Circulating endothelial cell kinetics and their potential predictive value during mobilization procedure

J Clin Apher. 2013 Oct;28(5):341-8. doi: 10.1002/jca.21277. Epub 2013 May 16.

Abstract

Objective: Circulating endothelial cells (CECs) in patients with hematological malignancies are assessed as a noninvasive marker of angiogenesis. The aim of this study was to evaluate the numbers of CECs and their subsets during mobilization of hematopoietic stem cells.

Patients and methods: Thirty-eight patients were enrolled to the study (19 females and 19 males) at median age of 56.5 years. The group consisted of patients with multiple myeloma (26), lymphoma (10), and acute myeloid leukemia (2). Blood samples were collected before chemotherapy (0), 1 day after chemotherapy (Cht+1), on the day G-CSF commenced (G0), after 1 day of G-CSF (G+1), and on the day of the first apheresis. CECs were evaluated by four-color flow cytometry. Circulating progenitor cells were defined as CD45-/CD34+/CD31+/CD133+. Apoptotic CECs (ApoCECs) were defined as CD146+/AnnexinV+.

Results: Median (Me) CECs number was 10.5/µl and it decreased after chemotherapy (Me = 8.3/µl, P < 0.001 when compared with baseline). Based on the number of aphereses needed to obtain 2 × 10(6)/kg CD34+ cells, patients were divided into "highly efficient" (one apheresis) and "poorly efficient" mobilizers (two or more aphereses). Median ApoCEC at Day G+1 was lower in highly efficient than in poorly efficient mobilizers (Me = 3.1/µl vs. Me = 5.1/µl, P = 0.02). ApoCEC at Day G+1 correlated with the number of aphereses (r = 0.48, P = 0.03). In multivariate analysis, ApoCEC at Day G+1 was an independent factor for successful mobilization during one apheresis.

Conclusions: CECs and their subsets change significantly during mobilization of HSCs. ApoCECs measured at the time of G-CSF commencement can predict the efficacy of HSC collection.

Keywords: circulating endothelial cells; efficacy; hematopoietic stem cells mobilization.

Publication types

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

MeSH terms

  • AC133 Antigen
  • Adult
  • Aged
  • Annexin A5 / metabolism
  • Antigens, CD / metabolism
  • Antigens, CD34 / metabolism
  • Apoptosis
  • Blood Component Removal
  • Case-Control Studies
  • Cell Separation
  • Endothelial Cells / cytology*
  • Female
  • Flow Cytometry
  • Glycoproteins / metabolism
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cells / cytology*
  • Humans
  • Leukemia, Myeloid, Acute / therapy
  • Leukocyte Common Antigens / metabolism
  • Lymphoma / therapy
  • Male
  • Middle Aged
  • Multiple Myeloma / therapy
  • Neovascularization, Pathologic
  • Peptides / metabolism
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Time Factors
  • Young Adult

Substances

  • AC133 Antigen
  • Annexin A5
  • Antigens, CD
  • Antigens, CD34
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Granulocyte Colony-Stimulating Factor
  • Leukocyte Common Antigens
  • PTPRC protein, human