The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells |
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Authors: | 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 J Guilhot François |
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Affiliation: | Division of Hematology and Medical Oncology, Oregon Health & Science University Cancer Institute, Portland, Oregon 97239, USA. deininge@ohsu.edu |
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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-alpha 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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Keywords: | chronic myeloid leukemia cytogenetic abnormalities Philadelphia chromosome BCR‐ABL imatinib |
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