Autologous stem-cell transplantation restores the functional properties of CD14+CD16+ monocytes in patients with myeloma and lymphoma.
The CD14+CD16+ monocytes appear to be important to immune defense against infection, as these cells are very potent with respect to tumor necrosis factor (TNF) production, phagocytosis, and antigen presentation. Myeloablative high-dose chemotherapy (HDT) and subsequent autologous stem-cell transplantation (ASCT) are being used increasingly for therapy of hematological malignancies, but the pronounced immunosuppression renders the patients prone to infection. To determine the functional properties of CD14+CD16+ monocytes under these conditions, 15 patients with lymphoma or myeloma were examined. Before HDT, the ratio of CD14+CD16+ cells to the population of the classical CD14++ monocytes was 0.28 +/- 0.12; this ratio changed during the course of HDT and ASCT in favor of the CD14+CD16+ monocytes to a maximum of 12.4 +/- 7.8 (P<0.001) on day 3.5 +/- 1.6 after transplanation (Tx) and returned to 0.11 +/- 0.07 (P<0.001) after engraftment on day 11.3 +/- 2.2. Although the absolute number of classical CD14++ monocytes declined to less than 1/microl at the nadir, the number of CD14+CD16+monocytes fell from 29.7 +/- 9.8/microl to 4.5 +/- 3.0/microl at the nadir and increased to 13.8 +/- 9.8/microl at the day of discharge from the hospital. Flow cytometric analysis of phagocytosis of fluorescein isothiocyanate (FITC)-labeled Escherichia coli showed that 30 +/- 10% CD14+CD16+ monocytes of patients were FITC-positive before Tx, and at engrafment, the percentage of FITC-positive cells had doubled to 60 +/- 6% (healthy controls, 41+/-7%). When determining generation of reactive oxygen species after E. coli ingestion, the CD14+CD16+ monocytes showed a decreased response before Tx (32+/-12% positve cells), which increased to 53 +/- 24% after ASCT. The median fluorescence intensity of human leukocyte antigen (HLA)-DR expression on the CD14+CD16+ monocytes increased from 11 +/- 6 before Tx to 17 +/- 11 after Tx, and the production of TNF after lipopolysaccharide showed no remarkable difference (46+/-13 vs. 49+/-14 channels). At the same time, expression of TNF and of HLA-DR showed a dramatic decrease in the CD14++ monocytes. Taken together after stem-cell Tx, the function of the CD14++ monocytes is impaired, and the functional properties of CD14+CD16+ monocytes recover, indicating that these cells may be important for defense against infections post-ASCT.
Department of Hematology and Oncology, Medical Clinic Campus Innenstadt, University of Munich, Ziemmssenstrasse 1, 80336 Munich, Germany. dayyani@web.de
Farshid
F
Dayyani
Anke
A
Joeinig
Löms
L
Ziegler-Heitbrock
Ralf
R
Schmidmaier
Christian
C
Straka
Bertold
B
Emmerich
Gerold
G
Meinhardt
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D006684:HLA-DR Antigens; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018950:Lipopolysaccharide Receptors; D008223:Lymphoma / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000502:physiology*; D009101:Multiple Myeloma / Q000628:therapy*; D010587:Phagocytosis; D017452:Receptors, IgG; D016897:Respiratory Burst; D014182:Transplantation, Autologous; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha