Department of Haematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland
We investigated the serum concentrations of selected angiogenic cytokines including: vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGF‐β1) and basic fibroblast growth factor (bFGF) in 162 patients with multiple myeloma (MM), 5 patients with Waldenström‘s macroglobulinaemia (WM), and 31 healthy controls. Among the MM patients there were 2 cases of primary plasma cell leukemia (PCL) and one case of extramedullary plasmacytoma. The levels of measured cytokines were correlated with the phase and stage of the disease as well as the most important clinical and laboratory parameters associated with disease activity (haemoglobin, creatinine, albumins, calcium, M‐component, CRP, β2m, LDH and bone involvement). We have found correlations between serum levels of angiogenic cytokines and some parameters depicting the disease activity and advancement. The serum level of VEGF in MM patients (median 244.5 pg\mL) correlated with serum concentrations of beta‐2‐microglobulin (β2m) greater than 2.5 mg\L (p ∓ 0.0005) and abnormal values of lactate dehydrogenase (> 425 U\L, median ‐‐ 329.0 pg\mL and < 210 U\L, median ‐‐ 426.6 pg\mL, p ∓ 0.004 and p ∓ 0.04 respectively). MM patients in stage III had higher serum levels of HGF (median ‐‐ 1 411.3 pg\mL) than those in stage I (median ‐‐ 1 219 pg\mL) (p ∓ 0.01) according to Durie and Salmon staging, and those in phase I (at diagnosis) (median 1 555.6 pg\mL) and phase III (in progression) (median 1 309.7 pg\mL) had higher levels than those in phase II (plateau phase) (median 1 047.9 pg\mL) (p ∓ 0.002 and p ∓ 0.02 respectively). Significantly elevated values of HGF were found in MM patients with anaemia (median ‐‐ 1 962.0 pg\mL) and hypercalcaemia (median ‐‐ 2 085.6 pg\mL) (p ∓ 0.00001 and 0.04 respectively). TGF‐β1 (median ‐‐ 33.9 ng\mL) correlated positively with high β2m values (> 2.5 mg\L) (p ∓ 0.04) and was significantly higher in phase I (median ‐‐ 40.1 ng\mL) than in phase II (median ‐‐ 30.9 ng\mL) (p ∓ 0.03) of the disease. The concentration of bFGF was significantly higher in stage III of MM (median ‐‐ 3.1 pg\mL) than in stage I (median ‐‐ 1.2 pg\mL) (p ∓ 0.04). We found that the survival probability was statistically higher for newly diagnosed MM patients with a concentration of VEGF lower than the median value for this cytokine. The concentrations of the cytokines analyzed in patients with Waldenström‘s macroglobulinaemia (WM), primary plasma cell leukaemia (PCL) and non‐secretory (NS) myeloma were not distinguishable from those found in MM patients. We also studied the relationship between the levels of cytokines analyzed and found positive correlations between bFGF and TGF‐β1 (ρ ∓ 0.183, p < 0.02), as well as VEGF and TGF‐β1 (ρ ∓ 0.537, p < 0.001) and VEGF and bFGF (ρ ∓ 0.197, p < 0.02). In conclusion, our data indicate a strong relationship between angiogenic cytokine serum levels and clinical course as well as selected laboratory parameters of patients with MM.