Search

Objectives: Polycythemia vera (PV) is an acquired clonal hematopoietic stem cell disorder characterized by the overproduction of red blood cells. It has long been underlined that there are differences in treatment patterns in routine practice. Therapeutic strategies have also expanded, and in recent years the JAK1/JAK2 inhibitor ruxolitinib has emerged as a second-line therapeutic option in patients who are intolerant to or resistant to hydroxyurea. Determining the impact of changes on practice patterns is of interest, especially for aspects that lack detailed guidance for management., Methods: To gain insights into treatment patterns by clinicians treating patients with PV in Italy, we carried out a survey of 60 hematologists and transfusion specialists. The questions covered: treatment of low-risk patients, definition of significant leukocytosis, splenomegaly and excessive phlebotomies, resistance/intolerance to hydroxyurea, use of ruxolitinib, cytoreductive therapy, and vaccines., Results: In general, the results of the survey indicate that there is a large heterogeneity in management of patients with PV across these areas., Conclusions: While helping to provide greater understanding of treatment patterns for patients with PV in Italy, our survey highlights the need for additional clinical studies to obtain more precise guidance for the routine care of patients with PV., (© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Objectives: Pregnancies in women with polycythemia vera (PV) are associated with an increased risk of PV-related maternal complications and often result in miscarriage. Recommendations for the management of PV pregnancies are mainly based on studies with a small number of patients. A correlation between pregnancy outcome and postpartum course has been reported for essential thrombocythemia, but corresponding data for PV are lacking so far., Methods: In 41 PV pregnancies, the pregnancy outcome, the use of PV-specific therapies (ie, acetylsalicylic acid, low-molecular weight heparin and/or interferon-alpha), and the postpartum PV course were investigated., Results: A live birth rate of 51.2% (21/41 pregnancies) was observed. 43.9% of pregnancies ended in spontaneous abortion and 4.9% in stillbirth. A significantly increased live birth rate occurred in pregnancies with PV-specific therapies compared to standard antenatal care (69.0% vs. 8.3%; P < .0019). The use of PV-specific therapy significantly increased the number of maternal hemorrhages (P = .021) without increasing the risk of fetal complications. During the median postpartum follow-up period of 1.2 years (range 0.1-13.7), complicated postpartum PV occurred significantly more often after miscarriages (P = .035)., Conclusions: According to our analysis, PV-specific therapy improved the live birth rate. Significantly more complicated postpartum PV courses were observed after miscarriages., (© 2021 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Objectives: Assessment of "real-world" treatment strategies and outcome in Dutch polycythemia vera (PV) patients., Methods: Retrospective chart review in 150 patients with PV (WHO 2008 diagnostic criteria) from 10 major non-academic hospitals in the Netherlands., Results: Patients (median age 64 years, 49% male) frequently had cardiovascular risk factors (56%) and prior vascular events (31%). About 70% of patients were high-risk, based on ELN criteria. However, the majority of patients were treated with phlebotomies alone (55%). Cytoreduction with hydroxyurea (HU) was received by 44% as part of their initial therapy, with or without phlebotomies. The time to achieve the 45% hematocrit target was shortest in patients treated with phlebotomies with or without HU (125 ± 99 and 197 ± 249 days, respectively) compared to patients treated with only HU (232 ± 216 days). Leukocyte and platelet levels were lower in HU-treated patients, and ELN response targets were more often reached. During the median follow-up period of 4.1 years, 14 patients (9%) suffered a thrombotic vascular event., Conclusions: In Dutch clinical practice, there is major clinical variation in treatment strategies for PV. Phlebotomizing patients shorten the time to achieve hematocrit control, while HU better controls platelet and leukocyte levels. The thrombotic vascular event rate remains clinically significant., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The current survey aimed to gather predefined disease parameters and treatment strategies to characterize the polycythemia vera (PV) patient population in Belgium., Methods: Cross-sectional data from PV patients, seen at least once between May 2014 and May 2015 at 10 sites in Belgium, were collected in aggregated form and analyzed descriptively and quantitatively., Results: Data from 343 PV patients were collected. Of these, 174 (50.7%) were male and 256 (74.6%) were ≥60 years of age. Ninety-two (26.8%) had a prior history of thrombotic events. Considerable proportions of patients had increased hematological parameters (hematocrit > 45% [31.2%], leukocytes > 10 × 10 9 /L [33.3%], and platelet > 400 × 10 9 /L [38.2%]). Most patients had non-palpable spleen (284, 87.7%) and no phlebotomies during the past 6 months (197, 57.4%). Low-dose aspirin was given as thrombosis prophylaxis in 249 (72.6%) patients, while 232 (67.6%) received hydroxyurea (HU) as cytoreductive treatment. Forty-one patients (12.0%) were reported as resistant and/or intolerant to HU. Seventeen patients (5.0%) received ruxolitinib in the context of clinical trials., Conclusion: This survey provides better insight into the characteristics of Belgian PV patients and currently used treatment strategies. It shows that 232 (67.6%) PV patients continue to receive HU despite being potentially HU-resistant., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Severe thrombocytopenia (platelets <50 × 10 9 /L) is associated with very poor outcome of patients with myelofibrosis (MF). As patients with primary myelofibrosis (PMF) differ from patients with postessential thrombocythemia (PET-MF) and postpolycythemia vera myelofibrosis (PPV-MF), we aimed to evaluate the significance of low platelets among these patients. We present clinical characteristics and outcome of patients with either PMF, PPV-MF, or PET-MF, and thrombocytopenia who presented to our institution between 1984 and 2015. Of 1269 patients (877 PMF, 212 PPV-MF, 180 PET-MF), 11% and 14% had platelets either <50 × 10 9 /L or between 50-100 × 10 9 /L, respectively. Patients with platelets <50 × 10 9 /L were most anemic and transfusion dependent, had highest blast count and unfavorable karyotype. In general, their overall and leukemia-free survival was the shortest with median time of 15 and 13 months, respectively; with incidence of acute leukemia almost twice as high as in the remaining patients (6.9 vs 3.6 cases per 100 person-years). Nevertheless, this observation remains mostly significant for patients with PMF, as those with PEV/PVT-MF have already significantly inferior prognosis with platelets <100 × 10 9 /L., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Polycythemia vera (PV)-related symptoms may not be adequately controlled with conventional therapy. This current analysis of the RESPONSE trial evaluated the effects of ruxolitinib compared with standard therapy on quality of life (QoL) and symptoms in patients with PV who were hydroxyurea resistant/intolerant., Methods: In the previously reported primary analysis, ruxolitinib achieved the primary composite endpoint of hematocrit control and ≥35% reduction in spleen volume at Week 32. The current analysis evaluated patient-reported outcomes using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), and the Patient Global Impression of Change (PGIC)., Results: Compared with standard therapy, ruxolitinib was associated with greater improvements in global health status/QoL, functional subscales, and individual symptom scores of the EORTC QLQ-C30. At Week 32, more patients in the ruxolitinib arm (44%) achieved a ≥10-point improvement in global health status/QoL vs. standard therapy (9%). Improvements in MPN-SAF symptom scores were consistent with improvements in EORTC QLQ-C30, PSIS, and PGIC scores., Conclusions: Ruxolitinib provides clinically relevant improvements in QoL and ameliorates symptom burden in patients with PV who are hydroxyurea resistant/intolerant., (© 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.)

