Clinicopathologic and genetic spectrum of infantile B-lymphoblastic leukemia: a multi-institutional study

Abstract

Acute lymphoblastic leukemia (ALL) in infants <1-year-old is biologically different from ALL in older children. Although KMT2A rearrangement is the predominant genetic signature in infantile B-ALL, disease course is heterogenous, behaving more aggressively in younger infants. We investigated clinicopathological differences throughout the first year to understand the transition to pediatric B-ALL. In a multi-institutional review involving four medical institutions, 54 cases of infantile B-ALL were identified. Patients were divided into congenital and non-congenital groups with multiple age subgroups. Male predominance was seen in congenital cases compared to female in non-congenital cases. There were decreasing trends of hyperleukocytosis, central nervous system involvement, KMT2A rearrangements, lineage switch, and mortality, versus increasing trends of CD10 expression and non-KMT2A abnormalities. Statistically significant differences emerged at 3 and 9 months, the latter was not previously described. Poor-prognostic risk factors decreased with age, the last trimester of infantile B-ALL essentially merging with pediatric B-ALL.

Flow cytometric analysis of cerebrospinal fluid improves detection of leukaemic blasts in infants with acute lymphoblastic leukaemia

“…Both the frequency of CNS involvement and the median CSF blast count by flow cytometry were higher in this study compared to paediatric ALL in patients aged 1–18 years 12 . This is in line with previous reports of high leukaemic cell load in the CNS in infant ALL 1,3 . The biological mechanisms leading to a high degree of CNS dissemination in infant ALL, especially in the KMT2A‐R group, have not been elucidated.…”

“…12 This is in line with previous reports of high leukaemic cell load in the CNS in infant ALL. 1,3 The biological mechanisms leading to a high degree of CNS dissemination in infant ALL, especially in the KMT2A-R group, have not been elucidated. A better understanding of the mechanisms that promote CNS dissemination in this disease entity could help develop novel therapeutic strategies for targeting CNS disease.…”

“…Acute lymphoblastic leukaemia (ALL) is rare in infants (of more than one year of age) and biologically different from ALL in older children 1 . Despite significant progress in the treatment of paediatric ALL, the prognosis of infants diagnosed with ALL remains dismal with a high risk of relapse and poor overall survival 2,3 .…”

“…Acute lymphoblastic leukaemia (ALL) is rare in infants (of more than one year of age) and biologically different from ALL in older children. 1 Despite significant progress in the treatment of paediatric ALL, the prognosis of infants diagnosed with ALL remains dismal with a high risk of relapse and poor overall survival. 2,3 Infant ALL is associated with high risk characteristics such as KMT2A rearrangement (KMT2A-R), high white blood cell count (WBC) and a high frequency of central nervous system (CNS) involvement at diagnosis.…”

Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells

“…Whereas CD19 neg relapses may be uniquely associated with immunotherapeutic pressure, B-ALL undergoing LS following conventional therapy is seen, particularly in patients with infant B-ALL with KMT2A rearrangements ( KMT2A r). 9 , 10 Unfortunately, the incidence of LS has increased with the higher use of CD19 targeting. 11 , 12 , 13 , 14 , 15 Due to the rarity, literature surrounding LS has largely been limited to descriptions within study reports or single case reports.…”