Interpretation of cytogenetic and molecular results in patients treated for CML

Carlos E. Vigil, Elizabeth A. Griffiths, Eunice S. Wang, Meir Wetzler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The International Randomized Study of Interferon vs. STI571 (IRIS) trial that investigated the use of the tyrosine kinase inhibitor (TKI) imatinib (versus interferon) changed the treatment and outcome of chronic myeloid leukemia (CML). Long-term follow-up of IRIS patients has defined response parameters and methods of tracking residual disease with cytogenetic testing of bone marrow metaphases and molecular monitoring of BCR-ABL transcripts using quantitative reverse-transcriptase polymerase chain reaction. Cytogenetic and molecular responses are now considered useful surrogates for long-term outcome. Early and robust response to imatinib predicts positive long-term outcomes. However, 15-25% of patients fail initial treatment or become intolerant of imatinib and need increased doses or alternate treatment. Second-line treatment with the second-generation TKIs nilotinib and dasatinib have resulted in favorable rates of progression-free survival (PFS) and overall survival. Data from the ENESTnd (nilotinib) and DASISION (dasatinib) trials in newly diagnosed chronic-phase CML patients demonstrated more robust and rapid complete cytogenetic (77-80%) and major molecular responses (43-46%) at 12. months compared with imatinib (65-66% and 22-28%). The relationship between a complete cytogenetic response at 12. months and long-term PFS supports a role for second-generation TKIs as first-line treatment of newly diagnosed chronic-phase CML.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalBlood Reviews
Volume25
Issue number3
DOIs
StatePublished - May 2011
Externally publishedYes

Keywords

  • Chronic myeloid leukemia
  • Cytogenetic response
  • Dasatinib
  • Imatinib
  • Molecular response
  • Nilotinib

ASJC Scopus subject areas

  • Hematology
  • Oncology

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