Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel

Tefferi, Ayalew; Thiele, Jüergen; Orazi, Attilio; Kvasnicka, Hans Michael; Barbui, Tiziano; Hanson, Curtis A.; Barosi, Giovanni; Verstovšek, Srđan; Birgegård, Gunnar; Mesa, Ruben A.; Reilly, John T.; Gisslinger, Heinz; Vannucchi, Alessandro M.; Cervantes, Francisco; Finazzi, Guido; Hoffman, Ronald; Gilliland, D. Gary; Bloomfield, Clara D.; Vardiman, James W.

doi:10.1182/blood-2007-04-083501

Cited by 789 publications

(705 citation statements)

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“…3,4 These criteria combine genetic, clinical and pathological characteristics and emphasize the neoplastic nature of the previously termed myeloproliferative diseases and renamed them MPNs.…”

Section: How To Diagnose Mpn In Children and Young Adultsmentioning

confidence: 99%

How to manage children and young adults with myeloproliferative neoplasms

Barbui

2012

Leukemia

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On the basis of my personal clinical and research experience and validated by the current literature, my approach to the management of pediatric (age o18 years) and young patients (age o40 years) with classic myeloproliferative neoplasms is presented by focusing on diagnosis, patient communication, risk stratification and therapy. The WHO-2008 diagnostic criteria are recommended, even though in children suspected with essential thrombocythemia (ET), a specific set of diagnostic features may be required. Patient communication includes information on natural history, genetic abnormalities and counseling in all women of child-bearing age. The main challenge in children and young adults with ET and polycythemia vera (PV) is to avoid recurrence of major thrombosis by selecting those patients who ultimately can benefit from cytotoxic and antithrombotic therapy without increasing the incidence of drug-induced side effects. In asymptomatic low-risk patients no therapy is prescribed while in high-risk low-dose aspirin, hydroxyurea and interferon-alpha are my first line drugs. My first decision when considering treatment of a young patient with primary myelofibrosis (PMF) or post-PV or post ET-myelofibrosis, is whether he/she qualifies for bone marrow allotransplantation. In the remaining young PMF patients palliative therapy or experimental drugs are considered.Leukemia ( Keywords: myeloproliferative neoplasms; treatment; young people INTRODUCTION Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are currently classified among the bcr/abl-negative, 'classic' myeloproliferative neoplasms (MPNs) and represent a stem cell-derived clonal myeloproliferation. Hematopoietic progenitors derived from patients with MPNs are hypersensitive to the stimulation of physiological growth factors such as thrombopoietin or erythropoietin (EPO). 1 Since 2005, the pathophysiology of these diseases has advanced considerably with the discovery of an acquired mutation of JAK2 V617F in a vast majority of PV patients and in almost half of those with ET and PMF. 2 The mutation, located within the negative regulatory pseudokinase, or Janus homology 2 domain, causes cytokine-independent activation of several biochemical pathways implicated in EPO receptor signaling. Subsequently, mutations in MPL were reported in B4% of patients with ET or PMF. The significance of JAK2 and MPL mutations for the evolution of the MPNs and their relative roles in determining disease phenotype as well as progression to myelofibrosis and leukemic transformation are unclear at present.In this context, it should be underscored that most of the information in terms of diagnosis, prognosis and therapy focuses on the 'average' MPN patients of whom median age ranges between 60 and 65 years. On the other hand, less consistent data are available in the groups of MPN patients who are presenting below this median age such as pediatric and young adults (20% of MPN patients). This issue is now becoming more and more important, because with the ad...

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Section: How To Diagnose Mpn In Children and Young Adultsmentioning

confidence: 99%

How to manage children and young adults with myeloproliferative neoplasms

Barbui

2012

Leukemia

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“…[16][17][18][19] None of these mutations are MF-specific, and it is currently believed that these mutations constitute secondary events with poorly defined pathogenetic contribution. 16 Primary myelofibrosis is currently diagnosed according to WHO criteria, 20 whereas the International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria are used to diagnose post-PV or post-ET MF. 2 Patients typically present with anemia, marked splenomegaly, and characteristic laboratory features, including peripheral blood leukoerythroblastosis, dacryocytosis, increased serum lactate dehydrogenase level, excess circulating blasts, and bone marrow stromal changes (eg, collagen fibrosis, osteosclerosis, and angiogenesis).…”

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One Thousand Patients With Primary Myelofibrosis: The Mayo Clinic Experience

