Endogenous thrombopoietin levels during the clinical management of acute myeloid leukaemia

Abstract

Thrombocytopenia represents a major problem in the management of acute myeloid leukaemia (AML). The data regarding the alterations of endogenous thrombopoietin (TPO) regulation during the clinical course of AML are limited. The aim of this study was to investigate endogenous TPO dynamics in association with platelets during the clinical course of AML. We serially measured both TPO and platelets concurrently over the entire treatment period of newly diagnosed patients receiving both remission induction and consolidation chemotherapies. The median concentration of TPO in AML patients at the initial diagnosis was 469.71 pg/ml and increased significantly during the aplastic period due to remission induction chemotherapy (median: 1085.33 pg/ml) but then decreased to a level (median: 45.26 pg/ml) encountered in the healthy control subjects (median: 56.90 pg/ml). In the cytopenic period due to consolidation treatment, TPO level again increased significantly to a high level (median: 891.38 pg/ml) during the platelet nadir, but decreased toward normal (median: 100.75 pg/ml) after the thrombocytopenic period had elapsed. In conclusion, endogenous TPO levels exhibit an inverse fluctuation in relation to platelet counts during the clinical course of AML. Pharmacological stimulation of thrombopoiesis in AML with novel molecules, including the recombinant thrombopoietins and the small peptide agonists, should be based on a critical administration strategy that must consider the endogenous levels of TPO. TPO levels in distinct AML disease states may explain the unsuccessful recombinant TPO trials and could help to design better strategies for ‘pharmacological stimulation of thrombopoiesis’ in AML.