Hematopathologic and cytogenetic findings in imatinib mesylate-treated chronic myelogenous leukemia patients

14 Months' experience

Rita Braziel, Teresa M. Launder, Brian Druker, Susan Olson, R. Ellen Magenis, Michael J. Mauro, Charles L. Sawyers, Ronald L. Paquette, Michael E. O'Dwyer

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Imatinib mesylate, an Abl kinase inhibitor, produces sustained complete hematologic responses (CHRs) in chronic myelogenous leukemia (CML) patients, but the sequence and timing of morphologic and cytogenetic changes in CML patients during prolonged imatinib mesylate treatment has not been described. In this report, we document sequential hematologic and bone marrow findings in 19 interferon-refractory/interferon-intolerant chronic phase CML patients on imatinib mesylate for at least 14 months. Patients treated at an effective oral dose (300 to 600 mg per day) were followed with peripheral blood (PB) counts, marrow examination, and cytogenetic studies at 0, 2, 5, 8, 11, and 14 months. By 2 months, 17 of 19 patients achieved CHR; 1 reached CHR by 5 months, and 1 at 11 months. Five of 19 patients developed cytopenias requiring treatment interruption and/or dose reduction, but all were able to continue in CHR on study. In contrast to interferonalfa treatment, imatinib mesylate-treated CML patients achieved not only CHR but complete morphologic marrow response. Normalization of marrow lagged behind PB response; however, by 8 months, all marrows showed normal or reduced cellularity without morphologic evidence of CML. Eighteen of 19 patients continued in CHR and morphologic marrow remission at 14 months; 1 patient relapsed with chronic phase CML. Although hematologic and marrow responses were uniform, cytogenetic responses were variable. Complete cytogenetic responses occurred in 6 patients, with 4 also in remission by fluorescent in situ hybridization and/or reverse-transcription-polymerase chain reaction. Six of 19 had partial and 7 of 19 no cytogenetic response. Several patients acquired additional clonal cytogenetic abnormalities during therapy, a finding with significant implications for prognosis and laboratory monitoring in imatinib mesylate-treated CML patients.

Original languageEnglish (US)
Pages (from-to)435-441
Number of pages7
JournalBlood
Volume100
Issue number2
DOIs
StatePublished - Jul 15 2002

Fingerprint

Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Bone Marrow
Interferons
Blood
Leukemia, Myeloid, Chronic Phase
Polymerase chain reaction
Transcription
Refractory materials
Bone
Phosphotransferases
Imatinib Mesylate
Monitoring
Therapeutics
Fluorescence In Situ Hybridization
Chromosome Aberrations
Reverse Transcription
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Hematology

Cite this

Hematopathologic and cytogenetic findings in imatinib mesylate-treated chronic myelogenous leukemia patients : 14 Months' experience. / Braziel, Rita; Launder, Teresa M.; Druker, Brian; Olson, Susan; Magenis, R. Ellen; Mauro, Michael J.; Sawyers, Charles L.; Paquette, Ronald L.; O'Dwyer, Michael E.

In: Blood, Vol. 100, No. 2, 15.07.2002, p. 435-441.

Research output: Contribution to journalArticle

Braziel, Rita ; Launder, Teresa M. ; Druker, Brian ; Olson, Susan ; Magenis, R. Ellen ; Mauro, Michael J. ; Sawyers, Charles L. ; Paquette, Ronald L. ; O'Dwyer, Michael E. / Hematopathologic and cytogenetic findings in imatinib mesylate-treated chronic myelogenous leukemia patients : 14 Months' experience. In: Blood. 2002 ; Vol. 100, No. 2. pp. 435-441.
@article{214def8a95f54147a6a362e890991427,
title = "Hematopathologic and cytogenetic findings in imatinib mesylate-treated chronic myelogenous leukemia patients: 14 Months' experience",
abstract = "Imatinib mesylate, an Abl kinase inhibitor, produces sustained complete hematologic responses (CHRs) in chronic myelogenous leukemia (CML) patients, but the sequence and timing of morphologic and cytogenetic changes in CML patients during prolonged imatinib mesylate treatment has not been described. In this report, we document sequential hematologic and bone marrow findings in 19 interferon-refractory/interferon-intolerant chronic phase CML patients on imatinib mesylate for at least 14 months. Patients treated at an effective oral dose (300 to 600 mg per day) were followed with peripheral blood (PB) counts, marrow examination, and cytogenetic studies at 0, 2, 5, 8, 11, and 14 months. By 2 months, 17 of 19 patients achieved CHR; 1 reached CHR by 5 months, and 1 at 11 months. Five of 19 patients developed cytopenias requiring treatment interruption and/or dose reduction, but all were able to continue in CHR on study. In contrast to interferonalfa treatment, imatinib mesylate-treated CML patients achieved not only CHR but complete morphologic marrow response. Normalization of marrow lagged behind PB response; however, by 8 months, all marrows showed normal or reduced cellularity without morphologic evidence of CML. Eighteen of 19 patients continued in CHR and morphologic marrow remission at 14 months; 1 patient relapsed with chronic phase CML. Although hematologic and marrow responses were uniform, cytogenetic responses were variable. Complete cytogenetic responses occurred in 6 patients, with 4 also in remission by fluorescent in situ hybridization and/or reverse-transcription-polymerase chain reaction. Six of 19 had partial and 7 of 19 no cytogenetic response. Several patients acquired additional clonal cytogenetic abnormalities during therapy, a finding with significant implications for prognosis and laboratory monitoring in imatinib mesylate-treated CML patients.",
author = "Rita Braziel and Launder, {Teresa M.} and Brian Druker and Susan Olson and Magenis, {R. Ellen} and Mauro, {Michael J.} and Sawyers, {Charles L.} and Paquette, {Ronald L.} and O'Dwyer, {Michael E.}",
year = "2002",
month = "7",
day = "15",
doi = "10.1182/blood.V100.2.435",
language = "English (US)",
volume = "100",
pages = "435--441",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - Hematopathologic and cytogenetic findings in imatinib mesylate-treated chronic myelogenous leukemia patients

