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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
  • +3
  • jing feng,
  • Ye Guo,
  • Wen-Yu Yang,
  • Yao Zou,
  • Xiaofan Zhu,
  • Xiaojuan Chen
jing feng
Chinese Academy of Medical Sciences Institute of Hematology and Blood Diseases Hospital
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Ye Guo
Chinese Academy of Medical Sciences Institute of Hematology and Blood Diseases Hospital
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Wen-Yu Yang
Chinese Academy of Medical Sciences Institute of Hematology and Blood Diseases Hospital
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Yao Zou
Chinese Academy of Medical Sciences Institute of Hematology and Blood Diseases Hospital
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Xiaofan Zhu
Chinese Academy of Medical Sciences Institute of Hematology and Blood Diseases Hospital
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Xiaojuan Chen
Chinese Academy of Medical Sciences Institute of Hematology and Blood Diseases Hospital
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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.