Estimations of BCR-ABL/ABL transcripts by quantitative PCR in chronic myeloid leukaemia after allogeneic bone marrow transplantation and donor lymphocyte infusion

Leuk Res. 2002 Feb;26(2):129-41. doi: 10.1016/s0145-2126(01)00109-6.

Abstract

Serial assays of qualitative (multiplex and nested) and quantitative PCR were carried out for detecting and estimating the level of BCR-ABL transcripts in 39 CML patients following bone marrow transplantation. Seven of these patients, who received donor lymphocyte infusions (DLIs) following to relapse, were also monitored. Quantitative estimates of BCR-ABL transcripts were obtained by co-amplification with a competitor sequence. Estimates of ABL transcripts were used, an internal control and the ratio BCR-ABL/ABL was thus estimated for evaluating the kinetics of residual clones. Twenty four patients were followed shortly after BMT; two of these patients were in cytogenetic relapse coexisting with very high BCR-ABL levels while other 22 were in clinical, haematologic and cytogenetic remission 2-42 months after BMT. In this latter group, seven patients showed a favourable clinical-haematological progression in association with molecular remission while in 14 patients quantitative PCR assays indicated molecular relapse that was not associated with an early cytogenetic-haematologic relapse. BCR-ABL/ABL levels could not be correlated with presence of GVHD in 24 patients after BMT. In all seven patients treated with DLI, high levels of transcripts were detected at least 4 months before the appearance of clinical haematological relapse. Following DLI, five of these patients showed decreasing transcript levels from 2 to 5 logs between 4 and 12 months. In eight other patients studied long after BMT, five showed molecular relapse up to 117 months post-BMT and only one showed cytogenetic relapse. Our findings indicated that quantitative estimates of BCR-ABL transcripts were valuable for monitoring minimal residual disease in each patient.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics*
  • Bone Marrow Transplantation*
  • Child
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / biosynthesis
  • Fusion Proteins, bcr-abl / genetics*
  • Graft Enhancement, Immunologic
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy
  • Lymphocyte Transfusion*
  • Male
  • Middle Aged
  • Neoplasm, Residual
  • Polymerase Chain Reaction / methods*
  • Predictive Value of Tests
  • RNA, Messenger / analysis*
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / analysis*
  • RNA, Neoplasm / biosynthesis
  • Recurrence
  • Remission Induction
  • Sensitivity and Specificity
  • Transplantation, Homologous

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • RNA, Messenger
  • RNA, Neoplasm
  • Fusion Proteins, bcr-abl