FOLLOW-UP OF PLASMA FLT3 LIGAND CONCENTRATION IN HEMATOPOIETIC STEM CELL TRANSPLANTED PATIENTS.
J.M. Bertho, M. Prat, J. Frick, J.P. Laporte, N.C. Gorin, D. Thierry. European Radiation research 2004, the annual congress of the european society for radiation, 25-28/08/2004, Budapest, Hongie.
Objectives: Previous works indicated that Flt3 ligand (FL) concentration was inceased in patients suffering from aplasia either acquired (such as aplastic anemia or fanconi anemia) or induced by chemotherapy, suggesting a possible use of FL as a biological indicator of bone marrow aplasia. The aim of the present work was to follow-up variations in plasma FL concentration during radiation or chemotherapy induced aplasia, in order to compare the influence of conditioning regimen on FL concentration modifications and to define the role of circulating cells in the regulation of FL during aplasia. Material and methods: 10 patients undergoing conditioning regimen including BEAM, cyclophosphamide + total body irradiation (TBI) or cyclophosphamide + anti-lymphocyte serum (ALS) and followed by haematopoietic stem cell transplantation were enrolled in this study. Plasma FL concentration was measured by ELISA, membrane-bound form of FL (mFL) on the surface of circulating white blood cells (WBC) was determined by FACS analysis and FL mRNA expression in WBC by RT-PCR. Results: We showed that FL concentration increased rapidly during conditioning regimen in all patients. At any time point, FL concentration was negatively correlated with the number of WBC. Area under the curve (AUC) of FL according to the time was directly correlated with the duration of aplasia, indicating that blood FL concentration was a reflect of aplasia. However, in ALS treated patients, a reduction of FL AUC was observed. This reduction was due to a rapid decrease of blood FL concentration down to normal values, before the WBC recovery. As a consequence, FL AUC did not correlate with duration of aplasia. Conclusion: Our results indicate that FL concentration variations in the blood are the reflect of either radiotherapy- or chemotherapy-induced aplasia. Moreover, these results showed that the regulation of FL concentration in the blood of patients by WBC is mainly implicated during the recovery period of aplasia.