BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML

Richard Press, Zac Love, Ashlie A. Tronnes, Rui Yang, Thuan Tran, Solange Mongoue-Tchokote, Motomi (Tomi) Mori, Michael J. Mauro, Michael W. Deininger, Brian Druker

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Although most patients with chronic myeloid leukemia (CML) treated with imatinib mesylate achieve a complete cytogenetic response (CCR), some patients will relapse. To determine the potential of real-time quantitative BCR-ABL reverse transcriptase-polymerase chain reaction (RT-PCR) to predict the duration of continued CCR, we monitored 85 patients treated with imatinib mesylate who achieved a CCR. With a median follow-up of 13 months after CCR (29 months after imatinib mesylate; median 6 RQ-PCR assays), 23 patients (27%) had disease progression (predominantly loss of CCR). Compared with the median baseline level of BCR-ABL mRNA, 42% of patients achieved at least a 2-log molecular response at the time of first reaching CCR. Failure to achieve a 2-log response at the time of CCR was an independent predictive marker of subsequent progression-free survival (hazard ratio = 5.8; 95% CI, 1.7-20; P = .005). After CCR, BCR-ABL mRNA levels progressively declined for at least the next 15 months, and 42 patients (49%) ultimately achieved at least a 3-log reduction in BCR-ABL mRNA. Patients failing to achieve this 3-log response, at any time during therapy, had significantly shorter progression-free survival (hazard ratio = 8.1; 95% CI, 3.1-22; P <.001). The achievement of either a 2-log molecular response at the time of CCR or a 3-log response anytime thereafter is a significant and independent prognostic marker of subsequent progression-free survival.

Original languageEnglish (US)
Pages (from-to)4250-4256
Number of pages7
JournalBlood
Volume107
Issue number11
DOIs
StatePublished - Jun 1 2006

Fingerprint

Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Messenger RNA
Hazards
Polymerase chain reaction
RNA-Directed DNA Polymerase
Disease-Free Survival
Assays
Imatinib Mesylate
Reverse Transcriptase Polymerase Chain Reaction
Disease Progression
Recurrence
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Hematology

Cite this

BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML. / Press, Richard; Love, Zac; Tronnes, Ashlie A.; Yang, Rui; Tran, Thuan; Mongoue-Tchokote, Solange; Mori, Motomi (Tomi); Mauro, Michael J.; Deininger, Michael W.; Druker, Brian.

In: Blood, Vol. 107, No. 11, 01.06.2006, p. 4250-4256.

Research output: Contribution to journalArticle

Press, Richard ; Love, Zac ; Tronnes, Ashlie A. ; Yang, Rui ; Tran, Thuan ; Mongoue-Tchokote, Solange ; Mori, Motomi (Tomi) ; Mauro, Michael J. ; Deininger, Michael W. ; Druker, Brian. / BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML. In: Blood. 2006 ; Vol. 107, No. 11. pp. 4250-4256.
@article{0158f62e32d94bbab57f62bd2edbc1a6,
title = "BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML",
abstract = "Although most patients with chronic myeloid leukemia (CML) treated with imatinib mesylate achieve a complete cytogenetic response (CCR), some patients will relapse. To determine the potential of real-time quantitative BCR-ABL reverse transcriptase-polymerase chain reaction (RT-PCR) to predict the duration of continued CCR, we monitored 85 patients treated with imatinib mesylate who achieved a CCR. With a median follow-up of 13 months after CCR (29 months after imatinib mesylate; median 6 RQ-PCR assays), 23 patients (27{\%}) had disease progression (predominantly loss of CCR). Compared with the median baseline level of BCR-ABL mRNA, 42{\%} of patients achieved at least a 2-log molecular response at the time of first reaching CCR. Failure to achieve a 2-log response at the time of CCR was an independent predictive marker of subsequent progression-free survival (hazard ratio = 5.8; 95{\%} CI, 1.7-20; P = .005). After CCR, BCR-ABL mRNA levels progressively declined for at least the next 15 months, and 42 patients (49{\%}) ultimately achieved at least a 3-log reduction in BCR-ABL mRNA. Patients failing to achieve this 3-log response, at any time during therapy, had significantly shorter progression-free survival (hazard ratio = 8.1; 95{\%} CI, 3.1-22; P <.001). The achievement of either a 2-log molecular response at the time of CCR or a 3-log response anytime thereafter is a significant and independent prognostic marker of subsequent progression-free survival.",
author = "Richard Press and Zac Love and Tronnes, {Ashlie A.} and Rui Yang and Thuan Tran and Solange Mongoue-Tchokote and Mori, {Motomi (Tomi)} and Mauro, {Michael J.} and Deininger, {Michael W.} and Brian Druker",
year = "2006",
month = "6",
day = "1",
doi = "10.1182/blood-2005-11-4406",
language = "English (US)",
volume = "107",
pages = "4250--4256",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "11",

