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Arch Pathol Lab Med. 2014 Sep;138(9):1186-92. doi: 10.5858/arpa.2013-0584-OA. Epub 2013 Dec 5.

Correlations between cytogenetic and molecular monitoring among patients with newly diagnosed chronic myeloid leukemia in chronic phase: post hoc analyses of the Rationale and Insight for Gleevec High-Dose Therapy study.

Author information

1
From the Indiana Blood and Marrow Transplantation, Stem Cell Transplantation Program, St. Francis Hospital and Health Centers, Indianapolis, Indiana (Dr Akard); the Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston (Dr Cortes); the Departments of Oncology/Hematopathology and Research and Development, NeoGenomics Laboratories, Irvine, California (Dr Albitar); the Division of Leukemia, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey (Dr Goldberg); Biostatistics (Dr Warsi) and Oncology Clinical Development (Dr Ericson), Novartis Pharmaceuticals Corporation, East Hanover, New Jersey; the Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York (Dr Wetzler); and the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington (Dr Radich).

Abstract

CONTEXT:

Although bone marrow (BM) karyotyping has been the standard in monitoring patients with chronic myeloid leukemia, peripheral blood (PB) monitoring methods may be more convenient.

OBJECTIVE:

To conduct post hoc analyses of the Rationale and Insight for Gleevec High-Dose Therapy study to evaluate correlations between results of cytogenetic testing and molecular monitoring from BM and PB during the first 18 months of high-dose imatinib therapy, and between early and late molecular responses.

DESIGN:

Newly diagnosed patients with chronic-phase chronic myeloid leukemia received imatinib 400 mg twice daily and were monitored quarterly for up to 18 months. Cytogenetic testing was performed by karyotyping using BM or by fluorescence in situ hybridization using PB. Molecular testing was performed by quantitative reverse transcriptase polymerase chain reaction using BM and PB.

RESULTS:

Significant pairwise correlations were found between results obtained by karyotyping, fluorescence in situ hybridization, and quantitative reverse transcriptase polymerase chain reaction using PB or BM (all pairwise correlations >0.8; P < .001). At 12 months, cytogenetic response by karyotyping correlated well with response by fluorescence in situ hybridization. A median 2.579-log reduction in BCR-ABL1 level from a standardized baseline correlated with fluorescence in situ hybridization-negative status. Patients with greater than 2-log reduction in BCR-ABL1 level at 3, 6, and 9 months were more likely to achieve major molecular response at 18 months than those with 2-log reduction or less.

CONCLUSIONS:

Our findings support the feasibility of molecular monitoring using PB and suggest that molecular monitoring conducted at a single reliable reference laboratory can adequately track response without invasive BM testing. Our findings are consistent with other work indicating that early response to imatinib predicts favorable long-term outcome.

PMID:
24308645
DOI:
10.5858/arpa.2013-0584-OA
[Indexed for MEDLINE]

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