Hypereosinophilic syndrome associated with polycythemia vera

A 60-year-old woman presented with relapse of polycythemia vera associated with hypereosinophilic syndrome (HES) with abnormal immunologic measures, including increased serum IgE and IgG levels, high levels of circulating immune complexes, rheumatoid factor, and antinuclear antibodies. Treatment with hydroxyurea was followed by a dramatic response of both the polycythemia vera and the HES, with return to normal of the abnormal immunologic measures. This case report documents that evidence of immunologic and myeloproliferative causes of HES may coexist in the same patient.     

Busulfan in patients with polycythemia vera or essential thrombocythemia refractory or intolerant to hydroxyurea

Therapeutic options for patients with polycythemia vera (PV) and essential thrombocythemia (ET) resistant or intolerant to hydroxyurea are limited. Busulfan is effective as first-line therapy, but there is scarce information on this drug as second-line treatment. The efficacy of busulfan in patients with advanced PV or ET refractory or intolerant to hydroxyurea was assessed in 36 patients (PV n?=?15, ET n?=?21) treated for a median of 256 days. Complete hematological response (CHR) was achieved in 83 % of patients, after a median time of 203 days (range 92–313). The probability of sustained CHR at 1 and 2 years was 87 and 62 %, respectively. Time to CHR was shorter in patients treated with ≥14 mg of busulfan per week than with lower doses (141 versus 336 days, p?=?0.01). Partial molecular response was achieved in three out of nine (33 %) patients. Busulfan was stopped in 27 patients (75 %) due to CHR achievement in 18 cases (67 %), hematological toxicity in 8 cases (30 %), and disease transformation in 1 case. With a median follow-up of 721 days, six patients have died, with the probability of survival at 2 years being 85 %. The probability of thrombosis at 2 years was 11 %. Transformation into acute leukemia or myelodysplastic syndrome was observed in three cases, all of them in a JAK2V617F-negative clone carrying additional mutations. Busulfan, at a dose of 2 mg/day, is an effective option for elderly patients with PV or ET who fail to hydroxyurea, but a significant rate of transformation was observed.     

Alpha-interferon in polycythemia vera and essential thrombocythemia

Twenty-one patients with chronic myeloproliferative disorders, eleven with polycythemia vera (PV) and ten with essential thrombocythemia (ET), were treated with small doses of alpha-2a interferon (IFN). The median follow-up was, respectively, 10.8 months (range 4-22) for PV and 8.11 months (range 4-16) for ET. Six patients with PV and five with ET had been previously treated with conventional cytotoxic drugs, while the remaining patients were newly diagnosed. In four patients with PV we observed a durable normal hematocrit level (PCV less than 0.48) and a reduction of platelet count and spleen size within 4-8 weeks of treatment. Three patients achieved moderate disease control. In the others the disease remained substantially unchanged. Five out of nine evaluable patients with ET showed complete response (CR) within six weeks, one patient had a partial response (PR) and three no response (NR). In one patient with ET the IFN therapy was stopped after twelve days because neurological side effects were observed. All the other patients tolerated long-term treatment very well.     

Myelodysplastic syndrome with trisomy 11 associated with polycythemia vera

A 52-year-old male with myelodysplastic syndrome (MDS) who had a prior history of polycythemia vera is reported. Chromosome analysis revealed that the bone marrow and blood cells at the MDS phase contained trisomy of chromosome 11 as the sole cytogenetic change. Trisomy 11 is rarely found in hematologic neoplasia, and all of the reported cases with trisomy 11 were diagnosed as having nonlymphocytic neoplasia. In this report, a correlation between the chromosome change and leukemia/MDS developed in polycythemia vera is discussed.     

Front-line therapy in polycythemia vera and essential thrombocythemia

Because the current therapy in polycythemia vera (PV) and essential thrombocythemia (ET) is aimed at lowering the risk of thrombosis, the risk classification system in these disorders is shaped according to thrombotic risk. Patients with either PV or ET can be stratified in a "high-risk" or "low-risk" category according to their age and previous history of thrombosis. Whether novel risk factors such as leukocytosis and JAK2 mutation may be included in the prognostic stratification requires confirmation in prospective future clinical studies. The identification and appropriate management of cardiovascular risk factors and the promotion of a healthy lifestyle in chronic myeloproliferative neoplasms (MPN), as in the general population, should be considered a cornerstone of vascular prevention. Blood hyperviscosity in PV is a major cause of vascular disturbances which severely impact on morbidity and mortality. An aggressive target of hematocrit lower than 45% in males and 42% in females has been advised by the European LeukemiaNet (ELN) group, although no convincing evidence of this recommendation is currently available. The efficacy and safety of low-dose aspirin (100mg daily) in PV has been assessed in the European Collaboration on Low-dose Aspirin in Polycythemia (ECLAP) double-blind, placebo-controlled, randomized clinical trial. Translating evidence from the positive results of ECLAP to ET may be questionable. The most commonly used front-line therapy drugs for the treatment of high-risk PV and ET patients include hydroxyurea and alpha-interferon at any age while anagrelide is recommended as second line-therapy in resistant and intolerant ET patients. Busulphan is a front-line therapy in the elderly. By definition, children with ET are a population with low vascular risk unless a major thrombotic or hemorrhagic event has occurred. ELN recommends to prescribe cytoreductive drugs in children as a last resort. No results of clinical trials with JAK-2 inhibitor drugs in PV and ET are so far available.     

Anagrelide-associated cardiomyopathy in polycythemia vera and essential thrombocythemia

A comprehensive database inquiry at our institutions identified 11 patients with echocardiogram-documented idiopathic cardiomyopathy that post-dated a diagnosis of either polycythemia vera or essential thrombocythemia. Anagrelide therapy was temporally associated with the particular complication in 6 patients, all of whom experienced symptomatic and/or objective improvement after drug discontinuation.     

Platelet density in essential thrombocythemia and polycythemia vera

This study aims to compare platelet density in myeloproliferative disorders (essential thrombocythemia (ET) and polycythemia vera (PV)) with platelet density of healthy subjects. Platelet density peaks were determined using a specially designed apparatus for scanning light transmission variations along test tubes containing density-separated platelets. Eighteen patients with myeloproliferative disorders (nine ET and nine PV) were compared with a control group consisting of 12 healthy volunteers. Compared with healthy volunteers, patients with myeloproliferative disorders had significantly lower platelet peak density ( P< 0.001). It is concluded that determination of peak platelet density may be a useful tool for excluding ET and PV. A high platelet density peak makes a clonal disorder less likely and a low density peak would confirm the suspicion.     

Platelet density in essential thrombocythemia and polycythemia vera

This study aims to compare platelet density in myeloproliferative disorders (essential thrombocythemia (ET) and polycythemia vera (PV)) with platelet density of healthy subjects. Platelet density peaks were determined using a specially designed apparatus for scanning light transmission variations along test tubes containing density-separated platelets. Eighteen patients with myeloproliferative disorders (nine ET and nine PV) were compared with a control group consisting of 12 healthy volunteers. Compared with healthy volunteers, patients with myeloproliferative disorders had significantly lower platelet peak density ( P< 0.001). It is concluded that determination of peak platelet density may be a useful tool for excluding ET and PV. A high platelet density peak makes a clonal disorder less likely and a low density peak would confirm the suspicion.     

Leukocyte-platelet interaction in patients with essential thrombocythemia and polycythemia vera

OBJECTIVE: Circulating polymorphonuclear leukocyte (PMN) activation occurs in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We want to define whether this phenomenon plays a role in the formation of circulating PMN-platelet aggregates in these conditions. METHODS: In 80 patients (46 ET and 34 PV) and 50 control subjects, we conducted a flow cytometric analysis to evaluate the levels of PMN-platelet aggregates (defined as the percentage of CD11b-positive PMN coexpressing a platelet-specific marker, i.e., CD42b or CD62P) and the levels of activated PMN and activated platelets. In addition, the in vitro PMN-platelet aggregate formation in response to N-formyl-methionyl-leucyl-phenylalanine (f-MLP)-induced activation of PMN was studied. RESULTS: Significantly high PMN-platelet aggregates in ET and PV patients were found and were associated with increased PMN surface CD11b and surface platelet CD62P expression. In vitro f-MLP stimulation upregulated PMN-CD11b expression and simultaneously increased CD11b/CD42b and CD11b/CD62P aggregates, without affecting platelet surface antigens. In ET patients receiving aspirin, the increments in f-MLP-induced PMN-CD11b and in PMN-platelet aggregates were significantly lower versus ET subjects not treated with aspirin. CONCLUSION: Our data show that in ET and PV patients PMN activation plays an important role in increasing circulating PMN-platelet aggregates and suggest that aspirin treatment may decrease their formation.     

The rate of progression to polycythemia vera or essential thrombocythemia in patients with erythrocytosis or thrombocytosis

The clinical relevance of mild erythrocytosis (hematocrit > 0.48 in women or > 0.51 in men) or thrombocytosis (platelet count > 400 x 10(9) cells/L) in asymptomatic persons is uncertain.     

Risk-adapted therapy in essential thrombocythemia and polycythemia vera

The clinical course of Polycythemia vera (PV) and Essential Thrombocythemia (ET) is marked by an high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of PV and ET transformation into acute leukemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients with PV should be treated with phlebotomy and low-dose aspirin, whereas those with ET can be left untreated. Cytotoxic therapy is indicate in high-risk patients and the drug of choice is hydroxyurea because its leukemogenicity is low, if any. New therapeutic options, theoretically devoid of leukemic risk, such as alpha-interferon, anagrelide and imatinib should be reserved to selected patients and require further clinical experience.     

Differentiation between essential thrombocythemia and polycythemia vera with marked thrombocytosis

Accurate distinction between essential thrombocythemia and thrombocytotic polycythemia vera requires determination of the red cell mass in the presence of adequate iron stores, but this is not always possible. We therefore compared the clinical and laboratory features at the time of presentation of 50 patients with unequivocal essential thrombocythemia and 27 patients with thrombocytotic polycythemia vera. Univariate analysis failed to identify any single parameter capable of reliably separating the groups. A logistic regression algorithm incorporating hematocrit, white cell count, and spleen size markedly increased the diagnostic accuracy (92%) compared with predictions based on the hematocrit alone (52%). The algorithm's usefulness for patients with intermediate hematocrits was confirmed by analysis of independent samples of essential thrombocythemia and thrombocytotic polycythemia vera patients, and also by analysis of patients with probable essential thrombocythemia in whom the diagnosis could not be confirmed because of inadequate exclusion of polycythemia vera. Furthermore, comparison of survival data suggests that differentiating these disorders is prognostically important. The algorithm is recommended as an alternate method for differentiating essential thrombocythemia from thrombocytotic polycythemia vera whenever the red cell mass is unavailable or iron deficiency cannot be excluded.     

A clinical update in polycythemia vera and essential thrombocythemia

Polycythemia vera and essential thrombocythemia pose specific management issues that distinguish them from other chronic myeloproliferative disorders. They are associated with a better prognosis, as well as a variable risk of thrombohemorrhagic complications. In addition, essential thrombocythemia occurs comparatively more often in young people and women. Treatment strategies for patients with polycythemia vera and essential thrombocythemia must consider the possibility of long-term survival, morbidity from thrombotic complications, transformation into myelofibrosis with myeloid metaplasia or acute myeloid leukemia, and the effect of specific therapies on the incidence of leukemic transformation and on pregnancy. There is increasing concern about the possible leukemogenic effect of hydroxyurea. Newer therapeutic agents, including interferon alpha and anagrelide, are being used more often. Ongoing studies are reexamining the effects of low-dose aspirin in preventing thrombotic complications.     

Red cell mass measurement in patients with clinically suspected diagnosis of polycythemia vera or essential thrombocythemia

The cut off for hemoglobin or hematocrit that indicates the need for an isotopic red cell mass study was investigated in 179 patients with a presumptive diagnosis of polycythemia vera or essential thrombocythemia. Hematocrit showed better diagnostic accuracy than hemoglobin. Hemoglobin over 18.5 g/dL in males or over 16.5 g/dL in females showed a high specificity indicating that red cell mass study could be avoided in such cases, but it showed low sensitivity leading to 46% false negatives. The best value of hematocrit to indicate a red cell mass study was 0.50 L/L in males (specificity 75%, sensitivity 87.5%) and 0.48 L/L in females (specificity 73%, sensitivity 94%). Lowering the hematocrit threshold to 0.48 L/L in males increased sensitivity up to 95%. A red cell mass study should be performed in patients with suspected diagnosis of essential thrombocythemia or polycythemia vera and with hematocrit between 0.48 L/L and 0.52 L/L.Key words: polycythemia vera, essential thrombocythemia, red cell mass, hemoglobin, hematocrit     

Initial (latent) polycythemia vera with thrombocytosis mimicking essential thrombocythemia

Patients have previously been described who showed clinical signs and symptoms suggesting essential thrombocythemia (ET), but later transformed to polycythemia vera (PV). From a series of 344 patients with a sustained borderline to moderate erythrocytosis, 44 failed to conform initially with the diagnostic criteria of the WHO for PV, because of their low hemoglobin level. Twenty-three patients of this group presented with a thrombocytosis exceeding 600 x 10(9)/l and therefore suggested ET, but later developed full-blown PV. For comparison we investigated also 164 patients with manifest PV, 90 patients with ET and 22 patients with reactive thrombocytosis (Th). The histopathology of initial PV was evaluated by stepwise discriminant analysis of 17 standardized features. Quantity and left shifting of erythro- and granulopoiesis, giant forms and naked nuclei of megakaryocytes, cellularity and reticulin fibers proved to exert a significant relevance concerning differentiation from true ET and Th. In conclusion, initial PV with thrombocytosis is characterized by a special pattern of BM histopathology. Therefore, so-called masked PV in patients with ET or simultaneous PVR-1 gene expression and endogeneous erythroid colony growth in ET patients are probably in keeping with initial PV mimicking ET.