H Xiong, SY Ha, AKS Chiang, DKL Cheuk, LK Zeng, GCF Chan

Abstract

Background: Neonates with constitutional trisomy 21 are predisposed to develop transient myeloproliferative disease (TMD). TMD is characterised by a rapid accumulation of blast cells during the first few days of life followed by spontaneous resolution. Around 20% to 30% of them subsequently evolve into acute megakaryoblastic leukaemia (AMKL or FAB M7). Objective: To examine the natural history and biological characteristics of neonatal TMD, the clinical characteristic associated with subsequent AMKL, and the prognosis of AMKL with constitutional trisomy 21 in Chinese children. Methods: We retrospectively reviewed the charts of 4 neonates with trisomy 21 and TMD and compared them with that of the literature. Results: Trisomy 21 was the only cytogenetic abnormality identified in the blast cells of the 4 patients. In all of the neonates, peripheral blast cells cleared spontaneously, blood counts normalised and complete remission ensued without chemotherapy. Three of the 4 neonates developed AMKL at a mean age of 15 months of age and they were treated with chemotherapy. All achieved and maintained complete remission for a mean duration of 8 years (range 6.1-10.4 years). The remaining patient was found to have trisomy 21 only in the blast cells and he has normal phenotype without any Down's stigmata. Conclusion: Neonatal TMD is a unique clinical syndrome associated with spontaneous remission but with a high chance of developing AMKL subsequently. Interestingly, such AMKL are chemosensitive and can achieve long term remission with chemotherapy alone. Further research should focus on the role of genetic interactions of trisomy 21 in leukaemogenesis and on identifying specific therapeutic targets. Multicentre collaborative study has been conducting and risk stratification approach has been applied to minimise the therapy related toxicity currently.