Circulating myeloid-derived suppressor cells correlate with clinical outcome in Hodgkin Lymphoma patients treated up-front with a risk-adapted strategy

Br J Haematol. 2015 Mar;168(5):689-700. doi: 10.1111/bjh.13198. Epub 2014 Nov 7.

Abstract

In the attempt to find a peripheral blood biological marker that could mirror the dysregulated microenvironment of Hodgkin Lymphoma (HL), we analysed the amount of myeloid-derived suppressor cells (MDSC), including the three main sub-types (monocytic, granulocytic and CD34 + fraction). The absolute MDSC count was investigated in 60 consecutive newly diagnosed HL patients and correlated with clinical variables at diagnosis and outcome. Patients received standard-of-care chemotherapy with the exception of interim fluorodeoxyglucose positron emission tomography (PET-2)-positive patients, who were switched early to a salvage regimen. All MDSC subsets were increased in HL patients compared to normal subjects (P < 0·0001) and were higher in non-responders. However, a strong prognostic significance was limited to immature (CD34(+) ) MDSC. A cut-off level of 0·0045 × 10(9) /l for CD34(+) MDSC resulted in 89% (95% confidence interval [CI] 52-99%) sensitivity and 92% (95% CI 81-98%) specificity. The positive predictive value to predict progression-free survival was 0·90 for PET-2 and 0·98 for CD34(+) MDSC count; the negative predictive value was 0·57 for PET-2 and 0·73 for CD34(+) MDSC. PFS was significantly shorter in patients with more than 0·0045 × 10(9) CD34(+) MDSC cells/l at diagnosis and/or PET-2 positivity (P < 0·0001). In conclusion, all circulating MDSC subsets are increased in HL; CD34(+) MDSC predict short PFS, similarly to PET-2 but with the advantage of being available at diagnosis.

Keywords: hodgkin lymphoma; myeloid-derived suppressor cells; positron emission tomography-2.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD34*
  • Disease-Free Survival
  • Female
  • Hodgkin Disease / blood*
  • Hodgkin Disease / diagnostic imaging
  • Hodgkin Disease / mortality*
  • Hodgkin Disease / therapy
  • Humans
  • Leukocyte Count
  • Male
  • Middle Aged
  • Myeloid Cells*
  • Positron-Emission Tomography
  • Prospective Studies
  • Radiography
  • Survival Rate

Substances

  • Antigens, CD34