Sensitive Replicate Real-Time Quantitative PCR of BCR-ABL Shows Deep Molecular Responses in Long-Term Post-Allogeneic Stem Cell Transplantation Chronic Myeloid Leukemia Patients

Biol Blood Marrow Transplant. 2015 Oct;21(10):1852-5. doi: 10.1016/j.bbmt.2015.06.018. Epub 2015 Jul 4.

Abstract

Real-time quantitative PCR (RT-qPCR) is commonly used for follow-up of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors, but its current sensitivity does not allow detection of very low BCR-ABL levels. Therefore RT-qPCR negativity is not synonymous with complete molecular response. Replicate RT-qPCR had shown increased sensitivity in tyrosine kinase inhibitor-treated patients and was, therefore, used here to evaluate whether RT-qPCR-negative post-allogeneic stem cell transplantation (SCT) patients harbor detectable disease. Samples from 12 patients were tested at 2 time points using 82 replicates of BCR-ABL RT-qPCR. One patient (38 months after SCT) had detectable transcripts at baseline and none at the follow-up test, done at a median of 107 months after SCT. This suggests cure from CML in the majority of allogeneic SCT patients who have no transcripts detectable by replicate RT-qPCR for BCR-ABL.

Keywords: Chronic myeloid leukemia; Quantitative PCR; Stem cell transplantation.

MeSH terms

  • Adult
  • Allografts
  • Biomarkers, Tumor / genetics*
  • Drug Resistance, Neoplasm
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / genetics*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Leukemia, Myeloid, Accelerated Phase / genetics
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm, Residual
  • Protein Kinase Inhibitors / therapeutic use
  • RNA, Messenger / blood
  • RNA, Messenger / genetics
  • RNA, Neoplasm / blood
  • RNA, Neoplasm / genetics
  • Real-Time Polymerase Chain Reaction / methods*
  • Recurrence
  • Remission Induction
  • Sensitivity and Specificity
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • RNA, Neoplasm
  • Fusion Proteins, bcr-abl