Clinical-biological Characteristics and Poor Predictive Value of Early
Treatment Response in Pediatric Acute Lymphoblastic Leukemia with CDKN2A
Gene Deletion Treat with CCLG-ALL 2015 protocol
Abstract
Background: Deletion of cyclin-dependent kinase inhibitor 2A (CDKN2A) is
prevalent in pediatric acute lymphoblastic leukemia (ALL) and the
prognostic importance of CDKN2A deletion is still controversial.
Procedure: A total of newly diagnosed 655 pediatric ALL cases were
treated with Chinese Children’s Leukemia Group-acute lymphoblastic
leukemia 2015 (CCLG-ALL 2015) protocol[1]. We investigated the
difference among B-ALL and T-ALL patients with CDKN2A deletion for
clinical characteristics at diagnosis, immunophenotype, risk
stratification, cytogenetic risk group, and early treatment responses.We
also analyzed the prognostic markers for event-free survival(EFS) in
CDKN2A-deleted patients. Result: The incidence of CDKN2A gene deletion
was presented in 14.6% (87/595) of B-ALL subgroup and 40.0% (24/60) of
T-ALL subgroup. T-ALL subgroup was characterized by a higher male/female
ratio, a higher proportion of older children (>10 years
old) and WBC counts of greater than 50x109/L compared to
B-ALL(P<0.05). In the univariate analysis, CNS 2, cytogenetic
risk groups, prednisone poor responders (PPR), poor early response
(PER), and MRD≥0.01% at day 46 (P<0.05) were associated with
a poor event-free survival. Multivariable analysis revealed that PPR and
MRD≥0.01% at day 46 were independent inferior prognostic factors for
event-free survival(P<0.05). Conclusions: The incidence of
CDKN2A deletion was more prevalent in T-ALL. CDKN2A deletion was
significantly more prevalent in older (>10 years old) boys
with leukocyte counts of greater than 50x109/L among T-ALL. PPR and
MRD≥0.01% at day 46 were an independent prognostic factor for EFS in
pediatric CDKN2A-deleted ALL.