}

TY - JOUR

T1 - BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML

AU - Press, Richard

AU - Love, Zac

AU - Tronnes, Ashlie A.

AU - Yang, Rui

AU - Tran, Thuan

AU - Mongoue-Tchokote, Solange

AU - Mori, Motomi (Tomi)

AU - Mauro, Michael J.

AU - Deininger, Michael W.

AU - Druker, Brian

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Although most patients with chronic myeloid leukemia (CML) treated with imatinib mesylate achieve a complete cytogenetic response (CCR), some patients will relapse. To determine the potential of real-time quantitative BCR-ABL reverse transcriptase-polymerase chain reaction (RT-PCR) to predict the duration of continued CCR, we monitored 85 patients treated with imatinib mesylate who achieved a CCR. With a median follow-up of 13 months after CCR (29 months after imatinib mesylate; median 6 RQ-PCR assays), 23 patients (27%) had disease progression (predominantly loss of CCR). Compared with the median baseline level of BCR-ABL mRNA, 42% of patients achieved at least a 2-log molecular response at the time of first reaching CCR. Failure to achieve a 2-log response at the time of CCR was an independent predictive marker of subsequent progression-free survival (hazard ratio = 5.8; 95% CI, 1.7-20; P = .005). After CCR, BCR-ABL mRNA levels progressively declined for at least the next 15 months, and 42 patients (49%) ultimately achieved at least a 3-log reduction in BCR-ABL mRNA. Patients failing to achieve this 3-log response, at any time during therapy, had significantly shorter progression-free survival (hazard ratio = 8.1; 95% CI, 3.1-22; P <.001). The achievement of either a 2-log molecular response at the time of CCR or a 3-log response anytime thereafter is a significant and independent prognostic marker of subsequent progression-free survival.

AB - Although most patients with chronic myeloid leukemia (CML) treated with imatinib mesylate achieve a complete cytogenetic response (CCR), some patients will relapse. To determine the potential of real-time quantitative BCR-ABL reverse transcriptase-polymerase chain reaction (RT-PCR) to predict the duration of continued CCR, we monitored 85 patients treated with imatinib mesylate who achieved a CCR. With a median follow-up of 13 months after CCR (29 months after imatinib mesylate; median 6 RQ-PCR assays), 23 patients (27%) had disease progression (predominantly loss of CCR). Compared with the median baseline level of BCR-ABL mRNA, 42% of patients achieved at least a 2-log molecular response at the time of first reaching CCR. Failure to achieve a 2-log response at the time of CCR was an independent predictive marker of subsequent progression-free survival (hazard ratio = 5.8; 95% CI, 1.7-20; P = .005). After CCR, BCR-ABL mRNA levels progressively declined for at least the next 15 months, and 42 patients (49%) ultimately achieved at least a 3-log reduction in BCR-ABL mRNA. Patients failing to achieve this 3-log response, at any time during therapy, had significantly shorter progression-free survival (hazard ratio = 8.1; 95% CI, 3.1-22; P <.001). The achievement of either a 2-log molecular response at the time of CCR or a 3-log response anytime thereafter is a significant and independent prognostic marker of subsequent progression-free survival.

UR - http://www.scopus.com/inward/record.url?scp=33744463354&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744463354&partnerID=8YFLogxK

U2 - 10.1182/blood-2005-11-4406

DO - 10.1182/blood-2005-11-4406

M3 - Article

C2 - 16467199

AN - SCOPUS:33744463354

VL - 107

SP - 4250

EP - 4256

JO - Blood

JF - Blood

SN - 0006-4971

IS - 11

ER -