Treatment of essential thrombocythemia (ET) and polycythemia vera (PV) is aimed at preventing vascular complications, which are the main cause of morbidity and mortality in these diseases. Over the years, clinical trials have demonstrated that the incidence of thrombosis and bleeding can be reduced by controlling the blood cell counts, but the target hematological levels have varied across the studies. In this article, we review the evidence supporting the use of predefined target hematologic values for the management of ET and PV in routine clinical practice. At present, the recommended target hematocrit in PV is below 45%, regardless of the patients' risk profile. Concerning platelet counts, no direct correlation has been demonstrated with thrombotic risk in either ET or PV. Thus, although cytoreductive treatment reduces the rate of vascular complications in high-risk patients, no particular threshold of the platelet counts has been shown to be more protective against thrombosis. Extreme thrombocytosis is a risk factor for bleeding, particularly when aspirin or anagrelide are given. Leukocytosis at baseline or during follow-up appears to be a risk factor for thrombosis, mostly in high-risk patients. However, the clinical benefit of strictly controlling this parameter is not yet established. Finally, standardized definitions of response to cytoreductive treatment in ET and PV have recently been published. Nevertheless, they have been produced to compare the efficacy of new therapies in clinical trials, whereas its relevance in clinical practice has been questioned in retrospective studies showing that such response definitions do not correlate with the patients' clinical outcome., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The Budd-Chiari syndrome (BCS), characterized by the obstruction and occlusion of the suprahepatic veins, is a rare but typical complication occurring in patients with polycythemia vera (PV). We describe three young women who developed BCS as first manifestation of PV, in association with an inherited thrombophilic state and in the absence of concomitant use of oral contraceptives. Our report illustrates the existence of an aggressive form of myeloproliferative disorder, which requires prompt recognition and immediate therapeutic intervention including cytostatic drugs and anticoagulant treatment. Furthermore, we suggest the need of routine screening for thrombophilic state in young women affected by PV.

The prevailing attitudes regarding diagnostic and therapeutic procedures in patients with polycythaemia vera (PV) among Swedish haematologists were surveyed by way of a mailed questionnaire in August 2002. Among diagnostic procedures frequent use is reported for arterial O(2) saturation, spleen size determination, bone marrow histology, serum erythropoietin, serum cobalamins and leukocyte alkaline phosphatase score, while direct determination of the red blood cell mass is used infrequently (seldom or never by 82%). Among therapeutic modalities hydroxyurea and phlebotomy alone were most frequently used. The (32)P therapy was used at least sometimes by 57% of the physicians, and more widely in the university clinics. Anagrelide and alfa-interferon was used in a minority of patients only. The use of prophylactic acetylsalicylic acid was very variable. The majority of the physicians had an aim for their phlebotomy treatment at a level of 0.45 or less, but 21% used a level of 0.46-0.49 and 8% a level of 0.55-0.60 (in younger patients). The platelet level, at which myelosuppressive therapy was initiated, also varied, from 400 x 10(9)/L to >1500 x 10(9)/L. It can be concluded that in practical clinical work in Sweden the diagnosis of PV is established by frequent use of serum erythropoietin, bone marrow examination and spleen size determination. The use of different therapeutic modalities is very variable. Many physicians carry out their phlebotomy treatment with less intensity compared with national and international recommendations.

The use of radioactive phosphorus (32P) to treat the myeloproliferative disorders (chronic leukemia, polycythemia vera and essential thrombocythemia) began in 1939 when John H. Lawrence treated the first patient on the basis of work done in the laboratory animals that found localization of the radioisotope in the spleen, liver, bone and in leukemic cells sufficient to indicate a therapeutic potential. After World War II when 32P became widely available, it was used extensively to treat the chronic leukemias and polycythemia vera. Its use in the treatment of essential thrombocythemia began later in 1950. Today it is not widely used in the treatment of the chronic leukemia, if at all, its use in polycythemia vera appears to have decreased substantially and replaced by hydroxyurea, and its use in the management of essential thrombocythemia is not widespread. In each instance it has been replaced by a drug developed for use in cancer chemotherapy, and in some instances by interferon. It probably has wider use in polycythemia vera in the rest of Western Europe than in the UK, and there are cogent reasons to suggest that it may be the best tool for the treatment of polycythemia vera. Thus have we discarded a treatment modality that in polycythemia vera may be the best?

