Peripheral blood monitoring of chronic myeloid leukemia during treatment with imatinib, second-line agents, and beyond

Cancer. 2011 Mar 15;117(6):1245-52. doi: 10.1002/cncr.25678. Epub 2010 Nov 2.

Abstract

Background: The current study was conducted to compare simultaneously obtained bone marrow (BM) cytogenetics (CTG), peripheral blood (PB) and BM fluorescence in situ hybridization (FISH), and quantitative real-time polymerase chain reaction (Q-PCR) for BCR-ABL1 in monitoring response to treatment with tyrosine kinase inhibitors and homoharringtonine (HHT) in patients with chronic myeloid leukemia (CML).

Methods: PB and BM FISH (n = 112 samples) and/or Q-PCR (n = 132 samples) for BCR-ABL1 were simultaneously obtained in 70 patients with Philadelphia chromosome-positive (Ph+) CML in chronic (68%), accelerated (16%), and blast phase (16%) before the initiation of therapy and during the course of treatment with imatinib (IM) (n = 40 patients), dasatinib (n = 20 patients), nilotinib (n = 4 patients), bosutinib (n = 18 patients), or HHT (n = 4 patients) for patients with newly diagnosed (n = 13 patients), IM-sensitive (n = 34 patients), IM-resistant (n = 30 patients), or IM-intolerant (n = 9 patients) disease. Eighteen patients were found to have Ph+ variants or karyotypic abnormalities in addition to the Ph+.

Results: Excellent correlations (r) were observed between PB and BM FISH (r = 0.95) and PB and BM Q-PCR (r = 0.87), as well as BM CTG and PB FISH (r = 0.89) and PB Q-PCR (r = 0.82). This correlation was not affected by the presence of the Ph+ variant or additional chromosomal abnormalities, the presence of ABL1 kinase domain mutations, phase of the disease, or treatment.

Conclusions: PB FISH and Q-PCR appear to be reliable methods with which to monitor response to modern therapy in patients with all phases of CML.

Publication types

  • Evaluation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Benzamides
  • Chemotherapy, Adjuvant
  • Cytogenetic Analysis / economics
  • Cytogenetic Analysis / methods
  • Drug Administration Schedule
  • Female
  • Hematologic Tests / methods
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Male
  • Middle Aged
  • Monitoring, Physiologic / economics
  • Monitoring, Physiologic / methods
  • Neoplasm Staging / economics
  • Neoplasm Staging / methods
  • Piperazines / therapeutic use*
  • Polymerase Chain Reaction / methods
  • Prognosis
  • Pyrimidines / therapeutic use*
  • Retrospective Studies
  • Young Adult

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate