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 J. Druker, François Guilhot

Research output: Contribution to journalArticle

96 Scopus citations

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
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Deininger, M. W. N., 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, J. M., Smith, D., Druker, B. J., & 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