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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1165-1173.
Prepublished online as a Blood First Edition Paper on April 11, 2006; DOI 10.1182/blood-2005-12-011809.


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CLINICAL TRIALS AND OBSERVATIONS

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, and Linda C. Stork

From the Department of Pediatrics, University of Wisconsin Children's Hospital, Madison; Department of Pediatrics, Doernbecher Children's Hospital–Oregon Health and Science University (OHSU), Portland; Department of Pediatric Hematology-Oncology, The Children's Hospital, Denver, CO; Division of Hematology-Oncology, Children's Hospital Los Angeles, CA; Children's Oncology Group–Operations Center, Arcadia, CA; Department of Hematology-Oncology, Children's Medical Center, Dayton, OH; Department of Pediatric Hematology/Oncology, CancerCare Manitoba, Winnipeg, Canada; C. S. Mott Children's Hospital, Ann Arbor, MI; Department of Cytogenetics, Ohio State University, Columbus Children's Hospital; University of Chicago Medical Center, IL; South Carolina Cancer Center, Columbia; Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick; and Department of Pediatrics, Sacred Heart Hospital, Pensacola, FL.

The Children's Cancer Group (CCG) 1952 clinical trial for children with standard-risk 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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