T2 - 14 Months' experience

AU - Braziel, Rita

AU - Launder, Teresa M.

AU - Druker, Brian

AU - Olson, Susan

AU - Magenis, R. Ellen

AU - Mauro, Michael J.

AU - Sawyers, Charles L.

AU - Paquette, Ronald L.

AU - O'Dwyer, Michael E.

PY - 2002/7/15

Y1 - 2002/7/15

N2 - Imatinib mesylate, an Abl kinase inhibitor, produces sustained complete hematologic responses (CHRs) in chronic myelogenous leukemia (CML) patients, but the sequence and timing of morphologic and cytogenetic changes in CML patients during prolonged imatinib mesylate treatment has not been described. In this report, we document sequential hematologic and bone marrow findings in 19 interferon-refractory/interferon-intolerant chronic phase CML patients on imatinib mesylate for at least 14 months. Patients treated at an effective oral dose (300 to 600 mg per day) were followed with peripheral blood (PB) counts, marrow examination, and cytogenetic studies at 0, 2, 5, 8, 11, and 14 months. By 2 months, 17 of 19 patients achieved CHR; 1 reached CHR by 5 months, and 1 at 11 months. Five of 19 patients developed cytopenias requiring treatment interruption and/or dose reduction, but all were able to continue in CHR on study. In contrast to interferonalfa treatment, imatinib mesylate-treated CML patients achieved not only CHR but complete morphologic marrow response. Normalization of marrow lagged behind PB response; however, by 8 months, all marrows showed normal or reduced cellularity without morphologic evidence of CML. Eighteen of 19 patients continued in CHR and morphologic marrow remission at 14 months; 1 patient relapsed with chronic phase CML. Although hematologic and marrow responses were uniform, cytogenetic responses were variable. Complete cytogenetic responses occurred in 6 patients, with 4 also in remission by fluorescent in situ hybridization and/or reverse-transcription-polymerase chain reaction. Six of 19 had partial and 7 of 19 no cytogenetic response. Several patients acquired additional clonal cytogenetic abnormalities during therapy, a finding with significant implications for prognosis and laboratory monitoring in imatinib mesylate-treated CML patients.

AB - Imatinib mesylate, an Abl kinase inhibitor, produces sustained complete hematologic responses (CHRs) in chronic myelogenous leukemia (CML) patients, but the sequence and timing of morphologic and cytogenetic changes in CML patients during prolonged imatinib mesylate treatment has not been described. In this report, we document sequential hematologic and bone marrow findings in 19 interferon-refractory/interferon-intolerant chronic phase CML patients on imatinib mesylate for at least 14 months. Patients treated at an effective oral dose (300 to 600 mg per day) were followed with peripheral blood (PB) counts, marrow examination, and cytogenetic studies at 0, 2, 5, 8, 11, and 14 months. By 2 months, 17 of 19 patients achieved CHR; 1 reached CHR by 5 months, and 1 at 11 months. Five of 19 patients developed cytopenias requiring treatment interruption and/or dose reduction, but all were able to continue in CHR on study. In contrast to interferonalfa treatment, imatinib mesylate-treated CML patients achieved not only CHR but complete morphologic marrow response. Normalization of marrow lagged behind PB response; however, by 8 months, all marrows showed normal or reduced cellularity without morphologic evidence of CML. Eighteen of 19 patients continued in CHR and morphologic marrow remission at 14 months; 1 patient relapsed with chronic phase CML. Although hematologic and marrow responses were uniform, cytogenetic responses were variable. Complete cytogenetic responses occurred in 6 patients, with 4 also in remission by fluorescent in situ hybridization and/or reverse-transcription-polymerase chain reaction. Six of 19 had partial and 7 of 19 no cytogenetic response. Several patients acquired additional clonal cytogenetic abnormalities during therapy, a finding with significant implications for prognosis and laboratory monitoring in imatinib mesylate-treated CML patients.

UR - http://www.scopus.com/inward/record.url?scp=0037100308&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037100308&partnerID=8YFLogxK

U2 - 10.1182/blood.V100.2.435

DO - 10.1182/blood.V100.2.435

M3 - Article

VL - 100

SP - 435

EP - 441

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -