Halving Time of BCR-ABL1 in Chronic Myeloid Leukemia: Is It Better Than Day-90 Value-A Multicenter Study From South India

Clin Lymphoma Myeloma Leuk. 2020 May;20(5):e205-e211. doi: 10.1016/j.clml.2019.09.606. Epub 2019 Sep 30.

Abstract

Background: The 90-day BCR-ABL1 (breakpoint cluster region-Abelson 1) level has been one of the accepted milestones for predicting the molecular response in patients with chronic myeloid leukemia (CML). The rate of decline in BCR-ABL1 has been considered a better predictor of the response but has not been uniformly accepted. A paucity of evidence is available to predict the accuracy of the rate of decline in the Indian context. Therefore, we tested the accuracy of the rate of decline of BCR-ABL1 in predicting the molecular response compared with the single 90-day values in a retrospective cohort study of selected cancer centers in south India.

Methods and materials: Patients with chronic-phase CML diagnosed from January 2013 to December 2018, the serial BCR-ABL1 levels were estimated at 0, 45, and 90 days, 6 months, and 1 year. Data on patient demographics, risk stratification assessed using the Sokal and EUTOS (European Treatment and Outcome Study) scores were extracted using a mobile-based data capture tool from the medical records of the enrolled patients. The halving time, determined by log reduction, was compared with the 90-day BCR-ABL1 values using the receiver operating characteristic curve for the major and complete molecular response at 6 months and 1 year as standards. Accuracy was determined from the area under the curve. The cutoff for the halving time was chosen to balance the sensitivity and specificity.

Results: The rate of decline had more predictive accuracy compared with the 90-day BCR-ABL1 values (area under the curve for rate of decline, 0.83; 90-day, 0.80). A halving time of < 20 days identified 95% of the patients who had achieved major molecular response at 12 months compared with 80% using the single 90-day BCR-ABL1 response.

Conclusions: The halving time of BCR-ABL1 appears promising as a predictor of the outcomes for patients with CML.

Keywords: CML; Collaborative Medical Oncology Group; Indian data; Molecular response; Structured Operational Research and Training Initiative.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Disease-Free Survival
  • Female
  • Fusion Proteins, bcr-abl / metabolism*
  • Humans
  • India / epidemiology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / mortality
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / therapy
  • Male
  • Middle Aged
  • Survival Rate

Substances

  • BCR-ABL1 fusion protein, human
  • Fusion Proteins, bcr-abl