Essential thrombocythaemia in children: is a treatment needed?

Randi, Maria Luigia; Putti, Maria Caterina

doi:10.1517/eoph.5.5.1009.31080

Cited by 4 publications

(6 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, new diagnostic and prognostic classifications might help in shaping improved therapeutic recommendations, with wide implications. 24 In conclusion, the heterogeneous molecular features found in our large set of pediatric ET cases may help in defining various subgroups, allowing for the clinical course to be predicted, mainly for thrombotic risks. This is necessary to assess which child with ET really deserves cytoreductive therapy, as already defined for adults.…”

Section: Resultsmentioning

confidence: 84%

Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative

Randi

Putti

Scapin

et al. 2006

Blood

Self Cite

View full text Add to dashboard Cite

Essential thrombocythemia (ET) is rare in children, and little or no information is available about clonality or JAK2 mutations. However, the analyses in this work prove useful for the diagnosis of adult myeloproliferative disorders (MPDs). We evaluated the clonality status and V617FJAK2 mutation in 20 children affected by ET and compared them with 47 consecutive adult ET cases. Clonality was evaluated on the DNA of granulocytes and on the RNA of platelets. V617FJAK2 was analyzed by sequencing tests, allelespecific polymerase chain reaction (PCR), and digestion by BsaXI. A monoclonal pattern was found in 4 (28.5%) of 14 children and in 45% of informative adults. Heterozygous V617FJAK2 was found less frequently in children than in adults (P < .009). Only 2 girls showed both the V617FJAK2 mutation and a monoclonal pattern; one of them was the only child presenting a major thrombotic complication. In contrast to adults, most children with ET do not show either a clonal disorder or the V617FJAK2 mutation. IntroductionThe diagnosis of essential thrombocythemia (ET) is usually made by exclusion criteria because no biologic markers are known to differentiate it either from primitive myeloproliferative disorders (MPDs) 1 or from reactive thrombocytosis. 2 The primitively proliferative nature of ET was first documented by Fialkow et al 3 who analyzed female patients for X-chromosome inactivation patterns (XCIPs) of G6PDH. It was found therein that 3 cases showed clonal expansion. However, further studies 4,5 demonstrated that only 20% to 35% of adult ET is monoclonal. Therefore, it is possible that monoclonal and polyclonal patterns define different disorders with a similar phenotype. It is relevant that recently a somatic mutation of Janus kinase 2 (JAK2) was found in about 35% to 50% of adult ET patients. 6,7 ET in pediatric age is a rare disorder that might also embed a spectrum of different diseases. 8 Unaware of previous comparative reports, we evaluated the clonal patterns and JAK2 gene mutations in pediatric ET patients. Study designWe studied 15 girls and 5 boys affected by ET in agreement with the Polycythemia Vera Study Group criteria 9 : ET diagnosed in pediatric age; platelet count continuously more than 800 ϫ 10 9 /L (range, 850-4500 ϫ 10 9 /L); and no known causes of reactive/secondary thrombocytosis. None of the children had any family history of either MPD or thrombocytosis. None had a prothrombotic condition. Moreover, in these patients, serum erythropoietin (EPO) and thrombopoietin (TPO) contents, platelet function, standard cytogenetic analysis, bcr/abl rearrangement, and sequences of TPO and c-MPL genes 10 were evaluated; no abnormality was found. The clinical findings and therapeutic options adopted are summarized in Table 1. Approval for these studies was obtained from the Padua University Department of Medical and Surgical Sciences institutional review board, and informed consent was provided according to the Declaration of Helsinki.For comparison as adult controls, 36 consecutive women and 11 men...

show abstract

Section: Resultsmentioning

confidence: 84%

Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative

Randi

Putti

Scapin

et al. 2006

Blood

Self Cite

View full text Add to dashboard Cite

show abstract

“…Children with ET seem to have a lower risk of thrombotic complications than adults, but they often suffer from headache. No guidelines are currently available for pediatric ET due to the limited body of information on the diagnosis and prognosis of these rare cases [41].…”

