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1دورية أكاديمية
المؤلفون: Stavroula Anastasopoulou, Rikke Linnemann Nielsen, Bodil Als-Nielsen, Joanna Banerjee, Mats A. Eriksson, Marianne Helenius, Mats M. Heyman, Inga Maria Johannsdottir, Olafur Gisli Jonsson, Stuart MacGregor, Marion K. Mateos, Chelsea Mayoh, Sirje Mikkel, Ida Hed Myrberg, Riitta Niinimäki, Kjeld Schmiegelow, Mervi Taskinen, Goda Vaitkeviciene, Anna Warnqvist, Benjamin Wolthers, Arja Harila-Saari, Susanna Ranta
المصدر: Haematologica, Vol 107, Iss 10 (2022)
مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5
الوصف: Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0–17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31–10.20) at 12 months from diagnosis. Patients aged ≥10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P
وصف الملف: electronic resource
العلاقة: https://haematologica.org/article/view/10591Test; https://doaj.org/toc/0390-6078Test; https://doaj.org/toc/1592-8721Test
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2دورية أكاديمية
المؤلفون: Marion K. Mateos, Glenn M. Marshall, Pasquale M. Barbaro, Michael C.J. Quinn, Carly George, Chelsea Mayoh, Rosemary Sutton, Tamas Revesz, Jodie E. Giles, Draga Barbaric, Frank Alvaro, Françoise Mechinaud, Daniel Catchpoole, John A. Lawson, Georgia Chenevix-Trench, Stuart MacGregor, Rishi S. Kotecha, Luciano Dalla-Pozza, Toby N. Trahair
المصدر: Haematologica, Vol 107, Iss 3 (2021)
مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5
الوصف: Symptomatic methotrexate-related central neurotoxicity (MTX neurotoxicity) is a severe toxicity experienced during acute lymphoblastic leukemia (ALL) therapy with potential long-term neurologic complications. Risk factors and long-term outcomes require further study. We conducted a systematic, retrospective review of 1,251 consecutive Australian children enrolled on Berlin-Frankfurt-Münster or Children's Oncology Group-based protocols between 1998-2013. Clinical risk predictors for MTX neurotoxicity were analyzed using regression. A genome-wide association study (GWAS) was performed on 48 cases and 537 controls. The incidence of MTX neurotoxicity was 7.6% (n=95 of 1,251), at a median of 4 months from ALL diagnosis and 8 days after intravenous or intrathecal MTX. Grade 3 elevation of serum aspartate aminotransferase (P=0.005, odds ratio 2.31 [range, 1.28–4.16]) in induction/consolidation was associated with MTX neurotoxicity, after accounting for the only established risk factor, age ≥10 years. Cumulative incidence of CNS relapse was increased in children where intrathecal MTX was omitted following symptomatic MTX neurotoxicity (n=48) compared to where intrathecal MTX was continued throughout therapy (n=1,174) (P=0.047). Five-year central nervous system relapse-free survival was 89.2 4.6% when intrathecal MTX was ceased compared to 95.4 0.6% when intrathecal MTX was continued. Recurrence of MTX neurotoxicity was low (12.9%) for patients whose intrathecal MTX was continued after their first episode. The GWAS identified single-nucletide polymorphism associated with MTX neurotoxicity near genes regulating neuronal growth, neuronal differentiation and cytoskeletal organization (P
وصف الملف: electronic resource
العلاقة: https://haematologica.org/article/view/10178Test; https://doaj.org/toc/0390-6078Test; https://doaj.org/toc/1592-8721Test
النص الكامل