The revised WHO diagnostic criteria for Ph-negative myeloproliferative diseases are not appropriate for the diagnostic screening of childhood polycythemia vera and essential thrombocythemia

Teofili, Luciana; Giona, Fiorina; Martini, Maurizio; Cenci, Tonia; Guidi, Francesco; Torti, Lorenza; Palumbo, Giovanna; Amendola, Angela; Leone, Giuseppe; Foà, Robin; Larocca, Luigi Maria

doi:10.1182/blood-2007-06-094276

Cited by 47 publications

(53 citation statements)

References 23 publications

(41 reference statements)

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“…Of note is that the WHO diagnostic recommendations in children suspected with ET are thought to be not adequate and a specific set of diagnostic criteria is required. 5,6 Contrary to adults, most of children with ET present polyclonal, rather than monoclonal hematopoiesis, the capacity to form spontaneous colonies is present less often and the presence of JAK2 mutation is significantly less frequent than in the general MPN population. Therefore, the WHO criteria cannot be used for the diagnostic screening of these young patients.…”

Section: How To Diagnose Mpn In Children and Young Adultsmentioning

confidence: 99%

“…Owing to the rarity of MPN in children o18 years, very few studies with limited number of patients are available. 5,24 An extensive review of the literature describing the clinical course and treatment modalities of 35 PV cases in children was recently reported. 25 The youngest was 7 months and the oldest 17.5 years old (median age 11 years).…”

Section: How To Manage Childrenmentioning

confidence: 99%

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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%

Section: How To Manage Childrenmentioning

confidence: 99%

How to manage children and young adults with myeloproliferative neoplasms

Barbui

2012

Leukemia

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“…Given the lower frequency of JAK2 and MPL mutations in children, this set of diagnostic criteria probably needs to be modified for childhood ET and this concept has been supported by other groups. 87 Similarly, absence of a causative mutation in a child with a positive family history does not preclude the diagnosis of a hereditary thrombocytosis. …”

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confidence: 99%

Primary thrombocytosis in children

et al. 2014

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Myeloproliferative neoplasms are uncommon disorders in children, for which we have limited understanding of the pathogenesis and optimal management. JAK2 and MPL mutations, while common drivers of myeloproliferative neoplasms in adult patients, are not clearly linked to pediatric disease. Management and clinical outcomes in adults have been well delineated with defined recommendations for risk stratification and treatment. This is not the case for pediatric patients, for whom there is neither a standard approach to workup nor any consensus regarding management. This review will discuss thrombocytosis in children, including causes of thrombocytosis in children, the limited knowledge we have regarding pediatric primary thrombocytosis, and our thoughts on potential risk stratification and management, and future questions to be answered by laboratory research and collaborative clinical study. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o ngenerally on control at the transcriptional level. 13 This rate depends upon TPO binding to its receptor, which in turn depends upon how many TPO-R bearing cells are accessible, as well as how many receptors they express.14 Low platelet counts will lead to decreased TPO clearance (less receptors in the circulation) and therefore increased levels of TPO; the reverse occurs with higher platelet counts, i.e. thrombocytosis. There are variations to this basic principal, for example in the setting of idiopathic thrombocytopenia (thrombocytopenia due to destruction). In these cases, the number of megakaryocytes and megakaryocyte mass may also influence TPO regulation and circulating levels. 15,16 Causes of reactive thrombocytosis in childrenSecondary, or reactive, thrombocytosis is a common occurrence in children. It has been reported to occur in 6-15% of hospitalized children, with variations based on age. Most of these children had thrombocytosis that could be characterized as mild, but others transiently reached levels over 900,000. [17][18][19][20] Causes of secondary thrombocytosis are many and varied (Table 1). Infection is the most common, including viral and bacterial pathogens, and both acute and chronic infections. Especially in children under one year of age, any infection seems capable of triggering a high platelet count. Inflammatory diseases, e.g. Kawasaki disease, rheumatoid arthritis, and inflammatory bowel disease, are commonly associated with reactive thrombocytosis, as are hypoxia, trauma, blood loss, and malignancy. 19,21,22 Iron deficiency also seems to be a frequent cause of secondary thrombocytosis. 20 It is believed that underlying mechanisms of secondary thrombocytosis can be explained by upregulation of TPO expression and resultant increased TPO levels. Hepatic TPO mRNA expression is increased with inflammation. Figure 1 shows our groups' proposed diagnostic algorithm for approaching patients with elevated platelets. Evaluation for secondary causes, such as iron deficiency or inflammatory or infectious disorders is conducted. Iron deficiency and othe...

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“…In contrast, pediatric cases often recognize different pathogenetic mechanisms. We have recently demonstrated that the proposed diagnostic guidelines of MPDs based on the detection of JAK2 mutations 38 are not appropriate for pediatric patients 39 . Indeed, in the case of childhood MPDs, it should first be established if the disease is congenital or acquired.…”

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confidence: 99%