Exchange transfusion and systemic corticosteroid therapy for transient abnormal myelopoiesis in patients with Down syndrome: a report from the JCCG TAM-10 trial.

Transient abnormal myelopoiesis (TAM) in Down syndrome is a unique hematologic disorder that resolves spontaneously; however, approximately 10%-20% of patients experience early mortality due to severe complications. While low-dose cytarabine (LDAC) has been shown to reduce early mortality in life-threatening TAM, the clinical utility of noncytotoxic interventions, such as exchange transfusion (ExT) and systemic corticosteroids (CS), remains unclear. We retrospectively analyzed neonates and infants with TAM enrolled in the nationwide Japan Children's Cancer Group TAM-10 study to evaluate the efficacy and safety of ExT and CS. Among 167 patients enrolled in the trial, 15 received ExT, 15 received CS, and 5 received both; 17 of these patients also received LDAC. ExT rapidly reduced white blood cell (WBC) counts and liver enzymes within 24-48 h, while CS decreased WBC counts within one week. No serious adverse events were documented as being directly attributable to either intervention. Despite these short-term effects, neither ExT nor CS significantly improved early mortality or long-term outcomes in the overall cohort. Notably, among patients with hyperleukocytosis who did not receive LDAC, noncytotoxic interventions were associated with a lower incidence of early mortality, although the sample size was limited. Our findings suggest that although ExT and CS do not significantly improve overall outcomes, they are feasible and generally safe and may serve as bridging therapies for selected patients with severe TAM who are ineligible for LDAC at diagnosis. Further studies are warranted to define optimal indications for these noncytotoxic strategies. What is Known: • Transient abnormal myelopoiesis (TAM) in Down syndrome usually resolves spontaneously, but 10%-20% of affected neonates experience early mortality. • Low-dose cytarabine (LDAC) reduces early mortality in life-threatening TAM, whereas the roles of exchange transfusion (ExT) and systemic corticosteroids (CS) remain unclear. What is New: • In the nationwide TAM-10 study cohort, ExT and CS were associated with short-term hematologic effects without serious adverse events directly attributed to either intervention. • These noncytotoxic interventions did not improve overall outcomes, but may serve as bridging therapies for selected patients with severe TAM who are ineligible for LDAC.