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

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.

• Authors: 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
• Journal: Leukemia research (Leuk Res) Vol. 84 Pg. 106176 (09 2019) ISSN: 1873-5835 [Electronic] England
• PMID: 31279181 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Chromosome Aberrations
• Cytogenetic Analysis
• Female
• Genetic Association Studies
• Genetic Heterogeneity
• Genetic Predisposition to Disease
• Humans
• Immunophenotyping
• In Situ Hybridization, Fluorescence
• Kaplan-Meier Estimate
• Karyotype
• Male
• Middle Aged
• Philadelphia Chromosome
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (diagnosis, drug therapy, genetics, mortality)
• Protein Kinase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome
• Young Adult