Markers of endothelial function in pediatric stem cell transplantation for acute leukemia.
BACKGROUND
Endothelial cells and leukocytes intimately interact in inflammation and coagulation processes, so that dysregulation of their function may lead to both cellular damage and thrombosis, which may occur as complications of bone marrow transplantation (BMT). Partially conflicting evidence about endothelial markers and their relationships with clinical complications after BMT has been reported in the literature. Since almost all studies were carried out in adults, we evaluated some recent available markers of endothelial cell function in pediatric patients undergoing stem cell transplantation (SCT) for acute leukemia.


METHODS
We studied the variation in circulating serum endothelial-selectin (ES), leukocyte-selectin (LS), thrombomodulin (TM), von Willebrand factor (vWF), nitrate + nitrite (NO(2) (-)/NO(3) (-)), endothelin-1 (EN), and tissue factor (TF) in 21 pediatric patients undergoing SCT for acute leukemia.


RESULTS
ES and LS significantly lowered following SCT and returned to pre-SCT levels 4 weeks after the procedure. NO(2) (-)/NO(3) (-) markedly increased following SCT. Also, TM and vWF increased, although such changes did not reach statistical significance. EN and TF did not appreciably change. A strong correlation was observed between white blood cell (WBC) count and both ES and LS, as well as between such selectins. TM significantly correlated with both selectins and NO(2) (-)/NO(3) (-). The pre-conditioning levels of TM and vWF in patients undergoing major complications, considered altogether, were significantly lower and higher, respectively, than in uncomplicated patients. NO(2) (-)/NO(3) (-) levels 3 and 4 weeks post-SCT were significantly lower in patients suffering from veno occlusive disease. Both selectins were significantly higher in allo- than in auto-transplanted patients 4 weeks after SCT.


CONCLUSIONS
Our data support the hypothesis of severe endothelial damage after conditioning and SCT, particularly allogeneic. However, the increase in TM, which has strong anticoagulant properties, and metabolites of NO, involved also in protective actions, may reflect regeneration of the anti-thrombotic endothelial function. This could take place after transitory functional impairment, rather than pure endothelial damage.
Luzzatto
Guido
G
Department of Medical and Surgical Science, Chair of Hematology, Padova University Medical School, Italy.
Cella
Giuseppe
G
Messina
Chiara
C
Randi
Maria Luigia
ML
Sbarai
Alessandra
A
Zanesco
Luigi
L
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000628:therapy*; D019087:Selectins / Q000097:blood; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D018180:Thrombomodulin / Q000097:blood; D013997:Time Factors; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D019332:Endothelin-1; D009566:Nitrates; D009573:Nitrites; D019087:Selectins; D018180:Thrombomodulin; D014841:von Willebrand Factor; D009569:Nitric Oxide