The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in Philadelphia chromosome-negative cells

Michael W N Deininger, Jorge Cortes, Ron Paquette, Byung Park, Andreas Hochhaus, Michele Baccarani, Richard Stone, Thomas Fischer, Hagop Kantarjian, Dietger Niederwieser, Carlo Gambacorti-Passerini, Charlene So, Insa Gathmann, John M. Goldman, Douglas Smith, Brian Druker, François Guilhot

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Abstract

BACKGROUND. Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells. METHODS. The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-phase CML who were treated with imatinib mesylate after failure of interferon-α according to whether they attained a major cytogenetic response (MCR) (n = 324 patients), an MCR with CCA/Ph-negative status (n = 30 patients), or no MCR (n = 161 patients). RESULTS. CCA/Ph-negative status most frequently involved chromosomes Y, 8, and 7. No significant differences in pretherapeutic risk factors were detected between patients who attained an MCR with and without CCA/Ph-negative cells, except that exposure to alkylating agents was more frequent in patients with CCA/Ph-negative cells, and overall and progression-free survival were identical. With a median follow-up of 51 months, only 2 patients developed myelodysplastic syndromes (MDS). CONCLUSIONS. The overall prognosis for patients who had CML with CCA/Ph-negative status was good and was driven by the CML response to imatinib mesylate. Isolated CCA/Ph-negative cells in the absence of morphologic evidence of MDS do not justify a change in therapy.

Original languageEnglish (US)
Pages (from-to)1509-1519
Number of pages11
JournalCancer
Volume110
Issue number7
DOIs
StatePublished - Oct 1 2007

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Philadelphia Chromosome
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chromosome Aberrations
Cytogenetics
Myelodysplastic Syndromes
Disease-Free Survival
Leukemia, Myeloid, Chronic Phase
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 7
Alkylating Agents
Chi-Square Distribution
Acute Myeloid Leukemia
Interferons
Logistic Models
Regression Analysis

Keywords

  • BCR-ABL
  • Chronic myeloid leukemia
  • Cytogenetic abnormalities
  • Imatinib
  • Philadelphia chromosome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in Philadelphia chromosome-negative cells. / Deininger, Michael W N; Cortes, Jorge; Paquette, Ron; Park, Byung; Hochhaus, Andreas; Baccarani, Michele; Stone, Richard; Fischer, Thomas; Kantarjian, Hagop; Niederwieser, Dietger; Gambacorti-Passerini, Carlo; So, Charlene; Gathmann, Insa; Goldman, John M.; Smith, Douglas; Druker, Brian; Guilhot, François.

In: Cancer, Vol. 110, No. 7, 01.10.2007, p. 1509-1519.

Research output: Contribution to journalArticle

Deininger, MWN, Cortes, J, Paquette, R, Park, B, Hochhaus, A, Baccarani, M, Stone, R, Fischer, T, Kantarjian, H, Niederwieser, D, Gambacorti-Passerini, C, So, C, Gathmann, I, Goldman, JM, Smith, D, Druker, B & Guilhot, F 2007, 'The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in Philadelphia chromosome-negative cells', Cancer, vol. 110, no. 7, pp. 1509-1519. https://doi.org/10.1002/cncr.22936
Deininger, Michael W N ; Cortes, Jorge ; Paquette, Ron ; Park, Byung ; Hochhaus, Andreas ; Baccarani, Michele ; Stone, Richard ; Fischer, Thomas ; Kantarjian, Hagop ; Niederwieser, Dietger ; Gambacorti-Passerini, Carlo ; So, Charlene ; Gathmann, Insa ; Goldman, John M. ; Smith, Douglas ; Druker, Brian ; Guilhot, François. / The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in Philadelphia chromosome-negative cells. In: Cancer. 2007 ; Vol. 110, No. 7. pp. 1509-1519.
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abstract = "BACKGROUND. Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells. METHODS. The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-phase CML who were treated with imatinib mesylate after failure of interferon-α according to whether they attained a major cytogenetic response (MCR) (n = 324 patients), an MCR with CCA/Ph-negative status (n = 30 patients), or no MCR (n = 161 patients). RESULTS. CCA/Ph-negative status most frequently involved chromosomes Y, 8, and 7. No significant differences in pretherapeutic risk factors were detected between patients who attained an MCR with and without CCA/Ph-negative cells, except that exposure to alkylating agents was more frequent in patients with CCA/Ph-negative cells, and overall and progression-free survival were identical. With a median follow-up of 51 months, only 2 patients developed myelodysplastic syndromes (MDS). CONCLUSIONS. The overall prognosis for patients who had CML with CCA/Ph-negative status was good and was driven by the CML response to imatinib mesylate. Isolated CCA/Ph-negative cells in the absence of morphologic evidence of MDS do not justify a change in therapy.",
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T1 - The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in Philadelphia chromosome-negative cells

AU - Deininger, Michael W N

AU - Cortes, Jorge

AU - Paquette, Ron

AU - Park, Byung

AU - Hochhaus, Andreas

AU - Baccarani, Michele

AU - Stone, Richard

AU - Fischer, Thomas

AU - Kantarjian, Hagop

AU - Niederwieser, Dietger

AU - Gambacorti-Passerini, Carlo

AU - So, Charlene

AU - Gathmann, Insa

AU - Goldman, John M.

AU - Smith, Douglas

AU - Druker, Brian

AU - Guilhot, François

PY - 2007/10/1

Y1 - 2007/10/1

N2 - BACKGROUND. Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells. METHODS. The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-phase CML who were treated with imatinib mesylate after failure of interferon-α according to whether they attained a major cytogenetic response (MCR) (n = 324 patients), an MCR with CCA/Ph-negative status (n = 30 patients), or no MCR (n = 161 patients). RESULTS. CCA/Ph-negative status most frequently involved chromosomes Y, 8, and 7. No significant differences in pretherapeutic risk factors were detected between patients who attained an MCR with and without CCA/Ph-negative cells, except that exposure to alkylating agents was more frequent in patients with CCA/Ph-negative cells, and overall and progression-free survival were identical. With a median follow-up of 51 months, only 2 patients developed myelodysplastic syndromes (MDS). CONCLUSIONS. The overall prognosis for patients who had CML with CCA/Ph-negative status was good and was driven by the CML response to imatinib mesylate. Isolated CCA/Ph-negative cells in the absence of morphologic evidence of MDS do not justify a change in therapy.

AB - BACKGROUND. Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells. METHODS. The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-phase CML who were treated with imatinib mesylate after failure of interferon-α according to whether they attained a major cytogenetic response (MCR) (n = 324 patients), an MCR with CCA/Ph-negative status (n = 30 patients), or no MCR (n = 161 patients). RESULTS. CCA/Ph-negative status most frequently involved chromosomes Y, 8, and 7. No significant differences in pretherapeutic risk factors were detected between patients who attained an MCR with and without CCA/Ph-negative cells, except that exposure to alkylating agents was more frequent in patients with CCA/Ph-negative cells, and overall and progression-free survival were identical. With a median follow-up of 51 months, only 2 patients developed myelodysplastic syndromes (MDS). CONCLUSIONS. The overall prognosis for patients who had CML with CCA/Ph-negative status was good and was driven by the CML response to imatinib mesylate. Isolated CCA/Ph-negative cells in the absence of morphologic evidence of MDS do not justify a change in therapy.

KW - BCR-ABL

KW - Chronic myeloid leukemia

KW - Cytogenetic abnormalities

KW - Imatinib

KW - Philadelphia chromosome

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