The Efficacy of Low-Dose Cytosine Arabinoside Therapy for Patients of Down Syndrome with Transient Abnormal Myelopoiesis

<Introduction> Transient abnormal myelopoiesis (TAM) occurs in about 10% of neonates with Down syndrome. While TAM is generally considered as self-limiting disease, substantial number of patients suffer from serious complications including liver fibrosis or pericardial effusion and eventually leads to fatal clinical outcomes. Low-dose cytosine arabinoside (CA) therapy has been reported to be effective for clinical symptoms of TAM patients, but it is still controversial as to which patient should be treated. We have retrospectively reviewed the clinical outcomes of TAM patients in our institution to confirm the efficacy as well as the safety of low-dose CA therapy by comparing the clinical outcomes before and after introduction of CA. <Patients> Before introduction of CA, we have experienced 20 TAM patients of 13 male and 7 female between September 1992 and November 2008. The median gestational age of those was 37w4d (range, 31w5d - 39w2d) , median peak value of white blood cell (WBC) count was 48×109/L (range, 19.8 - 399×109/L), and median peak direct bilirubin(DB) level was 0.9 mg/dL (range, 0.1 - 18.4 mg/dL), respectively. Sixteen of twenty patients (80%) had various complications including dyspnea, hepatosplenomegaly, pericardial effusion, and ascites. Since 2009, we have introduced low dose CA (0.4 - 1.0mg/kg/day) for those with high WBC count (>100×109/L) until WBC count decrease to 10×109/L . Three patients received chemotherapy, but one patient with high WBC count did not, because consent was not obtained. The median gestational age of those was 36w4d (range, 33w6d - 39w2d) , median peak value of WBC count was 106×109/L (range, 101 - 267×109/L), and median peak DB level was 1.95mg/dL (range, 1.0 - 11.0 mg/dL), respectively. All of them had various complications including dyspnea, hepatosplenomegaly, pericardial effusion, liver fibrosis and ascites. <Results> Before introduction of low dose CA therapy, five of six patients (83%) with high WBC count (>100×109/L) died of liver failure(4 of 5 patients) or AML, and one of 14 patients (7%) with low WBC count (<100×109/L) died of pneumonia at the age of eight without any relation to TAM. After introduction of CA, all three patients who received chemotherapy are alive without serious complications related to TAM or chemotherapy. Their blast cells in the peripheral blood disappeared promptly and liver dysfunction as well as biomarker of liver fibrosis is getting normalized. One patient who did not receive chemotherapy died of liver failure in spite of supportive care. <Conclusion> It is suggested that low dose CA therapy is safely conducted and is effective to improve the clinical outcomes of TAM patients with high WBC count. Prospective analysis is mandatory to confirm our findings by multi-institutional basis. Disclosures No relevant conflicts of interest to declare.