Clinical implications of cytogenetic heterogeneity in Philadelphia chromosome positive (Ph++) adult B cell acute lymPh+oblastic leukemia following tyrosine kinase inhibitors and chemotherapy regimens

Poonam Jain, Jun Gu, Rashmi Kanagal-Shamanna, Zhenya Tang, Keyur P. Patel, Hui Yao, Lianghua Fang, Hai Yan Bao, Ching Hua Liu, Pei Lin, L. Jeffrey Medeiros, Xinyan Lu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

We retrospectively studied a cohort of 144 adults with Philadelphia chromosome/BCR-ABL1 positive B acute lymphoblastic leukemia (Ph + B-ALL) to assess the clinical implications of cytogenetic heterogeneity in this disease. The study group included 85 men and 59 women that were sorted into 6 subgroups based on karyotypic findings in the stemline as follows: 32 patients with t(9;22) as a sole aberration, 23 with t(9;22) plus 1 additional chromosomal abnormality (ACA), 26 with t(9;22) as part of a complex karyotype, 18 showing a variant-/complex- t(9;22), 30 with t(9;22) as the stemline with ACAs in the sideline(s), and 15 patients who had the t(9;22) and hyperdiploidy. In 89 patients 1 clone was identified; 41 had 2 clones and 14 had ≥ 3 clone(s). The median overall survival (OS) was 25.6 months and the median relapse-free survival (RFS) was 20.6 months. Patients with variant-/complex- t(9;22) had poorer OS and RFS when compared with all other subgroups combined (P = 0.0018 and P = 0.0049, respectively). In addition, patients with ≥ 2 clones had worse OS and RFS than patients with 1 clone (P = 0.0179 and P = 0.0429, respectively). Multivariate analysis confirmed that variant-/complex-t(9;22) and clone number are independent risk factors. We suggest that conventional chromosomal analysis is of clinical importance for risk stratification of B-ALL patients.

Original languageEnglish (US)
Article number106176
JournalLeukemia Research
Volume84
DOIs
StatePublished - Sep 2019

Keywords

  • B cell acute lymphoblastic leukemia
  • B-ALL
  • BCR-ABL1
  • Complex t(9, 22)
  • Cytogenetic heterogeneity
  • Overall survival (OS)
  • Philadelphia chromosome (Ph)
  • Relapse-free survival (RFS)
  • Tyrosine kinase inhibitor (TKI)
  • Variant t(9, 22)
  • additional chromosomal abnormalities (ACAs)

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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