Myeloproliferative neoplasms (MPNs) typically develop in patients over the age of 60. Sometimes, though, they arise in younger patients—much younger patients. What do these blood disorders look like in patients younger than 20?
An international team of researchers conducted a systematic review of all cases published in PubMed since 2005 that focused on essential thrombocythemia (ET) or polycythemia vera (PV) diagnosed in patients under age 20. They discovered 396 cases of ET and 75 cases of PV, after excluding any identified cases of familial MPN, which they described in a recent issue of Haematologica.
Young patient. Source: Getty
The incidence of MPNs in children and teens varied notably between countries, from 0.1 to 2.25 per 100,000 patients per year. The incidence per 100,000 patients per year of ET is about 0.6 compared to 0.18 for PV and 0.53 for primary myelofibrosis (PMF).
The young patients with ET were very young, with an average age of 9.3 years, of whom 57.6% were female. The patients with PV had a mean age of 12 years, with 45% being female.
Half of the patients had no symptoms at diagnosis. About 30% in both groups presented with headaches, 5.5% of ET patients had abdominal or bone pain as did 3.4% of patients diagnosed with PV. Thrombotic or hemorrhagic events led to diagnosis of 13.6% of PV patients and 4.7% of those with ET.
During follow-up, 9.3% of those with PV developed thrombosis compared to just 3.8% of those with ET. Venous events accounted for 84.2% of events, with thromboses of the splanchnic territories representing 75% of those and Budd-Chiari syndrome 62.5%, a notable divergence from patterns seen in older patients.
At diagnosis, 54.7% of ET patients had splenomegaly, as did 15.3% of PV patients, though there was not a high correlation between enlarged spleen and reported abdominal pain.
ET patients had a median leukocyte count of 10.6 x109/l, hemoglobin was 131 g/l and platelets were 1192 109/l. PV patients had a median leukocyte count of 13.2 109/l, hemoglobin was 180 g/, maximum hematocrit at 72.5% and platelets were 799 109/l.
Over a median follow up of 50 months,2% of patients evolved to secondary myelofibrosis. None progressed to acute leukemia. Three patients died, two of Budd-Chiari syndrome and one from pneumonia following a stroke.
Notably, 73% of the young patients with PV had “triple negativity,” that is, they lacked all three of the common mutations in the JAK2, CALR or MPL genes that drive most MPNs. The JAK2 exon 14 V617F mutation occurs in nearly all PV cases, making its absence in this group quite notable.
The researchers identified a similar genetic anomaly in the ET patients, 57% of whom were triple negative. As with PV, triple negativity in ET is very unusual; 85% to 90% of all ET patients express at least one of three common mutations.
The absence of the big three mutations in these young patients and a relatively low rate of reported bone biopsies challenges guidelines written for much older patient groups, which consider driver mutations and bone marrow biopsy central to diagnosis. On the one hand, the differences seen here could indicate that some of the patients may have been misdiagnosed. Alternatively, they could illuminate different mechanisms in proliferation specific to younger patients.