Outcome of TCF3-PBX1 positive pediatric acute lymphoblastic leukemia patients in Japan: a collaborative study of Japan Association of Childhood Leukemia Study (JACLS) and Children's Cancer and Leukemia Study Group (CCLSG)

Cancer Med. 2014 Jun;3(3):623-31. doi: 10.1002/cam4.221. Epub 2014 Feb 28.

Abstract

This study reviewed the clinical characteristics of 112 pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients with TCF3-PBX1 fusion treated according to the Japan Association of Childhood Leukemia Study (JACLS) ALL02 protocol (n = 82) and Children's Cancer and Leukemia Study Group (CCLSG) ALL 2004 protocol (n = 30). The 3-year event-free survival (EFS) and overall survival (OS) rates were 85.4 ± 3.9% and 89.0 ± 3.5% in JACLS cohort, and the 5-year EFS and OS were 82.8 ± 7.0% and 86.3 ± 6.4% in CCLSG cohort, respectively, which are comparable to those reported in western countries. Conventional prognostic factors such as age at onset, initial white blood cell count, and National Cancer Institute risk have also no impact on OS in both cohorts. Surprisingly, the pattern of relapse in JACLS cohort, 9 of 82 patients, was unique: eight of nine patients relapsed during the maintenance phase and one patient had primary induction failure. However, bone marrow status and assessment of minimal residual disease on days 15 and 33 did not identify those patients. Interestingly, the two patients with IKZF1 deletion eventually relapsed in JACLS cohort, as did one patient in CCLSG cohort. International collaborative study of larger cohort is warranted to clarify the impact of the IKZF1 deletion on the poor outcome of TCF3-PBX1 positive BCP-ALL.

Keywords: IKZF1 deletion; TCF3-PBX1; pediatric acute lymphoblastic leukemia.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Female
  • Humans
  • Ikaros Transcription Factor / genetics
  • Infant
  • Japan
  • Male
  • Oncogene Proteins, Fusion / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis*
  • Sequence Deletion
  • Tumor Suppressor Protein p53 / genetics

Substances

  • IKZF1 protein, human
  • Oncogene Proteins, Fusion
  • TCF3-PBX1 fusion protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Ikaros Transcription Factor