Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: Results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group

Yousif Matloub, Susan Lindemulder, Paul S. Gaynon, Harland Sather, Mei La, Emmett Broxson, Rochelle Yanofsky, Raymond Hutchinson, Nyla A. Heerema, James Nachman, Marilyn Blake, Linda M. Wells, April D. Sorrell, Margaret Masterson, John F. Kelleher, Linda Stork

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Abstract

The Children's Cancer Group (CCG) 1952 clinical trial for children with standardrisk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT)methotrexate (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate [HSS]) as presymptomatic central nervous system (CNS) treatment. Following remission induction, 1018 patients were randomized to receive IT MTX and 1009 ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and age younger than 2 or older than 6 years as significant predictors of isolated CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are 3.4% ± 1.0% for ITT and 5.9% ± 1.2% for IT MTX; P = .004. Significantly more relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX, particularly among patients with T-cell phenotype or day 14 BM aspirate containing 5% to 25% blasts. Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7% ± 1.9% and 82.5% ± 1.8%, respectively (P = .3). Because the salvage rate after BM relapse is inferior to that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3% ± 1.5% versus 94.4% ± 1.1% for IT MTX (P = .01). It appears that ITT improves presymptomatic CNS treatment but does not improve overall outcome.

Original languageEnglish (US)
Pages (from-to)1165-1173
Number of pages9
JournalBlood
Volume108
Issue number4
DOIs
StatePublished - Aug 15 2006
Externally publishedYes

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Oncology
Neurology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Disease-Free Survival
Central Nervous System
Recurrence
Neoplasms
Bone
Bone Marrow
Therapeutics
Remission Induction
Salvaging
Hepatomegaly
T-cells
Cytarabine
Succinic Acid
Hydrocortisone
Testis
Multivariate Analysis

ASJC Scopus subject areas

  • Hematology

Cite this

Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate : Results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group. / Matloub, Yousif; Lindemulder, Susan; Gaynon, Paul S.; Sather, Harland; La, Mei; Broxson, Emmett; Yanofsky, Rochelle; Hutchinson, Raymond; Heerema, Nyla A.; Nachman, James; Blake, Marilyn; Wells, Linda M.; Sorrell, April D.; Masterson, Margaret; Kelleher, John F.; Stork, Linda.

In: Blood, Vol. 108, No. 4, 15.08.2006, p. 1165-1173.

Research output: Contribution to journalArticle

Matloub, Yousif ; Lindemulder, Susan ; Gaynon, Paul S. ; Sather, Harland ; La, Mei ; Broxson, Emmett ; Yanofsky, Rochelle ; Hutchinson, Raymond ; Heerema, Nyla A. ; Nachman, James ; Blake, Marilyn ; Wells, Linda M. ; Sorrell, April D. ; Masterson, Margaret ; Kelleher, John F. ; Stork, Linda. / Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate : Results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group. In: Blood. 2006 ; Vol. 108, No. 4. pp. 1165-1173.
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abstract = "The Children's Cancer Group (CCG) 1952 clinical trial for children with standardrisk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT)methotrexate (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate [HSS]) as presymptomatic central nervous system (CNS) treatment. Following remission induction, 1018 patients were randomized to receive IT MTX and 1009 ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and age younger than 2 or older than 6 years as significant predictors of isolated CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are 3.4{\%} ± 1.0{\%} for ITT and 5.9{\%} ± 1.2{\%} for IT MTX; P = .004. Significantly more relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX, particularly among patients with T-cell phenotype or day 14 BM aspirate containing 5{\%} to 25{\%} blasts. Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7{\%} ± 1.9{\%} and 82.5{\%} ± 1.8{\%}, respectively (P = .3). Because the salvage rate after BM relapse is inferior to that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3{\%} ± 1.5{\%} versus 94.4{\%} ± 1.1{\%} for IT MTX (P = .01). It appears that ITT improves presymptomatic CNS treatment but does not improve overall outcome.",
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T2 - Results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group

AU - Matloub, Yousif

AU - Lindemulder, Susan

AU - Gaynon, Paul S.

AU - Sather, Harland

AU - La, Mei

AU - Broxson, Emmett

AU - Yanofsky, Rochelle

AU - Hutchinson, Raymond

AU - Heerema, Nyla A.

AU - Nachman, James

AU - Blake, Marilyn

AU - Wells, Linda M.

AU - Sorrell, April D.

AU - Masterson, Margaret

AU - Kelleher, John F.

AU - Stork, Linda

PY - 2006/8/15

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N2 - The Children's Cancer Group (CCG) 1952 clinical trial for children with standardrisk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT)methotrexate (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate [HSS]) as presymptomatic central nervous system (CNS) treatment. Following remission induction, 1018 patients were randomized to receive IT MTX and 1009 ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and age younger than 2 or older than 6 years as significant predictors of isolated CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are 3.4% ± 1.0% for ITT and 5.9% ± 1.2% for IT MTX; P = .004. Significantly more relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX, particularly among patients with T-cell phenotype or day 14 BM aspirate containing 5% to 25% blasts. Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7% ± 1.9% and 82.5% ± 1.8%, respectively (P = .3). Because the salvage rate after BM relapse is inferior to that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3% ± 1.5% versus 94.4% ± 1.1% for IT MTX (P = .01). It appears that ITT improves presymptomatic CNS treatment but does not improve overall outcome.

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