A 5 year old boy presents with malaise, pallor and fever. On clinical examination he has hepatosplenomegaly and lymphadenopathy. He also has neurofibromatosis. A full blood count is performed and the following results noted:
Hb 99 g/L, WBC 27.4 x 109/L and platelet count 206 x 109/L
The differential white cell count shows a left shift and a monocytosis of 11.5 x 109/L. A bone marrow aspiration is performed revealing an increase in myelopoiesis as well as a monocytosis. Cytogenetic studies demonstrate a monosomy 7. The HbF is raised at 6.4% (normal range for age is <1%). A diagnosis of juvenile myelomonocytic leukaemia (JMML) is made.
JMML was classified as a myelodysplastic syndrome (MDS) by the FAB classification. The World Health Organization (WHO) removed JMML from the MDS classification and placed it in a new category, namely Myelodysplastic/Myeloproliferative Diseases (MDS/MPD).
JMML typically presents in children less than 4 years of age, with most cases occurring under the age of 2 years. The disease is more common in males than females (male to female ratio approximately 2.5:1).
JMML is a clonal disease characterized by an elevated WBC that is usually less than 100 x 109/L with a left shift in the myeloid line. There is a peripheral monocytosis of more than 1 x 109/L with less than 20% blasts in the peripheral blood and bone marrow.
The HbF is raised for the age of the child.
The bone marrow is hypercellular with myeloid hyperplasia and decreased numbers of megakaryocytes. JMML lacks the Philadelphia chromosome or BCR / ABL fusion gene. Although cytogenetic abnormalities, including monosomy 7, occur in 30% to 40% of cases, no specific cytogenetic abnormality characterises JMML.
JMML is associated with the autosomal dominant neurogenetic disorder neurofibromatosis. Children with neurofibromatosis type 1 (NF1) are at increased risk for developing JMML.
Most cases of JMML have a mean survival between 1 and 2 years. Death is usually due to infection or progression of the disease.
Approximately 10% to 20% of cases evolve to acute leukaemia. Long term remission can only be achieved with bone marrow transplantation.