Open AccessAcute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes
Author(s) -
Stavroula Anastasopoulou,
Ruby I. Nielsen,
Bodil AlsNielsen,
Joanna Banerjee,
Mats Eriksson,
Marianne Helenius,
Mats Heyman,
Inga María Jóhannsdóttir,
Ólafur G. Jónsson,
Stuart MacGregor,
Marion K. Mateos,
Chelsea Mayoh,
Sirje Mikkel,
Ida Hed Myrberg,
Riitta Niinimäki,
Kjeld Schmiegelow,
Mervi Taskinen,
Goda Vaitkevičienė,
Anna Warnqvist,
Benjamin Ole Wolthers,
Arja HarilaSaari,
Susanna Ranta
Publication year - 2022
Publication title -
haematologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.782
H-Index - 142
eISSN - 1592-8721
pISSN - 0390-6078
DOI - 10.3324/haematol.2021.280016
Subject(s) - medicine , toxicity , single nucleotide polymorphism , cohort , cumulative incidence , hematology , snp , oncology , genotype , biology , genetics , gene
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 (GWAS), and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1 166 patients. Findings were validated in an Australian independent cohort of children with ALL (n=797) where 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 with cumulative incidence of 8.7% (95% CI: 7.31–10.20) at 12 months from diagnosis. Patients aged ≥10 years had higher risk of CNS toxicity than younger patients (16.3% vs 7.4%; p