Clinical and Molecular Findings in Childhood Polycythemia Vera.

Background: Polycythemia vera (PV) and congenital erythrocytoses constitute extremely rare diseases in pediatric and juvenile patients. Systematic data on clinical and laboratory evaluations as well as on treatment modalities are sparse.

Aims/Methods: We developed a protocol (PV-ERY-KA 03) for the systematic collection of clinical, hematological, biological as well as treatment data of children and adolescents with PV or congenital erythrocytoses. The collaborative trial was initiated in March 2004.

Results: To date, 5 (2 male / 3 female) pediatric patients with PV have been enrolled. The median age at onset was 14 years (7–18.5 years). 4/5 patients are of German, 1/5 of Turkish origin. Only 3 patients presented with PV-related symptoms (Budd-Chiari syndrome, isolated headache, or headache together with tinnitus, dizziness and weakness). At first presentation, the median hemoglobin content was 18 g/dl (15.5–21.1 g/dl), the median hematocrit 0.60 (0.59–0.73). Thrombocytosis was present in 4/5, leukocytosis in 2/5 patients. All patients presented with mild to marked splenomegaly. Granulocytic PRV-1-mRNA expression and JAK2V617F mutation were assessed in 4/5 patients. PRV-1-mRNA expression was significantly elevated in 3 of them and borderline the 4th patient. 3 patients including the patient with borderline PRV-1-mRNA expression presented with a heterozygous JAK2V617F mutation. Treatment strategies included phlebotomy (4/5), hydroxyurea (1/5), IFN-alpha (1/5), and aspirin (3/5). Stem cell transplantation from a matched unrelated donor was performed in one patient (now in complete remission). Because of progressive liver failure, the patient with Budd-Chiari syndrome underwent orthotopic liver transplantation.

Conclusions: The activating JAK2V617F mutation previously reported to be present in up to 90 percent of adult PV patients, is also involved in childhood PV. The age of onset and clinical presentations in the rare cases of childhood PV are varied. Different treatment strategies are applied. A collaborative assessment of children with PV may help to optimise treatment in these patients, but may in addition contribute to a better general understanding of the disease’s pathogenesis.