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 J Winick, Julie M. Gastier-Foster, Nyla A. Heerema, Eileen Stonerock, William L. Carroll, Stephen P. Hunger, Paul S. Gaynon

Research output: Contribution to journalArticle

Abstract

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% 6 5.4% vs 81.5% 6 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 www.clinicaltrials.gov as #NCT00005945.

Original languageEnglish (US)
Pages (from-to)1647-1656
Number of pages10
JournalBlood Advances
Volume3
Issue number11
DOIs
StatePublished - Jun 11 2019

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Down Syndrome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Survival
Maintenance
Vincristine
Disease-Free Survival
6-Mercaptopurine
Mucositis
Leucovorin
National Cancer Institute (U.S.)
Dexamethasone
Survival Rate
Clinical Trials
Liver
Incidence
Infection

ASJC Scopus subject areas

  • Medicine(all)

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Excellent long-term survival of children with Down syndrome and standard-risk ALL : A report from the Children's Oncology Group. / Matloub, Yousif; Rabin, Karen R.; Ji, Lingyun; Devidas, Meenakshi; Hitzler, Johann; Xu, Xinxin; Bostrom, Bruce C.; Stork, Linda C.; Winick, Naomi J; Gastier-Foster, Julie M.; Heerema, Nyla A.; Stonerock, Eileen; Carroll, William L.; Hunger, Stephen P.; Gaynon, Paul S.

In: Blood Advances, Vol. 3, No. 11, 11.06.2019, p. 1647-1656.

Research output: Contribution to journalArticle

Matloub, Y, Rabin, KR, Ji, L, Devidas, M, Hitzler, J, Xu, X, Bostrom, BC, Stork, LC, Winick, NJ, Gastier-Foster, JM, Heerema, NA, Stonerock, E, Carroll, WL, Hunger, SP & Gaynon, PS 2019, 'Excellent long-term survival of children with Down syndrome and standard-risk ALL: A report from the Children's Oncology Group', Blood Advances, vol. 3, no. 11, pp. 1647-1656. https://doi.org/10.1182/bloodadvances.2019032094
Matloub, Yousif ; Rabin, Karen R. ; Ji, Lingyun ; Devidas, Meenakshi ; Hitzler, Johann ; Xu, Xinxin ; Bostrom, Bruce C. ; Stork, Linda C. ; Winick, Naomi J ; Gastier-Foster, Julie M. ; Heerema, Nyla A. ; Stonerock, Eileen ; Carroll, William L. ; Hunger, Stephen P. ; Gaynon, Paul S. / Excellent long-term survival of children with Down syndrome and standard-risk ALL : A report from the Children's Oncology Group. In: Blood Advances. 2019 ; Vol. 3, No. 11. pp. 1647-1656.
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