Tefferi

Lasho

Jimma

et al. 2012

Mayo Clinic Proceedings

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Objective: To share our decades of experience with primary myelofibrosis and underscore the importance of outcomes research studies in designing clinical trials and interpreting their results. Patients and Methods: One thousand consecutive patients with primary myelofibrosis seen at Mayo Clinic between November 4, 1977, and September 1, 2011, were considered. The International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS), and DIPSS-plus were applied for risk stratification. Separate analyses were included for patients seen at time of referral (Nϭ1000), at initial diagnosis (Nϭ340), and within or after 1 year of diagnosis (Nϭ660). Results: To date, 592 deaths and 68 leukemic transformations have been documented. Parameters at initial diagnosis vs time of referral included median age (66 vs 65 years), male sex (61% vs 62%), red cell transfusion need (24% vs 38%), hemoglobin level less than 10 g/dL (38% vs 54%), platelet count less than 100 ϫ 10 9 /L (18% vs 26%), leukocyte count more than 25 ϫ 10 9 /L (13% vs 16%), marked splenomegaly (21% vs 31%), constitutional symptoms (29% vs 34%), and abnormal karyotype (31% vs 41%). Mutational frequencies were 61% for JAK2V617F, 8% for MPLW515, and 4% for IDH1/2. DIPSS-plus risk distributions at time of referral were 10% low, 15% intermediate-1, 37% intermediate-2, and 37% high. The corresponding median survivals were 17.5, 7.8, 3.6, and 1.8 years vs 20.0, 14.3, 5.3, and 1.7 years for patients younger than 60 years of age. Compared with both DIPSS and IPSS, DIPSS-plus showed better discrimination among risk groups. Five-year leukemic transformation rates were 6% and 21% in low-and high-risk patients, respectively. Conclusion: The current document should serve as a valuable resource for patients and physicians and provides context for the design and interpretation of clinical trials.

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“…Laboratory tests which are significantly different in early PMF as compared with histologically confirmed ET (WHO-ET) include decreased Hb, increased white blood cell (WBC) and lactate dehydrogenase (LDH) values. Although bone marrow biopsy represents the gold standard for differentiating WHO-ET from early PMF [8], in clinical practice it might be very useful to know whether one or more of these baseline laboratory parameters may help to differentiate these two entities. To tackle this issue, we evaluated sensitivity (SE) and specificity (SP) of blood cells counts and LDH for the diagnosis of early PMF versus WHO-ET in an exploratory cohort of 536 histologically diagnosed patients aimed to propose an algorithm for the practical clinical use of these tests.…”

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Blood tests may predict early primary myelofibrosis in patients presenting with essential thrombocythemia

et al. 2012

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According to World Health Organization (WHO)-defined criteria, patients presenting clinically as essential thrombocythemia (ET) may show early primary myelofibrosis (PMF) with accompanying thrombocythemia [1]. Previous clinicopathological studies revealed that laboratory parameters like gender-matched hemoglobin (Hb), white blood cell (WBC) count, and particularly lactate dehydrogenase (LDH) values are significantly different in PMF [2]. By strictly applying the WHO criteria, our investigation was aimed to study sensitivity and specificity of these features in an exploratory cohort of 536 patients and to validate the results on an independently recruited series of 321 strictly corresponding patients. The discriminatory power of these parameters (Hb, WBC, and LDH) was tested by plotting their receiver operating characteristic curves. The best performance was found for LDH (areas under the curve, AUC 5 0.7059). WBC and Hb had superimposable curves, with AUC of 0.6279 and 0.6257, respectively. A diagnostic algorithm was generated by applying these parameters in a stepwise fashion. Nearly half of the patients could be correctly allocated to WHOdefined ET or early PMF in both cohorts investigated. It is important to note that this result does not substitute bone marrow morphology with hematological parameters, however, in clinical practice may alert physicians to get more suspicious of early PMF in a patient presumably presenting with ET.Following current criteria established by the World Health Organization (WHO), patients presenting with a clinical picture of essential thrombocythemia (ET) can actually have an early primary myelofibrosis (PMF) [3]. Incidences may vary depending on the accuracy of applied diagnostic guidelines [4][5][6] and was recently reported in about 18% of cases of socalled ET [7]. Laboratory tests which are significantly different in early PMF as compared with histologically confirmed ET (WHO-ET) include decreased Hb, increased white blood cell (WBC) and lactate dehydrogenase (LDH) values. Although bone marrow biopsy represents the gold standard for differentiating WHO-ET from early PMF [8], in clinical practice it might be very useful to know whether one or more of these baseline laboratory parameters may help to differentiate these two entities. To tackle this issue, we evaluated sensitivity (SE) and specificity (SP) of blood cells counts and LDH for the diagnosis of early PMF versus WHO-ET in an exploratory cohort of 536 histologically diagnosed patients aimed to propose an algorithm for the practical clinical use of these tests. This algorithm was then applied to an independently recruited validation cohort of 321 patients presenting with similar diagnosis of early PMF versus WHO-ET. The starting point of this study was an international database of 1,071 patients with ET either confirmed by WHO criteria (891 cases) or revised to early PMF (180 cases) as detailed elsewhere [7]. From this database, 536 patients (50%) who had complete laboratory data measured at diagnosis were extracted and c...

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Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel

Cited by 789 publications

References 43 publications

How to manage children and young adults with myeloproliferative neoplasms

How to manage children and young adults with myeloproliferative neoplasms

One Thousand Patients With Primary Myelofibrosis: The Mayo Clinic Experience

Blood tests may predict early primary myelofibrosis in patients presenting with essential thrombocythemia

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