Endothelial cell markers in bone marrow transplant recipients with and without acute graft-versus-host disease

Abstract

Summary:and capillary leak syndrome. Microangiopathy, a characteristic form of EC damage associated with severity of GVHD in recipients of allogeneic bone marrow transplants, has To investigate endothelial cell alterations in BMT recipients developing acute graft-versus-host disease been described earlier by our group 1,2 suggesting that not only the epithelium but also EC may be affected in the (aGVHD) we determined levels of the endothelial cell markers von Willebrand factor (VWF) and thrombomcourse of aGVHD. In these studies, von Willebrand factor (VWF) levels odulin (TM) in 57 patients undergoing BMT. Before conditioning VWF and TM levels did not differ signifiwere used as markers of EC damage. VWF can be synthesized and released by EC and is regarded as an indicator cantly between transplant recipients who later developed no or mild (grade I) aGVHD (group A, alloof EC activation or injury. 3 TM which is localized on the surface of EC plays a crucial role in the activation of the geneic n ‫؍‬ 22, autologous n ‫؍‬ 7; VWF 136.0 ؎ 44.1%; TM 29.5 ؎ 18.0 ng/ml), and those with moderate or sevnatural anticoagulant protein C. 4 TM, therefore, is an important factor for the maintenance of the antithrombotic ere (grade II or III) aGVHD (group B, n ‫؍‬ 28; VWF 142.2 ؎ 37.6%; TM 35.2 ؎ 20.1 ng/ml). A first signifiproperties of EC. A soluble form of TM, which probably represents a degradation product of tissue TM, can be cant rise of both VWF and TM levels was noted after conditioning (day 0) both in group A (VWF measured in plasma and represents a reliable marker of EC damage. 5-8197.0 ؎ 113.3%; P Ͻ 0.001; TM 39.3 ؎ 23.3 ng/ml; P Ͻ 0.01) as well as in group B (VWF 201.7 ؎ 53.3%; P We have now determined VWF and TM levels in the plasma of BMT recipients to evaluate further the possible Ͻ 0.0001; TM 43.5 ؎ 23.5 ng/ml; P Ͻ 0.05). Subgroup analysis of autografted patients revealed no significant association of acute GVHD and endothelial cell injury. increase after conditioning in these patients. At the time of engraftment and onset of aGVHD (day 21), when VWF and TM levels within the groups were signifiPatients, materials and methods cantly elevated as compared with baseline (day −8) levels, group B patients (62.7 ؎ 38.5 ng/ml) had signifiFifty-seven patients (mean age 37.1 Ϯ 10.2 years; range from 16 to 58 years; 25 female, 32 male) suffering from cantly higher (P Ͻ 0.01) TM levels than patients of group A (37.4 ؎ 19.6 ng/ml). This significant elevation hematologic diseases were studied. Diagnoses included AML (n = 18), ALL (n = 9), CML (n = 26), lymphoma (n also persisted at the end of the investigational period (day 28; group B: 56.0 ؎ 37.6 ng/ml; group A:= 2), multiple myeloma (n = 1), and SAA (n = 1). Fifty patients received allogeneic transplants (33 from related, 17 38.2 ؎ 23.7 ng/ml; P Ͻ 0.01). An elevation of endothelial cell markers is found in the course of BMT, particularly from unrelated donors), seven patients autologous transplants. The following conditioning regimens were used: after conditioning and at the...

Serial evaluation of the oncological pediatric risk of mortality (O-PRISM) score following allogeneic bone marrow transplantation in children

“…24 In addition, conditioning treatment may significantly affect the complement system and coagulation parameters, thereby provoking severe acute complications such as VOD and capillary leakage syndrome. 22,25,27,28 Our analysis of the O-PRISM score demonstrates the early prognostic impact of the O-PRISM score and thus provides evidence that these experimental observations may be of significant clinical relevance. In addition, the O-PRISM score may help to identify a group of high-risk patients early who may benefit from alternative supportive strategies.…”

The role of the endothelium in the short-term complications of hematopoietic SCT

“…Zeigler et al 20 observed that VWF and TM were increased in all patients with TAM after HSCT. Salat et al 21 evidenced that VWF and TM rose significantly after conditioning in all patients. At the time of engraftment or at the onset of GVHD, VWF and TM levels were significantly increased with respect to the baseline, especially in patients with acute GVHD grades II-IV, suggesting that ECs could be injured.…”

Serum levels of soluble adhesion molecules in stem cell transplantation-related complications

“…TMA, a characteristic form of endothelial cell damage, has been associated with acute GVHD, cytotoxic drugs, irradiation, and viral infections such as cytomegalovirus and human herpesvirus-6 in patients with BMT. [1][2][3][4][5] It is well known that damage or activation of vascular endothelial cells, mediated by cytokines such as interleukin-1 or tumor necrosis factor-␣, induces expression of vascular adhesion molecules, ie intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin, on their cell surface. 6 This process appears to be important in the recruitment of leukocytes to the site of inflammation.…”