Serum Levels of Endogenous Thrombopoietin and Granulocyte-Colony Stimulating Factor in Patients with Acute or Lymphoma Type Adult T-cell Leukemia During Multicycle Chemotherapy

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Abstract
Recent multidrug chemotherapy for adult T-cell leukemia (ATL) showed improved findings, however, these protocols often induced persistent myelosuppression. Among 67 patients with acute and lymphoma type ATL treated between January 1996 and December 1998, 42 patients died during this period and showed chemotherapy-induced myelosuppression. To characterize the relation between the severity of myelosuppression and the endogenous thrombopoietin (TPO) or granulocyte-colony stimulating factor (G-CSF) levels in ATL patients, we measured these hematopoietic factors using ELISA method. Nineteen patients with acute or lymphoma type ATL and 16 healthy individuals were examined. During thrombocytopenia, the serum TPO levels were significantly higher than that of controls (P < 0.0001) and were inversely correlated with the platelet counts (r = -0.687 P < 0.001). Later in the chemotherapy cycle, severe persistent thrombocytopenia occurred and TPO levels elevated and remained at a high level approximating the TPO levels of exogenous TPO administration (0.3 microg/kg body weight). On the other hand, the serum G-CSF levels with absolute neutrophil counts (ANC) below 0.5 x 10(9)/L were significantly higher than controls (P = 0.009) and inversely correlated with ANC (r = -0.382 P = 0.0034). However, G-CSF levels in six samples obtained after 6 h of G-CSF (100-150 microg per body) administration was approximately 50-fold higher than that in the neutropenic states. These findings suggested that G-CSF can effectively reduce the severity and duration of intensified chemotherapy-induced neutropenia and higher dose exogenous TPO (higher than 0.6 microg/kg per day) therapy may be required to enhance platelet recovery after intensive chemotherapy in ATL patients.