BACKGROUND: Although mercaptopurine (MP) is conventionally used to treat childhood acute lymphoblastic leukemia (ALL), thioguanine (TG) is a more potent thiopurine in vitro and, when administered orally to patients, achieves cytotoxic drug concentrations in the cerebrospinal fluid (CSF). We performed a pilot study incorporating oral and 24-hr continuous IV infusion (CIVI) TG in children with newly diagnosed standard-risk ALL. PROCEDURE: Children with newly diagnosed standard-risk ALL (age 1-10 years, WBC<50 k) were eligible. Multi-agent chemotherapy was patterned after the Children's Cancer Group (CCG) 105 trial, with the addition of CIVI-TG (480 mg/m2) during consolidation, interim maintenance and maintenance, and substitution of oral TG (60 mg/m2/day) for oral MP during maintenance. RESULTS: Fifty-eight patients (31 female), median age 4.3 years, were enrolled. At 8 years, the relapse-free and overall survival probabilities were 83% and 88%. There were no CNS relapses. Six patients (five males) experienced reversible veno-occlusive disease (VOD) while receiving oral TG, and the study was amended to discontinue TG, changing all patients to oral MP. Red cell TG nucleotide concentrations during oral TG averaged 95 ng (570 pmol)/8x10(8) RBC, greater than concentrations reported with oral MP. CONCLUSION: Although the absence of CNS relapses in this pilot study suggests that TG may contribute to the prevention of CNS recurrences, the development of VOD negatively impacts the risk:benefit ratio of substituting TG for MP. Copyright (c) 2006 Wiley-Liss, Inc.
BACKGROUND: Although mercaptopurine (MP) is conventionally used to treat childhood acute lymphoblastic leukemia (ALL), thioguanine (TG) is a more potent thiopurine in vitro and, when administered orally to patients, achieves cytotoxic drug concentrations in the cerebrospinal fluid (CSF). We performed a pilot study incorporating oral and 24-hr continuous IV infusion (CIVI) TG in children with newly diagnosed standard-risk ALL. PROCEDURE: Children with newly diagnosed standard-risk ALL (age 1-10 years, WBC<50 k) were eligible. Multi-agent chemotherapy was patterned after the Children's Cancer Group (CCG) 105 trial, with the addition of CIVI-TG (480 mg/m2) during consolidation, interim maintenance and maintenance, and substitution of oral TG (60 mg/m2/day) for oral MP during maintenance. RESULTS: Fifty-eight patients (31 female), median age 4.3 years, were enrolled. At 8 years, the relapse-free and overall survival probabilities were 83% and 88%. There were no CNS relapses. Six patients (five males) experienced reversible veno-occlusive disease (VOD) while receiving oral TG, and the study was amended to discontinue TG, changing all patients to oral MP. Red cell TG nucleotide concentrations during oral TG averaged 95 ng (570 pmol)/8x10(8) RBC, greater than concentrations reported with oral MP. CONCLUSION: Although the absence of CNS relapses in this pilot study suggests that TG may contribute to the prevention of CNS recurrences, the development of VOD negatively impacts the risk:benefit ratio of substituting TG for MP. Copyright (c) 2006 Wiley-Liss, Inc.
Authors: Linda C 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 Journal: Blood Date: 2010-02-01 Impact factor: 22.113
Authors: K Schmiegelow; E Forestier; J Kristinsson; S Söderhäll; K Vettenranta; R Weinshilboum; F Wesenberg Journal: Leukemia Date: 2008-11-06 Impact factor: 11.528
Authors: Lisa Wray; Marijana Vujkovic; Thomas McWilliams; Shannon Cannon; Meenakshi Devidas; Linda Stork; Richard Aplenc Journal: Pediatr Blood Cancer Date: 2014-04-16 Impact factor: 3.167