PC1186: Acute Myelogenous Leukemia in an Extremely Premature Trisomy 21 Neonate Presented in Utero

Introduction: Infants with Trisomy 21 (T21) are at risk for developing transient myeloproliferative disorder (TMD) during the newborn period, and acute myelogenous leukemia (AML) during early childhood. TMD occurs in about 10% of infants with T21 and is associated with subsequent development of AML in 20% of affected infants. Perinatal AML is extremely rare. Herein we present a premature T21 infant born with AML.

Case Description: Our patient was an 830-gram female product of a dichorionic diamniotic twin gestation. Prenatal imaging revealed thicken nuchal cord, polyhydramnios, and possible atrioventricular canal defect on one twin while the other had ascites. Noninvasive prenatal screening showed high risk of Trisomy 21. They were delivered at 26 weeks gestation for worsening ascites and absent diastolic placental flow in the affected twin. Following delivery, she had respiratory failure, severe coagulopathy, hepatosplenomegaly, ascites, anuria, hypotension, and a grade 3 intraventricular hemorrhage (IVH). Labs revealed leukocytosis of 157.3 x 109/L with 91% blast cells, critical liver dysfunction and coagulopathy (figure 1). Peripheral blood flow cytometry revealed AML/blast crisis. Parents were informed of the grave conditions and limited options. They wished to have a trial of chemotherapy. Cytarabine (3.83 mg/kg/dose IV every 12 hours) was started on day of life 2. Tumor lysis syndrome was treated with Rasburicase. Allopurinol was not given due to nil per os status. Her labs improved after 2 days of Cytarabine (WBC 16.5 x 109/L), but she continued to have refractory severe anuria, coagulopathy, hypotension, and worsening IVH. Life support was withdrawn on day of life 5.

Discussion: Children with T21 have increased risk of developing leukemia. Myelogenous leukemia in Down syndrome (ML-DS) generally develops before the age of 5. Most often, ML-DS is preceded by the preleukaemic syndrome TMD but ML-DS presentation at birth, as in our patient, is very rare. The initial event in T21-associated preleukaemic and leukemic conditions is thought to be the perturbation of fetal hematopoiesis due to trisomy 21, itself. Abnormal hematopoiesis can happen as early as during the first trimester.
Neonatal AML is typically initially treated with cytarabine and anthracyclines. Hematopoietic stem cell transplantation is also an option. Besides cell counts, clinical condition of the patient plays important role in the decision-making for supportive care of the neonate. Mortality is very high despite good response to chemotherapy due to serious complications coupled with extreme prematurity as in the presented case.

Conclusion: Children with T21 have a unique predisposition to abnormal myelopoiesis, including both TMD and AML. AML, even when presenting neonatally, responds to cytarabine, but patients often succumb to multiorgan failure. An honest discussion regarding the risks and benefits of AML treatment considering an infant’s overall medical condition and the parents’ desires is essential.