Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia

Report of the Children's Oncology Group CCG-1952 clinical trial

Linda Stork, Yousif Matloub, Emmett Broxson, Mei La, Rochelle Yanofsky, Harland Sather, Ray Hutchinson, Nyla A. Heerema, April D. Sorrell, Margaret Masterson, Archie Bleyer, Paul S. Gaynon

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Abstract

The Children's Cancer Group 1952 (CCG-1952) clinical trial studied the substitution of oral 6-thioguanine (TG) for 6-mercaptopurine (MP) and triple intrathecal therapy (ITT) for intrathecal methotrexate (IT-MTX) in the treatment of standard-risk acute lymphoblastic leukemia. After remission induction, 2027 patients were randomized to receive MP (n = 1010) or TG (n = 1017) and IT-MTX (n = 1018) or ITT (n = 1009). The results of the thiopurine comparison are as follows. The estimated 7-year event-free survival (EFS) for subjects randomized to TG was 84.1% (± 1.8%) and to MP was 79.0% (± 2.1%; P ± .004 log rank), although overall survival was 91.9% (± 1.4%) and 91.2% (± 1.5%), respectively (P = .6 log rank). The TG starting dose was reduced from 60 to 50 mg/m2 per day after recognition of hepatic veno-occlusive disease (VOD). A total of 257 patients on TG (25%) developed VOD or disproportionate thrombocytopenia and switched to MP. Once portal hypertension occurred, all subjects on TG were changed to MP. The benefit of randomization to TG over MP, as measured by EFS, was evident primarily in boys who began TG at 60 mg/m2 (relative hazard rate [RHR] 0.65, P = .002). The toxicities of TG preclude its protracted use as given in this study. This study is registered at http://clinicaltrials.gov as NCT00002744.

Original languageEnglish (US)
Pages (from-to)2740-2748
Number of pages9
JournalBlood
Volume115
Issue number14
DOIs
StatePublished - Apr 8 2010

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Thioguanine
6-Mercaptopurine
Oncology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Clinical Trials
Neoplasms
Methotrexate
Disease-Free Survival
Hepatic Veno-Occlusive Disease
Remission Induction
Portal Hypertension
Random Allocation
Thrombocytopenia
Toxicity
Hazards
Substitution reactions
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia : Report of the Children's Oncology Group CCG-1952 clinical trial. / Stork, Linda; Matloub, Yousif; Broxson, Emmett; La, Mei; Yanofsky, Rochelle; Sather, Harland; Hutchinson, Ray; Heerema, Nyla A.; Sorrell, April D.; Masterson, Margaret; Bleyer, Archie; Gaynon, Paul S.

In: Blood, Vol. 115, No. 14, 08.04.2010, p. 2740-2748.

Research output: Contribution to journalArticle

Stork, L, Matloub, Y, Broxson, E, La, M, Yanofsky, R, Sather, H, Hutchinson, R, Heerema, NA, Sorrell, AD, Masterson, M, Bleyer, A & Gaynon, PS 2010, 'Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: Report of the Children's Oncology Group CCG-1952 clinical trial', Blood, vol. 115, no. 14, pp. 2740-2748. https://doi.org/10.1182/blood-2009-07-230656
Stork, Linda ; Matloub, Yousif ; Broxson, Emmett ; La, Mei ; Yanofsky, Rochelle ; Sather, Harland ; Hutchinson, Ray ; Heerema, Nyla A. ; Sorrell, April D. ; Masterson, Margaret ; Bleyer, Archie ; Gaynon, Paul S. / Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia : Report of the Children's Oncology Group CCG-1952 clinical trial. In: Blood. 2010 ; Vol. 115, No. 14. pp. 2740-2748.
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abstract = "The Children's Cancer Group 1952 (CCG-1952) clinical trial studied the substitution of oral 6-thioguanine (TG) for 6-mercaptopurine (MP) and triple intrathecal therapy (ITT) for intrathecal methotrexate (IT-MTX) in the treatment of standard-risk acute lymphoblastic leukemia. After remission induction, 2027 patients were randomized to receive MP (n = 1010) or TG (n = 1017) and IT-MTX (n = 1018) or ITT (n = 1009). The results of the thiopurine comparison are as follows. The estimated 7-year event-free survival (EFS) for subjects randomized to TG was 84.1{\%} (± 1.8{\%}) and to MP was 79.0{\%} (± 2.1{\%}; P ± .004 log rank), although overall survival was 91.9{\%} (± 1.4{\%}) and 91.2{\%} (± 1.5{\%}), respectively (P = .6 log rank). The TG starting dose was reduced from 60 to 50 mg/m2 per day after recognition of hepatic veno-occlusive disease (VOD). A total of 257 patients on TG (25{\%}) developed VOD or disproportionate thrombocytopenia and switched to MP. Once portal hypertension occurred, all subjects on TG were changed to MP. The benefit of randomization to TG over MP, as measured by EFS, was evident primarily in boys who began TG at 60 mg/m2 (relative hazard rate [RHR] 0.65, P = .002). The toxicities of TG preclude its protracted use as given in this study. This study is registered at http://clinicaltrials.gov as NCT00002744.",
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AU - Sather, Harland

AU - Hutchinson, Ray

AU - Heerema, Nyla A.

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AU - Bleyer, Archie

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