Predicting cytokine storms: it’s about density mosaicism for Hsa21, confirming that phenotypically normal neonates with hematologic findings consistent with TMD should be screened for trisomy 21 because Gamis and colleagues’ study confirms others indicating they are similarly at risk of ML-DS. 1, 4, 10 More than 75% of infants underwent bone marrow examination. Because it is unclear what additional information was obtained, it could be argued that marrow examination is unnecessary in infants with trisomy 21 where clinical and hematologic features are typical of TMD, particularly where GATA1 mutations confirm a (pre) leukemic clone. 7, 8, 10

An important dilemma in TMD management is identifying which infants will benefit from treatment and what treatment is most effective in the short-and long-term. Gamis and colleagues approached the first question using prospectively defined criteria for the presence of one or more life-threatening symptoms (LTS), including hepatic dysfunction, hydrops fetalis, or blast count (100 000/L), as sole criteria for instituting treatment at the physician’s discretion. 1 Almost half of those with LTS treated according to the guidelines (13/29) succumbed to TMD or treatment complications. By contrast, TMD resolved completely without treatment in all patients without LTS, as found previously where similar treatment guidelines were used. 4 These data support the conclusion that neonates without LTS (at diagnosis or while hematologic evidence of TMD persists) can safely be monitored without treatment because their outcome is favorable.