Transient Myeloproliferative Disorder in Neonates With and Without Down Syndrome

Abstract

Transient myeloproliferative disorder (TMD) in newborns with Down syndrome (DS) has been well described. We report 4 newborns, 2 with DS and 2 without DS, who developed TMD. One newborn with DS developed multiorgan failure and died despite treatment with low-dose cytarabine. In 3 newborns, the TMD resolved spontaneously. Two of these patients, 1 with and 1 without DS developed leukemia on subsequent follow-up and were treated successfully. We reviewed the clinical and laboratory data on 14 non-DS infants with TMD reported in the literature. According to limited data, these patients are more likely to develop leukemia than DS patients, however their outcome is better.

Origin of Leukemia in Children with Down Syndrome

“…Trisomy 21, however, may only be present in a proportion of tissues including the hematopoietic one in infants, with TL lacking the typical features of DS (trisomy 21 mosaicism) (Zipursky 2003 ;Gamis et al 2011 ). In fact, trisomy 21 may be confi ned only to a proportion of hematopoietic cells, including normal cells and the TL blast population, or exclusively to the population of TL blasts (Apollonsky et al 2008 ;Ono et al 2015 ;Tsai et al 2011 ). Trisomy may involve the entire chromosome 21 or a specifi c part (segmental trisomy 21) (Korbel et al 2009 ;Korenberg et al 1994 ).…”

Acute Megakaryoblastic Leukemia Without GATA1 Mutation After Transient Myeloproliferative Disorder in an Infant Without Down Syndrome

“…7 A retrospective review reported that five of 16 patients with TMD without DS developed subsequent leukemia, three developed AMKL, and two developed non-AMKL acute myeloid leukemia, but patients were not checked for the presence of GATA1 mutations. 4 Our patient developed AMKL subsequent to TMD. She had high WBC with TMD, spontaneous remission, and reappearance of megakaryoblasts with lower WBC.…”

“…TMD also occurs in children without DS who have either mosaicism for trisomy 21 or normal karyotype. 4 The frequency and pathogenesis of TMD and subsequent AMKL in these children is not well known because TMD may go undetected.…”

“…Cytogenetic analysis revealed karyotype 47,XX,ϩ21[16]/46,XX [4] (Fig 2A, arrow indicates trisomy 21). Fluorescence in situ hybridization using ETO-AML1 probes showed a normal pattern of signal distribution in buccal epithelial cells, without evidence of an extra AML1 signal.…”

Transient abnormal myelopoiesis in a cytogenetically normal neonate

“…Transient abnormal myelopoiesis and subsequent AMKL with acquired trisomy 21 has also been observed in phenotypically normal and/or cytogenetically normal infants albeit much less commonly [5][6][7]. In such cases, the status of GATA1 has been rarely characterized [8][9][10][11][12].…”