Excellent long-term survival of children with Down syndrome and standard-risk ALL: a report from the Children’s Oncology Group

Yousif Matloub, Karen R. Rabin, Lingyun Ji, Meenakshi Devidas, Johann Hitzler, Xinxin Xu, Bruce C. Bostrom, Linda C. Stork, Naomi Winick, Julie M. Gastier-Foster, Nyla A. Heerema, Eileen Stonerock, William L. Carroll, Stephen P. Hunger and Paul S. Gaynon

Key Points

  • Use of escalating IV MTX in children with DS and ALL was well tolerated and led to excellent long-term outcomes.


The Children’s Cancer Group 1991 study was a clinical trial for children with National Cancer Institute standard-risk acute lymphoblastic leukemia (ALL). This trial demonstrated that 5 doses of vincristine and escalating IV methotrexate (MTX) without leucovorin rescue in the interim maintenance (IM) phases resulted in superior event-free survival (EFS) when compared with 2 doses of vincristine, oral (PO) MTX, PO mercaptopurine, and dexamethasone. This report describes a favorable outcome of this regimen in patients with Down syndrome (DS). Forty-four patients with DS were randomized to the arms containing PO MTX during IM, and 31 to those containing IV MTX. Ten-year EFS rates for patients with DS randomized to IV MTX vs PO MTX were 94.4% ± 5.4% vs 81.5% ± 6.6%, respectively. IV methotrexate with strict escalation parameters, as given in this study, was well tolerated, although the mean total tolerated dose received was lower in patients with DS than in those without DS. There was no increase in hepatic toxicity, systemic infections, or treatment-related deaths in patients with DS during IM on either the IV or PO MTX arms, as compared with those without DS. The incidence of mucositis was increased in patients with DS as compared with patients without DS, particularly among patients who received IV MTX. This trial was registered at as #NCT00005945.

  • Submitted January 22, 2019.
  • Accepted March 25, 2019.
View Full Text