Case Presentation
The patient is a 37-week gestation male delivered via cesarean section due to breech presentation. Birth weight was 2880g. Promptly upon delivery, the neonate exhibited respiratory compromise necessitating urgent endotracheal intubation and conventional mechanical ventilation.
He was noted to have distinct facial dysmorphology consistent with Trisomy 21. Initial complete blood count (CBC) showed a white blood cell (WBC) count of 25,100/mL with 21% blasts, hemoglobin of 16.7 g/dL, and a platelet count of 633,000/mL.
While the neonate’s oxygen saturation exhibited some improvement following mechanical ventilation, his PaO2 remained low. A chest X-ray showed no acute cardiopulmonary process. A discrepancy between pre- and post-ductal saturations prompted an echocardiogram which demonstrated elevated right ventricular pressures, with pulmonary pressures measuring at two-thirds the systemic level, and a patent ductus arteriosus (PDA) characterized by bidirectional flow.
In light of deteriorating respiratory function and severe pulmonary hypertension, the infant was switched to high-frequency jet ventilation (HFJV). Subsequently, the neonate was transferred to our tertiary care facility. Despite high-frequency jet ventilation, adjunctive inhaled nitric oxide therapy, and administration of corticosteroids at stress dosages, his oxygenation index and clinical condition continued to decline. This downward trajectory necessitated the initiation of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) on the third day of life, with successful decannulation on the sixth day. This infant required ECMO secondary to his pulmonary hypertension that was not thought to be a consequence of his TAM.
A CBC on the third day of life revealed a reduction in the white blood cell count to 16,000/mL with 45% blasts, hemoglobin of 11.4 g/dL, and a platelet count of 252,000/mL.
Peripheral blood specimen was sent to Hematologics and it was found to have 12% blasts and 1% micromegakaryocytes. Platelets were noted to be increased in number and in size. (Fig. 1). Flow cytometry confirmed blasts that expressed CD4 and CD36 but lacked CD64 and HLA-DR; an immunophenotype that is associated with myeloid proliferation in patients with Down syndrome. Sequencing of Exon 2 of GATA1 did not find any mutations. Hematologics does not sequence the entireGATA1 gene, so next generation sequencing (NGS) was performed by NEO genomics using their expanded myeloid panel called NeoTYPE ᵀᴹ Analysis, Myeloid Disorders Profile. No pathogenic mutations were detected in any of the genes on the NGS panel (Figure 2).
Between day 3 and day 15 of life, there was a progressive rise in platelet count, as shown in Table 1. Prophylactic administration of aspirin was started on day 14 due to a platelet count of greater than two million and the infant’s significant risk factor for thrombosis; his carotid end-to-end anastomosis after coming off of ECMO. On day 13, Cytarabine chemotherapy was initiated due to a platelet count of 2,595,000/mL. On the second day of Cytarabine therapy, the platelet count peaked at 2,764,000/mL. Patient completed the seven day course of low-dose Cytarabine therapy (1.5mg/kg/day) on day 19. The platelet count declined after completion of the Cytarabine course. Beyond the anticipated myelosuppression, the infant did not have any side effects from the chemotherapy. The infant has ongoing close follow up with Hematology/Oncology. He has been clinically well. The platelet count normalized and the WBC count remains normal.