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The Philadelphia chromosome-negative (Ph-) chronic myeloproliferative neoplasms include the three well-known clinical entities polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Over time, patients with ET and PV may develop myelofibrosis (MF), and all three entities carry a risk of transformation into acute myeloid leukemia (AML). In a population-based survey during 1983-1999, we studied a total of 358 patients who were diagnosed with ET and PV in the city of Gothenburg, Sweden. At the time of diagnosis, evaluable bone marrow biopsy material was available from 280 of these patients. The current work was aimed at investigating the impact of peripheral blood counts, spleen size, and bone marrow biopsy findings at diagnosis on long-term survival and the risk of development of AML or MF in this well-defined unselected population. The variables evaluated were venous blood hemoglobin concentration, packed cell volume, white blood cell count, platelet count, and splenic enlargement; as to bone marrow biopsies, interest was focused on reticulin content, focal or generalized collagen formation, bone marrow cellularity, and megakaryocyte profile number. Over the median observation time of 15 yr, the patients with ET did not demonstrate any significant difference as to survival compared to the normal Swedish population (hazard ratio, 1.23; 95% confidence interval, 0.97-1.51; p= 0.089). The patients with PV, on the other hand, had a significantly shorter survival compared to general population (hazard ratio, 1.66; 95% confidence interval, 1.38-1.99; p< 0.001). A lower hemoglobin concentration at diagnosis of ET predicted poorer survival (p =0.0281), whereas patients with PV with splenic enlargement at diagnosis had a shorter survival (p =0.037). In the patients with ET, the risk of transformation to either MF or AML was significantly associated with low hemoglobin concentration and high white cell count at diagnosis (p =0.0037 and 0.0306, respectively). An increased reticulin content and hypercellularity in the bone marrow at diagnosis were also independent risk factors (p =0.0359 and 0.0103, respectively). The risk of transformation in patients with PV was significantly associated with splenic enlargement and increase in bone marrow reticulin content (p =0.0028 and 0.0164, respectively)., (© 2010 John Wiley & Sons A/S.)

Approximately 45% of newly diagnosed patients with essential thrombocythaemia (ET) demonstrate subnormal plasma erythropoietin (EPO) concentrations, which constitutes a risk factor for occlusive vascular events. In 58 ET patients, a possible association between polycythaemia rubra vera-1 (PRV-1) overexpression and subnormal plasma EPO was investigated, which was always measured prior to the institution of platelet lowering agents. At the time when PRV-1 expression was measured, 28 of 58 (48%) ET patients had received platelet lowering treatment. PRV-1 expression was measured by quantitative real-time reverse transcription-polymerase chain reaction assay of mRNA extracted from purified peripheral blood buffy coat. The cycle threshold (CT) value of PRV-1 was determined and was divided with the CT value for the housekeeping GAPDH gene transcript. A quotient <0.93 was defined as PRV-1 positive. Of the ET patients 12 of 58 (21%) were PRV-1 positive and 19 of 58 (33%) demonstrated subnormal plasma EPO. In the 58 ET patients there was a significant association between low plasma EPO and PRV-1 positive results (P = 0.001). The 30 ET patients who had not received any platelet lowering treatment showed a significant (P = 0.005) relation between PRV-1 positivity and subnormal plasma EPO. No such relationship was present in the 28 ET patients who had received prior treatment with the above drugs (P = 0.147).

It has been shown previously that measurement of the spleen size and plasma erythropoietin (EPO) concentration are valuable adjuncts in the diagnostic work-up of patients with polycythaemia vera. The aim of the present work was to evaluate their value in the assessment of apparent polycythaemia (AP). Therefore, over a 24-month period we routinely performed bone marrow biopsies, measurement of red cell mass (RCM) and plasma volume (PV), spleen size determination by gamma camera scintigraphy and determination of the plasma EPO concentration in consecutive patients referred to us because of elevated values for packed cell volume (>0.48 in females and >0.51 in males). After having excluded patients with clonal and secondary polycythaemias we were left with 38 patients (27 males and 11 females) with AP. In all of them the measured RCM was within normal range, i.e. <36 ml/kg for males and <32 ml/kg for females. The subjects were characterized by moderate increase in RCM and a concomitant moderate decrease in PV. Thus, as an average the measured RCM exceeded the predicted values by 14% in males and by 12% in females; conversely, as compared to the predicted values the average measured value for PV was reduced by 17% in males and by 8% in females. The average RCM for males was 29+/-3 ml/kg; the corresponding figure for females was 23+/-4 ml/kg. It was shown that 86% of the subjects had plasma EPO concentrations within the control range; the remaining had values slightly above or below the control range. The mean posterior spleen scan area was 57+/-16 cm2 and mean left lateral area 57+/-17 cm2; the reference value for spleen scan area (for both projections) is 57+/-12 cm2. Of the patients 35/38 (92%) had a spleen scan area within the mean+2SD for controls and 38 subjects (100%) had values within the mean+3SD. It is concluded that measurement of plasma EPO and a careful assessment of the spleen size should always be considered in the evaluation of patients with elevated values for venous packed cell volume.