Thrombopoietin concentrations in peripheral blood correlated with platelet numbers in two patients with thrombocytopenia by chronic graft‐versus‐host disease

Abstract

Thrombocytopenia is well known to be one of the clinical manifestations of chronic graft-versus-host disease (cGVHD). However, there exist cases in which the cause of thrombocytopenia has been unexplained. Recently, thrombopoietin (TPO) from bone marrow (BM) stromal cells and transforming growth factor (TGF)-␤ from platelets and megakaryocytes have been identified as strong positive and negative regulators of megakaryopoiesis in vivo. We hypothesized that the decreased TPO production from BM could be one of the causes of thrombocytopenia in the patients with cGVHD. In the present study, therefore, TPO and TGF-␤ concentrations in peripheral blood (PB) and BM were measured serially in two patients with acute leukemia who had received fully matched stem cell transplantation from relatives and subsequently developed extensive cGVHD with thrombocytopenia. The results showed that platelet numbers correlated well with the TPO concentrations, which were consistently higher in BM than in PB. The difference in TPO concentrations between BM and PB was decreased when the platelet levels were low, indicating that the amount of TPO production from BM decreased throughout the duration of thrombocytopenia. TGF-␤ concentrations were normal during all periods in which measurements were carried out. Thus, our results suggest that one mechanism of thrombocytopenia in patients with cGVHD is low TPO production by BM cells. Am. J. Hematol. 73:285-289, 2003.

Inhibiting TGF-beta signaling preserves the function of highly activated, in vitro expanded natural killer cells in AML and colon cancer models

“…Circulating TGF-beta levels ranging from 5ng/ml to >20ng/ml have been described in both hematologic malignancies and solid tumor patients [ 19 – 23 ]. These levels are higher than seen in healthy volunteers and correspond with impaired cellular immunity [ 16 – 19 , 24 – 26 ]. Levels below 1ng/ml have been described in the peripheral blood and bone marrow of healthy volunteers [ 24 ] while acute myeloid leukemia and myelodysplastic syndrome patients have levels ranging from 6 to 42ng/ml [ 21 ].…”

“…These levels are higher than seen in healthy volunteers and correspond with impaired cellular immunity [ 16 – 19 , 24 – 26 ]. Levels below 1ng/ml have been described in the peripheral blood and bone marrow of healthy volunteers [ 24 ] while acute myeloid leukemia and myelodysplastic syndrome patients have levels ranging from 6 to 42ng/ml [ 21 ]. In a study of 45 colorectal cancer patients, Narai et al reported circulating total TGF-beta levels greater than 15ng/ml in patients with metastatic disease [ 20 ].…”

Chronic graft versus host disease

“…Thrombocytopenia at the time of chronic GvHD diagnosis has been associated with a poor prognosis (Sullivan et al , 1988a; Anasetti et al , 1989; Akpek et al , 2001a). Peripheral blood thrombopoietin concentrations may be decreased secondary to BM stromal cell damage (Hirayama et al , 2003). Eosinophilia may be seen and may be an indicator of chronic GvHD activity.…”

Thrombocytopenia and hemostatic disorders in chronic graft versus host disease

“…Thrombocytopenia because of low thrombopoietin (TPO) level is generally thought to be relatively rare; however, it has not been thoroughly investigated in the cGVHD setting. Hirayama et al 83 described two cGVHD patients with low platelet counts and strong correlations of platelet and megakaryocyte numbers with TPO concentrations in peripheral blood. They concluded that low TPO production may be responsible for thrombocytopenia in some cGVHD patients.…”