checkpoints therapy.Micro-AbstractIn MDS, hypomethylating agents (HMA) failure is related to poor outcome. HMA up-regulates immune checkpoints in blasts. We describe the clinicopathologic correlations in an MDS patient treated with PD-1 inhibitor and assessed PD-L1 expression in bone marrow (BM). BM morphology and PD-L1 expression by immunohistochemistry can be used to assess treatment response.

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