BCR-ABL1 transcripts (MR4.5) at post-transplant 3 months as an early predictor for long-term outcomes in chronic myeloid leukemia

Korean J Intern Med. 2017 Jan;32(1):125-136. doi: 10.3904/kjim.2015.187. Epub 2016 Jun 22.

Abstract

Background/aims: The aim of this study was to identify the role of BCR-ABL1 transcript level as a predictor for post-transplant relapse and outcome in patients who underwent allogeneic stem cell transplantation (SCT) for chronic phase (CP) chronic myeloid leukemia (CML).

Methods: Of 101 patients receiving allograft in CML CP, 85 had available quantitative reverse transcriptase polymerase chain reaction data at post-transplant 3 months. These patients were divided into two groups according to molecular response (MR4.5), defined as a BCR-ABL1 transcript level ≤ 0.0032% on the international scale, at 3 months based on receiver operating characteristic curve analysis of relapse.

Results: The 4-year overall survival and event-free survival (EFS) were 80.6% and 57.3%, respectively, and the cumulative incidence of relapse at 4 years was 29.6% after a median follow-up of 126.4 months. We performed multivariate analyses including potential variables to evaluate the early predictive role of MR4.5 at 3 months and found that MR4.5 at 3 months was associated with a higher EFS (p = 0.028) and showed a trend for a lower relapse rate (p = 0.089).

Conclusions: our results imply that frequent molecular monitoring and immune suppressive therapy modulation are required for patients without reduction of BCR-ABL1 transcripts to this level after SCT.

Keywords: Allogeneic stem cell transplantation; Leukemia, myelogenous, chronic, BCR-ABL positive; Post-transplant relapse.

MeSH terms

  • Adolescent
  • Adult
  • Area Under Curve
  • Biomarkers, Tumor / genetics*
  • Disease-Free Survival
  • Drug Therapy, Combination
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Graft vs Host Disease / etiology
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / surgery*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Proportional Hazards Models
  • ROC Curve
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Stem Cell Transplantation* / adverse effects
  • Stem Cell Transplantation* / mortality
  • Time Factors
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • BCR-ABL1 fusion protein, human
  • Biomarkers, Tumor
  • Immunosuppressive Agents
  • Fusion Proteins, bcr-abl