Section: Life Expectancy Prognostic Factors and Progression To Leukmentioning

confidence: 99%

Essential thrombocythemia: past and present

Fabris

Randi

2009

Intern Emerg Med

Self Cite

View full text Add to dashboard Cite

Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by sustained increase in platelet number and tendency for thromboembolism. A somatic point mutation that causes a constitutive activation of the JAK2 gene is found in one in two ET patients. ET is more common in women, its incidence being 0.6-2.5/100,000 patient/year and the median age at diagnosis is 65-70 years. ET can affect all age groups, including children (0.09 cases/year), and is often diagnosed in the third-fourth decade of life. Rare cases of familial ET have been reported. Miscarriages are 3-4 times more common among women with ET than in the general population, especially in patients carrying JAK2V617F. Microvascular disturbances are typical of ET, but a major thrombosis (2/3 arterial and 1/3 venous; 1, 2-3% patient/year) is the main cause of morbidity and mortality. Age over 60 years and/or previous thrombosis are validated risk factor for thrombosis. Hemorrhages occur in 0.33% patient/year, mainly in those with a platelet count over 1,500 x 10(9)/L. Progression to myelofibrosis and leukemia is more common in patients carrying the JAK2V617F mutation, and is estimated to occur in 0.16% and 0.12% patient/year, respectively. The ET-related mortality ratio with respect to the general population is 1:1, while for polycythemia vera it is 1.6:1. Low-dose aspirin is useful for microvascular disturbances, and in the primary and secondary prevention of major thrombosis in high-risk patients, but it is not recommended in patients with a platelet count over 1,500 x 10(9)/L. Hydroxyurea is used as first-line treatment in high-risk patients. Other drugs available are alpha-interferon, anagrelide, pipobroman and busulphan.

show abstract

“…A significant reduction in the incidence of thrombotic complications has been demonstrated in a clinical trial in patients with primary thrombocytosis of all ages (Cortelazzo et al , 1995). However, the risk of leukaemic transformation after long‐term treatment with hydroxyurea in children and young adults is still a major concern, and its use is controversially discussed (Cheung et al , 2004; Randi & Putti, 2004; Schafer, 2004). Two recent studies reported no increased incidence of leukaemic or neoplastic transformation after long‐term treatment with hydroxyurea in young adults (19–49 years) with primary thrombocytosis and in children with severe sickle cell disease (Falanga et al , 2000; Finazzi et al , 2003).…”

Section: Treatment Options In Non‐familial Primary Thrombocytosismentioning

confidence: 99%

“…Anagrelide is administered orally and has no known leukaemogenic potential. Therefore, some authors consider anagrelide as first‐line therapy for non‐familial primary thrombocytosis in children (Randi & Putti, 2004). A long‐term analysis of the use of anagrelide in young patients with primary thrombocytosis showed good tolerability, but complications were still high, with thrombosis in 20%, major bleeding in 20% and anaemia in 24% of patients.…”

Section: Treatment Options In Non‐familial Primary Thrombocytosismentioning

confidence: 99%

Primary and secondary thrombocytosis in childhood

2005

View full text Add to dashboard Cite

Summary This review summarizes current data on the pathomechanisms and clinical aspects of primary and secondary thrombocytosis in childhood. Primary thrombocytosis is extremely rare in childhood, mostly diagnosed at the beginning of the second decade of life. As in adults, the criteria of the Polycythemia Vera Group are appropriate to diagnose primary thrombocytosis. The pathomechansims of non‐familial forms are complex and include spontaneous formation of megakaryopoietic progenitors and increased sensitivity to thrombopoietin (Tpo). Familial forms can be caused by mutations in Tpo or Tpo receptor (c‐mpl) genes. These mutations result in overexpression of Tpo, sustained intracellular signalling or disturbed regulation of circulating Tpo. Treatment of primary thrombocytosis is not recommended if platelet counts are <1500/nl and bleeding or thrombosis did not occur in patient's history. In severe cases, decision on treatment should weigh potential risks of treatment options (hydroxyurea, anagrelide) against expected benefits for preventing thrombosis or haemorrhage. Secondary thrombocytosis is frequent in children, in particular in the first decade of life. Hepatic Tpo production is stimulated in acute response reaction to a variety of disorders. Thrombosis prophylaxis is not required, even at platelet counts >1000/nl, except for cases with additional prothrombotic risk factors.

show abstract

Essential thrombocythaemia in children: is a treatment needed?

Cited by 4 publications

References 24 publications

Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative

Pediatric patients with essential thrombocythemia are mostly polyclonal and V617FJAK2 negative

Essential thrombocythemia: past and present

Primary and secondary thrombocytosis in childhood

Contact Info

Product

Resources

About