Study of bone metabolism and angiogenesis in patients undergoing high-dose chemotherapy/autologous hematopoietic stem cell transplantation.

OBJECTIVES: As the interaction between hematopoietic stem cells (HSCs) and endosteal and endothelial niches in HSCs homing is essential, we aimed to study bone turnover and angiogenesis in 29 patients with lymphoma/multiple myeloma undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Serum samples were collected before high-dose chemotherapy (HDT), at the end of HDT, after HSC infusion, at the nadir of myelotoxicity, and at engraftment. Bone metabolism (CTX, TRACP-5b, bALP, OC, DKK1, RANKL, OPG), and angiogenesis (Ang1, Ang2) markers were measured. These markers were also measured in 21 control patients before and after conventional chemotherapy. RESULTS AND CONCLUSIONS: Bone resorption declined during HSCT (decrease in TRACP-5b [P < .001] and CTX [P = .006]). Bone formation declined as well (decrease in bALP and OC [P < .001 for both]). RANKL/OPG ratio, an indicator of osteoclastic activation, did not change significantly (P = .5). Ang1/Ang2 ratio, a vessel equilibrium marker, decreased significantly (P < .001) suggesting endothelial destabilization. The changes observed in the control group were similar except of bALP and RANKL/OPG ratio. Moreover, Ang1/Ang2 ratio on the day after HSC infusion strongly correlated with time to neutrophil and platelet engraftment (P < .001 for both). Conclusively, bone turnover and vessel destabilization represent important events during HSCT probably reflecting the effect of chemotherapy.

Protein Z (PZ) and plasminogen activator inhibitor-1 (PAI-1) plasma levels in patients with previously untreated Hodgkin lymphoma (HL).

PURPOSE: The role of Protein Z (PZ) in conditions, such as thrombosis, inflammation or cancer, is under investigation. Plasminogen Activator Inhibitor-1 (PAI-1) is an acute phase reactant that promotes thrombosis and tumorigenesis. Subject of this work was to study PZ and PAI-1 in patients with Hodgkin Lymphoma (HL), a malignancy with inflammatory background and relatively low incidence of thrombosis. METHODS: Newly diagnosed patients were enrolled in the study. Healthy individuals were used as controls. RESULTS: PZ levels were higher in patients compared to controls (not significantly), while PAI-1 levels were significantly higher in patients. Both PZ and PAI-1 concentrations did not correlate with most of patients' characteristics. Lower PZ levels at diagnosis were associated with presence of B symptoms and positive final positron emission tomography (PET) and higher baseline PAI-1 levels with positive final PET, too. PZ had a declining trend, but PAI-1 increased initially and decreased thereafter, during the treatment period. CONCLUSIONS: Conclusively, PAI-1, but not PZ, seems to be an acute phase protein in HL. Lower PZ and higher PAI-1 levels at diagnosis may be indicative of aggressive disease. These results need further verification.