CD68+ cell count, early evaluation with PET and plasma TARC levels predict response in Hodgkin lymphoma

Cancer Med. 2016 Mar;5(3):398-406. doi: 10.1002/cam4.585. Epub 2016 Jan 13.

Abstract

Early response evaluation with [(18) F]fluordeoxyglucose (FDG) positron emission tomography after 2 cycles of chemotherapy (interim PET) has been indicated as the strongest predictor for outcome in classical Hodgkin lymphoma (HL). We studied the prognostic role of the number of tumor-infiltrating CD68+ cells and of the plasma levels of TARC (thymus and activation-regulated chemokine) in the context of interim PET in 102 patients with classical HL treated with Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD). After 2 ABVD cycles, interim PET according to Deauville criteria was negative (score 0-3) in 85 patients and positive (score 4-5) in 15 patients (2 patients technically not evaluable). TARC levels were elevated in 89% of patients at diagnosis, and decreased after 2 cycles in 82% of patients. Persistently elevated TARC levels in 18% of patients were significantly associated with a positive PET result (P = 0.007). Strong predictors for progression-free survival (PFS) were a negative interim PET (85% vs. 28%, P < 0.0001) and CD68+ cell counts <5% (89% vs. 67%, P = 0.006), while TARC levels at diagnosis and at interim evaluation had no prognostic role. In multivariate analysis, interim PET, CD68+ cell counts and presence of B-symptoms were independently associated with PFS. We conclude that although TARC levels are a biomarker for early response evaluation, they cannot substitute for interim PET as outcome predictor in HL. The evaluation of CD68 counts and B-symptoms at diagnosis may help to identify low-risk patients regardless positive interim PET.

Keywords: CD68+ tumor-infiltrating macrophages; Hodgkin lymphoma; TARC; interim PET; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / metabolism
  • Cell Count
  • Chemokine CCL17 / blood*
  • Female
  • Fluorodeoxyglucose F18 / metabolism
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / metabolism
  • Hodgkin Disease / pathology
  • Humans
  • Lymphocytes, Tumor-Infiltrating / cytology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CCL17 protein, human
  • CD68 antigen, human
  • Chemokine CCL17
  • Fluorodeoxyglucose F18