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.

Trial registration: ClinicalTrials.gov NCT00111345.

Figures

Figure 1

Event-free and overall survival in children with Down syndrome and transient leukemia.

Figure 2

Significantly impaired prognosis in children with high WBC count at diagnosis. (A) EFS. (B) Cumulative incidence of death and ML-DS.

Figure 3

Cumulative incidence of death and of ML-DS in children with TL. Patients grouped according to the appearance of (A) ascites, (B) bleeding diatheses, (C) preterm delivery, and (D) pleural effusions.

Figure 4

Outcome of patients with TL with and without treatment with low-dose cytarabine. (A) EFS of those patients with TL with high WBC count, ascites, preterm delivery, and bleeding diatheses and without spontaneous remission. (B) Cumulative incidence of death.

Figure 5

EFS in children with ML-DS and a history of TL compared with those with ML-DS and no history of TL (enrolled between 1993 and 2006).