Fluorescent In Situ Hybridization Monitoring and Effect of Detected Early Responses in the Outcome of Patients With Chronic Phase Chronic Myeloid Leukemia: A Report From a Latin American Country

Clin Lymphoma Myeloma Leuk. 2016 Aug;16(8):453-9. doi: 10.1016/j.clml.2016.04.002. Epub 2016 May 5.

Abstract

Introduction: The cytogenetic hallmark of chronic myeloid leukemia (CML) is the Philadelphia chromosome. Monitoring the response in patients receiving therapy is a standard of care. The present study was conducted to assess the monitoring adherence and reliableness of fluorescent in situ hybridization (FISH) as a monitoring tool and the effect of a complete cytogenetic response (CCyR) assessed by FISH on the prognosis of patients in a chronic phase (CP)-CML cohort.

Materials and methods: We retrospectively analyzed the data from 63 newly diagnosed CP-CML patients treated with imatinib mesylate at a dose of 400 mg/day as frontline therapy. The clinical data and cytogenetic test results at diagnosis and during monitoring were collected. The cytogenetic monitoring adherence assessment rates were measured. A correlation between chromosome banding analysis (CBA) and FISH was performed. The CCyR assessed by FISH was defined as < 1% BCR-ABL1(+) nuclei. The Kaplan-Meier method was used for overall survival analysis and time-to-event estimates.

Results: The cytogenetic monitoring assessment adherence was 50.8% at 3 months, 93.5% at 6 months, 96.7% at 12 months, and 88.6% at 18 months. The Pearson correlation coefficient showed a significantly positive association (r = 0.84; P < .001) between CBA and FISH. The median follow-up duration after imatinib mesylate initiation was 60 months. A CCyR was achieved in 90.4% of patients within the first 18 months of therapy. At 3 months, 31 patients underwent a FISH evaluation, and 13 (41.9%) had achieved a CCyR. The patients who did not achieve a CCyR at 3 months had a significantly inferior probability of 5-year failure-free survival (38% vs. 94%; P = .001) and progression-free survival (80% vs. 100%; P = .043) compared with those with a CCyR.

Conclusion: We found improved monitoring adherence compared with the previous reports of Latin American populations. In countries with a high incidence of failure for CBA and a lack of real-time polymerase chain reaction standardization, FISH is a sensitive monitoring tool. In our cohort, patients not achieving an early CCyR, as tested by FISH, were a poor prognosis subgroup with worse rates of failure-free survival and progression-free survival.

Keywords: CP-CML; Chromosome banding analysis; Cytogenetic monitoring; FISH; Myeloproliferative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor*
  • Chromosome Banding
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • In Situ Hybridization, Fluorescence*
  • Kaplan-Meier Estimate
  • Latin America
  • Leukemia, Myeloid, Chronic-Phase / diagnosis
  • Leukemia, Myeloid, Chronic-Phase / drug therapy
  • Leukemia, Myeloid, Chronic-Phase / genetics*
  • Leukemia, Myeloid, Chronic-Phase / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Fusion Proteins, bcr-abl