Endogenous thrombopoietin serum levels during multicycle chemotherapy

Abstract

Summary.Little is known about the behaviour of endogenous thrombopoietin (TPO) serum levels during rapid sequences of dose-intensified chemotherapy. To characterize the relationship between TPO levels and platelet counts in this setting we serially measured both parameters over the entire treatment period of patients receiving multicycle polychemotherapy. We found TPO and platelet responses to be generally antagonistic through all cycles. However, a cross-correlation analysis indicated that TPO responses preceded platelet responses by approximately one day in all patients. The cumulative severity of thrombocytopenia observed over successive cycles was accompanied by an increasing TPO response which tended to grow overproportionally in relation to the degree of peripheral thrombocytopenia. These findings are consistent with a model suggesting that both platelet and megakaryocyte mass contribute to a receptor-dependent consumption process regulating the endogenous TPO level. In order to develop optimal schedules for exogenous TPO administration it might be important to consider endogenous TPO response characteristics.

Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma

“…In a paper from Lin et al, 26 the height of the rise in plasma TPO was proportional to the degree of thrombocytopenia, and in a group of patients maintaining a platelet count of greater than 100 ϫ 10 9 /L, the plasma TPO level was 266 Ϯ 231 pg/mL (not statistically different from healthy individuals). A second paper, from Engel et al, 7 measured the relationship between plasma TPO and platelets among a group of patients receiving different intensity chemotherapy for Hodgkin disease and found that the plasma TPO level ranged between 50 and 400, a value similar to the range we observed when the platelet count was above 100 ϫ 10 9 /L. Thus, the degree of rise in TPO was inversely related to the platelet count and did appear to be proportional to the effect observed by others with similar degrees of thrombocytopenia.…”

“…1,5 Reciprocal modulations of platelet counts and TPO are commonly observed in patients who receive myelosuppressive chemotherapy. [6][7][8][9][10] Platelet budding from megakaryocytes is a tightly regulated process that in part depends on activity of nuclear factor B (NF-B). 11 The kinetics of megakaryopoiesis are such that megakaryocyte differentiation often requires 10 days following cytotoxic drug treatment, and prolonged periods of thrombocytopenia are commonly seen following cytotoxic chemotherapy as a result of marrow injury.…”

Understanding cyclical thrombocytopenia: A mathematical modeling approach

“…To clarify this controversial point, Nagasawa et al (74) analyzed the relationship between the serum TPO level, platelet count, megakaryocyte and CFU-Meg number in a female patient whose megakaryopoiesis switched from ITP to amegakaryocytic phase during chemotherapy for lymphoma. They found (26), (55), (74), (87), (100)) argue that the megakaryocytes have a great importance in the regulation of thrombopoietin metabolism, and consider the observed time lag between the TPO and platelet response as a consequence of this fact (26). Kosugi 243.…”

High-dose chemotherapy as a consolidation approach in advanced ovarian cancer: long-term results

“…It is conceivable that the combined use of rh-GM-CSF plus rh-G-CSF could force progenitor commitment toward the myeloid lineage, removing progenitors from other hematopoietic lineages through a mechanism of in vivo progenitor competition. On the other hand, our observation that the serum levels of endogenous thrombopoietin, which has been reported to promote platelet rescue, 31 are significantly decreased in patients treated with three factors as compared with patients who received two cytokines or no factors at all is of interest (manuscript submitted).…”