Prediction of response to imatinib by prospective quantitation of BCR-ABL transcript in late chronic phase chronic myeloid leukemia patients

G. Martinelli, I. Iacobucci, G. Rosti, F. Pane, M. Amabile, F. Castagnetti, D. Cilloni, S. Soverini, N. Testoni, G. Specchia, S. Merante, A. Zaccaria, F. Frassoni, G. Saglio, M. Baccarani

Research output: Contribution to journalArticle

Abstract

Imatinib mesylate (STI571), a specific Bcr-Abl inhibitor, has shown a potent antileukemic activity in clinical studies of chronic myeloid leukemia (CML) patients. Early prediction of response to imatinib cannot be anticipated. We used a standardized quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) for BCR-ABL transcripts on 191 out of 200 late-chronic phase CML patients enrolled in a phase II clinical trial with imatinib 400 mg/day. Bone marrow samples were collected before treatment, after 12, 20 and at the end of study treatment (52 weeks) while peripheral blood samples were obtained after 2, 3, 6, 10, 14, 20 and 52 weeks of therapy. The amount of BCR-ABL transcript was expressed as the ratio of BCR-ABL to β2-microglobulin (β2M). We show that, following initiation of imatinib, the early BCR-ABL level trends in both bone marrow and peripheral blood samples made it possible to predict the subsequent cytogenetic outcome and response. We propose this method as the method of choice for monitoring patients on imatinib therapy. QRT-PCR studies may be able to identify degrees of molecular response that predict both complete cytogenetic response and long term stability, as well as patterns of response that provide an early indication of relapse and imatinib resistance.

Original languageEnglish
Pages (from-to)495-502
Number of pages8
JournalAnnals of Oncology
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 2006

Keywords

  • Chronic myeloid leukemia
  • Imatinib mesylate
  • Late-chronic phase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Martinelli, G., Iacobucci, I., Rosti, G., Pane, F., Amabile, M., Castagnetti, F., Cilloni, D., Soverini, S., Testoni, N., Specchia, G., Merante, S., Zaccaria, A., Frassoni, F., Saglio, G., & Baccarani, M. (2006). Prediction of response to imatinib by prospective quantitation of BCR-ABL transcript in late chronic phase chronic myeloid leukemia patients. Annals of Oncology, 17(3), 495-502. https://doi.org/10.1093/annonc/mdj106