Additional Cytogenetic Abnormalities with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia on Allogeneic Stem Cell Transplantation in the Tyrosine Kinase Inhibitor Era

Biol Blood Marrow Transplant. 2018 Oct;24(10):2009-2016. doi: 10.1016/j.bbmt.2018.06.006. Epub 2018 Jun 14.

Abstract

Cytogenetic abnormalities are well known and powerful independent prognostic factors for various hematologic disorders. Although the combination of chemotherapy with tyrosine kinase inhibitor (TKI) is now considered the standard of care in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia, little is known about the impact of additional cytogenetic abnormalities (ACAs). Therefore, we retrospectively evaluated 1375 adult patients who underwent their first allogeneic hematopoietic stem cell transplantation in the TKI era. In this study, 224 patients had ACAs (16.3%). The ACAs that were seen in more than 20 cases (1.5%) were as follows: -7, der(22), der(9), +8, and +X. Overall survival at 4 years was 56.9% (95% confidence interval [CI], 49.4% to 63.7%) in the group with ACAs and 60.5% (95% CI, 57.3% to 63.5%) in the group without ACAs (P = .266). The cumulative incidence of relapse at 4 years was 28.9% (95% CI, 22.6% to 35.6%) in the group with ACAs and 21.9% (95% CI, 19.4% to 24.6%) in the group with Ph alone (P = .051). In multivariate analyses there were no statistically significant differences in the risk of overall mortality or risk of relapse between the groups with and without ACAs. In the subgroup analyses of specific ACAs, although the presence of +8 was associated with a higher relapse rate in univariate and multivariate analyses, no specific ACA was associated with poor overall survival. Further studies will be needed to verify the impact of specific ACAs on transplantation outcomes.

Keywords: Philadelphia chromosome–positive acute lymphoblastic leukemia; additional cytogenetic abnormalities; tyrosine kinase inhibitor.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Allografts
  • Chromosome Aberrations*
  • Disease-Free Survival
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Philadelphia Chromosome*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Protein Kinase Inhibitors / administration & dosage*
  • Retrospective Studies
  • Survival Rate

Substances

  • Protein Kinase Inhibitors