Significance of increasing levels of minimal residual disease in patients with philadelphia chromosome-positive chronic myelogenous leukemia in complete cytogenetic response

Hagop M. Kantarjian, Jianqin Shan, Daniel Jones, Susan O'Brien, Mary Beth Rios, Elias Jabbour, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

Purpose: The aim of this study was to evaluate the clinical relevance of increases in quantitative polymerase chain reaction (QPCR) levels in patients with chronic myelogenous leukemia (CML) who are in complete cytogenetic response (CGCR) on therapy. Patients with Philadelphia chromosome (Ph)-positive CML receiving tyrosine kinase inhibitors (TKIs) are frequently monitored for response by QPCR studies for minimal molecular disease. The clinical significance of increasing levels of QPCR in patients in CGCR is uncertain. Patients and Methods: One hundred sixteen patients in durable CGCR, and on imatinib therapy for at least 18 months, had increases in QPCR levels (documented at least twice consecutively) as defined by literature reports. These were further analyzed by the achievement of major molecular response (MMR) defined as QPCR ≤ 0.05%, as well as by the degree of increase in QPCR. Results: Only 11 (9.5%) of 116 patients with increases in QPCR had CML progression; 10 of them were among 44 patients (23%) who either lost aMMRor never had a MMR, and had more than 1 log increase of QPCR. Conclusion: Most patients with increases in QPCR remain in CGCR. Patients who lose a MMR or never achieve a MMR, and have more than 1 log increase of QPCR, should be monitored more closely, and may be evaluated for mutations of BCR-ABL kinase domain and considered for investigational therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)3659-3663
Number of pages5
JournalJournal of Clinical Oncology
Volume27
Issue number22
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

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Philadelphia Chromosome
Residual Neoplasm
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Polymerase Chain Reaction
Protein-Tyrosine Kinases
Phosphotransferases
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Significance of increasing levels of minimal residual disease in patients with philadelphia chromosome-positive chronic myelogenous leukemia in complete cytogenetic response. / Kantarjian, Hagop M.; Shan, Jianqin; Jones, Daniel; O'Brien, Susan; Rios, Mary Beth; Jabbour, Elias; Cortes, Jorge.

In: Journal of Clinical Oncology, Vol. 27, No. 22, 01.08.2009, p. 3659-3663.

Research output: Contribution to journalArticle

Kantarjian, Hagop M. ; Shan, Jianqin ; Jones, Daniel ; O'Brien, Susan ; Rios, Mary Beth ; Jabbour, Elias ; Cortes, Jorge. / Significance of increasing levels of minimal residual disease in patients with philadelphia chromosome-positive chronic myelogenous leukemia in complete cytogenetic response. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 22. pp. 3659-3663.
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abstract = "Purpose: The aim of this study was to evaluate the clinical relevance of increases in quantitative polymerase chain reaction (QPCR) levels in patients with chronic myelogenous leukemia (CML) who are in complete cytogenetic response (CGCR) on therapy. Patients with Philadelphia chromosome (Ph)-positive CML receiving tyrosine kinase inhibitors (TKIs) are frequently monitored for response by QPCR studies for minimal molecular disease. The clinical significance of increasing levels of QPCR in patients in CGCR is uncertain. Patients and Methods: One hundred sixteen patients in durable CGCR, and on imatinib therapy for at least 18 months, had increases in QPCR levels (documented at least twice consecutively) as defined by literature reports. These were further analyzed by the achievement of major molecular response (MMR) defined as QPCR ≤ 0.05{\%}, as well as by the degree of increase in QPCR. Results: Only 11 (9.5{\%}) of 116 patients with increases in QPCR had CML progression; 10 of them were among 44 patients (23{\%}) who either lost aMMRor never had a MMR, and had more than 1 log increase of QPCR. Conclusion: Most patients with increases in QPCR remain in CGCR. Patients who lose a MMR or never achieve a MMR, and have more than 1 log increase of QPCR, should be monitored more closely, and may be evaluated for mutations of BCR-ABL kinase domain and considered for investigational therapeutic interventions.",
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