Progress in Myelodysplastic Syndromes: Clinicopathologic Correlations and Immune Checkpoints

Clin Lymphoma Myeloma Leuk. 2017 Jul:17S:S16-S25. doi: 10.1016/j.clml.2017.02.022.

Abstract

Background: Myelodysplastic 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 methods: We 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.

Results: Bone 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.

Conclusion: BM morphology and PD-L1 expression by immunohistochemistry can be used to assess treatment response in immune checkpoints therapy.

Keywords: Checkpoint inhibitors; Immunotherapy; PD-1; PD-L1; T cells.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • B7-H1 Antigen / metabolism*
  • Bone Marrow / drug effects
  • Bone Marrow / pathology*
  • CTLA-4 Antigen / metabolism
  • Disease Progression
  • Female
  • Flow Cytometry
  • Hematopoiesis / drug effects
  • Humans
  • Immunophenotyping
  • Male
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / pathology*
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / metabolism*
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor