Juvenile myelomonocytic leukemia in an infant with congenital human immunodeficiency virus and cytomegalovirus infection

Abstract

An 11-month-old boy was found to have bicytopenia and leukocytosis on routine attendance at a pediatric infectious diseases clinic. The child was under review for congenital co-infection with the human immunodeficiency virus (HIV) and cytomegalovirus (CMV). He was on antiretroviral therapy and had previously been treated with valganciclovir. His foster mother had no new concerns, and he had not had any fever recently. No significant abnormality was found on physical examination. His blood count showed a normocytic normochromic anemia (hemoglobin concentration 95 g/L), white cell count 26.5 × 109/L, and platelet count 47 × 109/L. There was monocytosis (7.7 × 109/L) and basophilia (0.3 × 109/L). In addition his blood film showed nucleated red blood cells, dysplastic basophils and eosinophils, granulocyte precursors, and occasional blast cells (images). High performance liquid chromatography showed hemoglobin F of 37%. Opinion was divided as to whether the abnormalities were secondary to CMV infection or malignancy. A diagnosis of juvenile myelomonocytic leukemia (JMML) was favored and further investigations were therefore performed. Abdominal ultrasound examination showed the spleen to measure 9.5 cm. A bone marrow aspirate showed active erythropoiesis with reduced granulopoiesis and megakaryocytes. Blast cells were 7% on cytology and 10% on flow cytometry; they expressed CD45 (moderate), CD33, CD117, CD7, and CD56. Monocytic markers were expressed by 32% of cells: CD45 (strong), CD4 (weak), CD64, CD11b, CD13, CD14, CD36, and CD56. Fluorescence in situ hybridization showed monosomy 7 in 64% of cells. Molecular analysis showed an NRAS Q61K mutation (PTPN11 and KRAS were wild type). Subsequently he was found to have a negative PCR for CMV, a low HIV viral load and a CD4-positive lymphocyte count of 2770 × 106/L. CMV infection in infants can cause a leukemoid reaction that resembles JMML.1 However an increased basophil count, dysplastic eosinophils and basophils, and an increased hemoglobin F would not be expected. Careful examination of the blood film suggested the correct diagnosis, which was confirmed by bone marrow examination and cytogenetic analysis. None.