Clinical and experimental studies in polycythemia vera and essential thrombocythemia

Sammanfattning: It is widely accepted that the diagnoses of polycythemia vera (PV) and essential throbocythemia (ET) are based upon the Polycythemia Vera Study Group criteria. These criteria are, however, of non-specific character and during the recent years more specific criteria have been proposed. In the present work the diagnostic potential of plasma erythropoietin (EPO), EPO-independent erythroid colony (EEC) growth, the stem cell antigen CD34 and thrombopoietin (TPO) were studied. The influence of different myelosuppressive agents on these variables was investigated.The concentration of CD34 positive (CD34+) cells was found to be significantly elevated in peripheral blood (PB) in PV patients compared to healthy controls. This difference was, however, not present in material from aspirated bone marrow (BM) or BM material obtained by biopsy. CD34+ cells were significantly elevated in PV patients with long disease duration and in patients with advanced disease. Also in PB of untreated ET patients CD34+ cells were significantly higher compared with controls.In vitro growth of EEC from BM progenitor cells was present in all PV patients studied. A majority of both PV and ET patients presented EEC growth when PB was used as a progenitor cell source.In all untreated PV patients the plasma EPO concentration was below the lower reference limit. About 50% of the untreated ET patients also had subnormal plasma EPO.No significant differences in plasma TPO concentrations were present when PV patients and healthy controls were compared. The mean plasma TPO concentration in ET patients significantly exceeded the mean for controls. The ET patients with subnormal plasma EPO had significantly lower plasma TPO compared with ET patients with normal or high plasma EPO. There was no significant difference between the ET patients with subnormal plasma EPO and controls.The mean plasma EPO did not rise above the lower reference limit when hemoglobin concentrations were normalized by phlebotomy treatment in PV patients. PV patients treated with different myelosuppressive agents, i.e. hydroxyurea (HU), radiophophorus (32P) or combinations of different cytostatics, presented significantly higher plasma EPO concentration compared with both untreated and phlebotomy treated PV patients. ET patients treated with HU, 32P, a-interferon or combinations of different cytostatics had significantly higher mean plasma EPO compared with untreated ET patients, also when correction for differences in hemoglobin levels were undertaken.PV patients on phlebotomy treatment only had higher concentrations of CD34+ cells and EEC growth compared with PV patients treated with HU. There was no significant difference in TPO concentration between PV on phlebotomy therapy and patients on myelosuppressive agents. Untreated ET patients had significantly higher CD34+ cell concentration and EEC growth compared with ET patients treated with HU. Untreated ET patients presented significantly lower plasma TPO concentrations compared with ET patients on myelosuppressive agents.Plasma EPO concentration should be used as a diagnostic criterion in the diagnosis of PV. Subnormal plasma EPO in ET is a valuable support for diagnosis and yields important information inasmuch as these patients have need for early initiation of myelosuppressive treatment due to high risk for vascular complications. EEC growth in PV and ET has good diagnostic potential and should be included as a diagnostic criterion. The concentration of CD34+ cells is not specific enough to be a diagnostic criterion in PV or ET but could be used as a proliferation marker in PV. Plasma TPO concentration can not be used as a diagnostic tool in PV or ET. There seems to be a relation between TPO and EPO in ET patients. ET patients with normal or high plasma EPO have high plasma TPO. In these patients TPO could even be the cause of platelet elevation.