We report on long-term therapeutic efficacy and toxicity of recombinant interferon-alpha 2a (rIFN-alpha) in a series of 38 patients with polycythaemia vera (PV). In all patients haematocrit was first brought into the normal range by venesection; rIFN-alpha was then begun at a starting weekly dose of 9,000,000 IU. Complete response (CR) was defined as persistence of normal haematocrit without venesection and partial response (PR) as >50% reduction of phlebotomy requirement. Eleven patients (28.9%) achieved CR and 8 (21.0%) PR. Median duration of treatment for all responsive patients was 40 months; 12 patients are still responsive and under treatment after 13, 15, 25, 35, 40, 41, 43, 49, 50, 51, 52 and 52 months of therapy with rIFN-alpha. In responsive patients, rIFN-alpha also normalized leucocyte counts, platelet counts and spleen enlargement; rIFN-alpha also relieved generalized pruritus in all 10 patients displaying this symptom. Early toxicity (flu-like syndrome) was observed in 23.6% and late toxicity (severe weakness) in 13.1% of patients, requiring rIFN-alpha treatment suspension in all cases. Progression to leukaemia was observed in none of the 10 patients treated only with rIFN-alpha and in one of the 12 who received alkylating agents before enrolment in this study. According to these data, rIFN-alpha seems to be an effective and safe treatment option for PV.

By using an immunoradiometric method with a stated detection limit of < or =1 IU/l (stated normal reference limit in adults 3.7-16 IU/l) we determined EDTA-plasma erythropoietin (EPO) in 58 patients with polycythaemia vera (PV) and 49 patients with essential thrombocythaemia (ET). At the time of blood sampling, 20 of the PV patients were newly diagnosed and untreated, 23 were treated by phlebotomy only, and 30 also received myelosuppressive treatment (with 32P, hydroxyurea or alpha-interferon). Of the ET patients 24 were untreated and 28 received myelosuppressive therapy. For comparison plasma EPO was also determined in 10 patients with pseudopolycythaemia (PP). In this latter group the results for plasma EPO agreed well with the cited normal reference limits. The majority of untreated PV patients (12/20) had undetectable plasma EPO concentration, and the remainder all had values below the lower normal reference limit. Plasma EPO in PV was not significantly influenced by phlebotomy therapy. Twelve of the 24 untreated ET patients (50%) had plasma EPO values below the reference interval (undetectable in 2 patients). The mean EPO concentration was significantly lower in PV patients receiving phlebotomy therapy than in patients with untreated ET. In the total material of PV and ET treated with myelosuppressive agents the PV patients showed significantly lower values for EPO concentration than did patients with ET. The present results support the view that EPO measurements by high-detectability methods are diagnostically useful and should be included in the panel of new criteria for the diagnosis of PV.

Polycythemia vera (PV) is a chronic myeloproliferative disease. The use of recombinant alpha 2a Interferon (IFN) therapy in this disease is a novel approach. We applied Fourier-transform infrared microspectroscopy (FT-IR-M) to investigate the behavior and therapeutic responsiveness of PV patients treated with IFN. A spectroscopic parameter (A1/A2) was used, corresponding to the ratio of the integrated areas of the bands at 1080 cm-1 and at 1540 cm-1 due to nucleic acids and proteic components, respectively, calculated on the spectra of single megakaryocytes (MKs). In previous studies, we have pointed out that MKs in PV have a surprisingly strong myeloproliferative impulse when compared to MKs from other chronic myeloproliferative diseases. Nine patients out of the 11 studied exhibited a satisfactory responsiveness to the IFN treatment. Ten patients were evaluated by the A1/A2 parameter. In 8 of these, a good agreement was seen between this parameter and the laboratory data commonly used for the assessment of this disease. The infrared parameter, which we propose, proves to be an original, reliable method for the evaluation of recombinant alpha 2a IFN responsiveness in this disease.

Pro-collagen III (PC III) has been proposed as a useful value for diagnosis and follow-up of myeloproliferative disorders. A significant difference is observed between polycythaemia vera (PV) and essential thrombocythaemias (ET) on one hand, and the pure erythrocytoses (PE) on the other hand, but a large overlap makes this test of low diagnostic value. High values are observed in primary and post-PV myelofibrosis, but excessive PC III levels in active PV are not predictive of evolution toward myelofibrosis. PC III level is lower in myelo-suppressed patients (32P, or hydroxy-urea) than in active cases or in patients treated by phlebotomies. We conclude that PC III measurement is of low diagnostic value for discriminating PV and PE, does not appear to allow short-term prediction of evolution to myelofibrosis, but may be useful to evaluate the role of treatment in delaying progression of PV toward myelofibrosis.