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, B Douglas Smith, Brian J. Druker, François Guilhot

Research output: Contribution to journalArticle

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

Deininger, M. W. N., Cortes, J., Paquette, R., Park, B., Hochhaus, A., Baccarani, M., ... Guilhot, F. (2007). The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in Philadelphia chromosome-negative cells. Cancer, 110(7), 1509-1519. https://doi.org/10.1002/cncr.22936

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, B Douglas; Druker, Brian J.; 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, BD, Druker, BJ & 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, B Douglas ; Druker, Brian J. ; 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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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, B Douglas

AU - Druker, Brian J.

AU - Guilhot, François

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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.

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