Relatively rapid platelet recovery was previously observed in SAA patients (pts) post BMT (plt>50 x 109/L, day 20.6±5.5). We therefore studied the plasma levels of TPO and megakaryocyte ( M K ) colony stimulating activity (MK-CSA) as well as the number of circulating MK progenitors (CFU-MK) in 9 SAA pts on days -10 prior to BMT, on day 0 and on days 10, 20, 30, 40 and >80 post BMT. High endogenous TPO levels were detected by ELISA in all SAA pts prior to BMT (d-10) which were further escalated following conditioning with TLI/ CY (dO) (table). Very high TPO levels were sustained throughout the post BMT period in all patients tested. MK-CSA which reflects the thrombopoietic activity of TPO combined with endogenous cytokmes was determined by the capacity of the pts plasma to induce CFU-MK proliferation from healthy donor bone marrow (BM) cells. The plasma MK-CSA, was highly elevated prior to BMT, decreased to low levels immediately following conditioning on day 0, peaked again on day 20-30 post BMT in 7/9 pts, and gradually dropped to baseline activity by day >80 post BMT. Plasma concentrations of SCF, IL-3, and IL-6 were found to be < normal pre and post-BMT by ELISA. Circulating CFU-MK progenitors were not detected before day 20 post BMT. The average number of CFU-MK were 17.4 (range 0-50) and 47.5 (range S-110)/ 2 x 10s MNC at days 20 and 30 post BMT respectively. In conclusion, the facilitated platelet engraftment seen in SAA following BMT may be related to the high plasma level of TPO which is sustained throughout the entire transplant period. TPO may synergize with other endogenous cytokines, such as Flt-3 ligand which is known to be high in SAA patients, to support thrombopoiesis. days -10 0 10 20 30 40 50 80 TPO mean 1129 2141 1427 1547 1430 734 601 193 range 508- 1246- 602- 682- 136- 240- 195- 69- na/mL 1904 3107 2194 2534 2315 1404 1588 482.
|Number of pages||1|
|State||Published - 1998|