Characteristics and outcomes of patients with essential thrombocythemia or polycythemia vera diagnosed before 20 years of age: a systematic review

Abstract

Although it is well known that myeloproliferative neoplasms occur in younger patients, few large cohorts of such patients have been reported. Thus, our knowledge about circumstances of diagnosis, outcome and treatment is limited, especially for children and young adults. We therefore performed a systematic review of cases, published since 2005, concerning patients aged below 20 years at the time of diagnosis of essential thrombocythemia or polycythemia vera. We identified 396 cases of essential thrombocythemia and 75 of polycythemia vera. The median age at diagnosis was 9.3 and 12 years, respectively, and females constituted 57.6% and 45% of the groups, respectively. Half of the patients were asymptomatic at diagnosis. The proportion of so-called triple negativity was high: 57% in essential thrombocythemia and 73% in polycythemia vera. The incidence of thrombosis during the follow-up was 9.3% in patients with polycythemia vera and less, 3.8%, in those with essential thrombocythemia. Venous events were predominant (84.2%), with hemorrhagic episodes being rarer (<5%). The risk of evolution also seemed low (2% to myelofibrosis and no reports of acute leukemia), but the median follow-up was only 50 months. Survival curves were not available. Half of the patients received an antithrombotic drug and 40.5% received a cytoreductive drug. All data should be analyzed with care because of the proportion of missing data (10.7% to 74.7%). This review highlights interesting points concerning this population of young patients with myeloproliferative neoplasms, including that such patients were identified as negative for all common driver mutations, but also shows the need for larger contemporary cohorts with longer follow-up to assess the true prognosis of these patients.

Complex intracranial vascular complications caused by essential thrombocythemia: a critical case report

“…The majority of patients with ET have JAK2V617F, CALR or MPL mutations (60, 20 and 3% respectively), and 10 ~ 20% of ET patients are triple-negative [ 1 ]. The most frequent symptoms include headache (27.5%) and abdominal or bone pain (5.5%), but half of ET patients are asymptomatic [ 9 ], and 14% of patients are diagnosed after arterial thrombosis [ 1 ]. The diagnosis of ET is established from platelet counts, bone marrow biopsy, and genetic testing, which can differentiate ET from other disorders, such as reactive thrombocytosis, chronic myelocytic leukaemia, polycythemia vera, primary myelofibrosis, myelodysplastic syndromes, or other myeloid neoplasms.…”

Clinical features of children with polycythemia vera, essential thrombocythemia, and primary myelofibrosis in Japan: A retrospective nationwide survey

“…We identified two children who developed subsequent leukemia, which has not been reported previously, and one of them died. Although hematologic findings are similar between cases of adult and pediatric MPNs in terms of clinical findings and genetic events, considerable differences have been indicated by several studies [3][4][5][6].…”

Emerging translational science discoveries, clonal approaches, and treatment trends in chronic myeloproliferative neoplasms

“…92 Recent efforts, however, suggest that with increasing awareness, the precise incidence is higher. 93,94 Such efforts have also identified several biological and clinical unmet needs. 95,96 For example, there is considerable ambiguity with regards to the causes of MPNs in children and adolescents.…”

“…Although the primary drivers of adult MPNs are well established, the molecular pathogeneisis in children is largely unkown, and some studies suggest higher rates of "triple-negative" disease ( Figure 6). 94,[97][98][99] This underscores the importance of identifying appropriate diagnostic criteria for use in pediatrics-while the WHO criteria may be appropriate for adults, they likely cannot be applied to children, who are more frequently triple negative and have different normal values than adults for certain blood counts, including red blood cell (RBC) count, Hb, and hematocrit (Hct), which vary with age. 100 Eight children with a JAK2 V617F -mutated MPN were examined to see if their type of MPN could be clearly discerned.…”

“…The BCR‐ABL1 ‐negative classical MPNs appear to be extremely rare in children, with PV and ET estimated to occur in one to two cases per 10 000 000 children annually . Recent efforts, however, suggest that with increasing awareness, the precise incidence is higher . Such efforts have also identified several biological and clinical unmet needs .…”