title: Treatment and prognostic impact of transient leukemia in neonates with Down syndrome.
abstract: Approximately 10% of the neonates with Down syndrome (DS) exhibit a unique transient leukemia (TL). Though TL resolves spontaneously in most patients, early death and development of myeloid leukemia (ML-DS) may occur. Prognostic factors as well as treatment indication are currently uncertain. To resolve that issue, we prospectively collected clinical, biologic, and treatment data of 146 patients with TL. The 5-year overall survival (OS) and event-free survival (EFS) were 85% plus or minus 3% and 63% plus or minus 4%, respectively. Multivariate analysis revealed a correlation between high white blood cell (WBC) count, ascites, preterm delivery, bleeding diatheses, failure of spontaneous remission, and the occurrence of early death. Treatment with cytarabine (0.5-1.5 mg/kg) was administered to 28 patients with high WBC count, thrombocytopenia, or liver dysfunction. The therapy had a beneficial effect on the outcome of those children with risk factors for early death (5-year EFS, 52% +/- 12% vs 28% +/- 11% [no treatment]; P = .02). Multivariate analysis demonstrated its favorable prognostic impact. A total of 29 (23%) patients with TL subsequently developed ML-DS. Patients with ML-DS with a history of TL had a significantly better 5-year EFS (91% +/- 5%) than those without documented TL (70% +/- 4%), primarily due to a lower relapse rate. A history of TL may therefore define a lower-risk ML-DS subgroup. This study was registered at www.clinicaltrials.gov as no. NCT 00111345.
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany.
authors.forename: Jan-Henning
authors.initials: JH
authors.lastname: Klusmann
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Michael
authors.initials: M
authors.lastname: Dworzak
authors.forename: Norbert
authors.initials: N
authors.lastname: Jorch
authors.forename: Claudia
authors.initials: C
authors.lastname: Langebrake
authors.forename: Arnulf
authors.initials: A
authors.lastname: Pekrun
authors.forename: Katarina
authors.initials: K
authors.lastname: Macakova-Reinhardt
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
mesh_terms: D004314:Down Syndrome / Q000150:complications / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007938:Leukemia / Q000150:complications / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy*; D008297:Male; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome