Changes in endogenous TPO levels during mobilization chemotherapy are predictive of CD34(+) megakaryocyte progenitor yield and identify patients at risk of delayed platelet engraftment post-PBPC transplant

Patients with delayed platelet recovery post-PBPC transplant (PBPCT) are a high-risk group for thrombocytopenic bleeding and platelet transfusion depe ndence. Total CD34(+) cell dosage has been proposed as the most important f actor influencing the rate of platelet recovery. To achieve the shortest ti me to platelet engraftment, a minimum leukapheresis target of 10 x 10(6) CD 34(+) cells/kg was established for 30 patients. Of the 29 evaluable patient s, 62% had rapid (group I: time to platelets >20 x 10(9)/l less than or equ al to 10 days and 50 x 10(9)/l. less than or equal to 14 days) platelet rec overies while 38% had delayed (group II: 20 x 10(9)/l > 10 days and 50 x 10 (9)/l > 14 days) recoveries. Groups I and II were compared for: (1) pretrea tment variables; (2) mobilizing capability of CD34(+) cells and subsets inc luding megakaryocyte (Mk) progenitors; (3) infused dose of these cells at t ransplant; (4) changes in endogenous levels of Mpl ligand (or TPO) during m obilization and myeloablative chemotherapy, Group II patients received sign ificantly more platelet transfusions (6 vs 2.1, P = 0.002) post-PBPCT, had a higher proportion of patients with a prior history of BM disease (64% vs 6%, P = 0.001), and showed a reduced ability to mobilize differentiated (CD 34(+)/38(+), CD34(+)/DR+) and Mk progenitors (CD34(+)/42a(+), CD34(+)/61(+) ). Only the number of Mk progenitors reinfused at transplant was significan tly different between the groups (group II vs group I: CD34(+)/42a(+) = 1.0 2 vs 2.56 x 10(6)/kg, P = 0.013; CD34(+)/61(+) = 1.12 vs 2.70 x 10(6)/kg, P = 0.015). The ability to mobilize Mk progenitors correlated with percentag e changes in endogenous levels of TPO from baseline to platelet nadir durin g mobilization chemotherapy (CD34(+)/42a(+): 0.684, P = 0.007; CD34(+)/61(): r = 0.684, P = 0.007), with group II patients experiencing lower percent age changes. An inverse trend but no correlation was observed between seria l TPO levels and platelet counts. TPO levels remained elevated in group II patients throughout a prolonged period of thrombocytopenia (median days to 50 x 10(9)/l = 25 vs 11 for group I), indicating that delayed engraftment w as not due to a deficiency of TPO but to a lack of Mk progenitor target cel ls. Our results show that the number of reinfused Mk progenitors is a bette r predictor of platelet engraftment than total CD34(+) cell dosage, Small c hanges in endogenous TPO levels during mobilization predict for low Mk prog enitor yields.