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Outcome of patients with relapsed or refractory chronic lymphocytic leukemia treated with flavopiridol: impact of genetic features

Leukemia volume 26, pages 1442–1444 (2012)Cite this article

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Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is currently incurable outside of stem cell transplantation. Chromosomal abnormalities are common in CLL, with up to 80% of patients possessing abnormalities detected by fluorescence in situ hybridization (FISH) analysis.1 The acquisition of cytogenetic abnormalities is also common, and the presence of complex karyotype (⩾3 cytogenetic abnormalities) is associated with an adverse prognosis,2, 3, 4, 5 as are specific abnormalities. Deletion of 17p13.1, which results in loss of TP53, and 11q22.3, which results in loss of ATM, are found in 10% and 15–20% of patients, respectively. These are both associated with aggressive disease and shortened survival.1, 6, 7, 8, 9, 10 Thus, new therapies that are effective in patients with high-risk abnormalities represent a priority.

The cyclin-dependent kinase inhibitor flavopiridol has been shown to be effective in patients with relapsed and refractory CLL, including those refractory to fludarabine. In the initial phase I studies using an active dosing schedule of flavopiridol, approximately 40% of patients responded, including high response rates in patients with genetically high-risk disease.11 In a subsequent phase II trial, >50% of heavily pretreated patients responded.12 These two trials, OSU 0055 and OSU 0491, now have a longer follow-up (median 2.8 years), and herein we examine the contribution of interphase cytogenetic abnormalities and complex karyotype to response, progression-free survival (PFS) and overall survival (OS).

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Acknowledgements

This work was supported by Leukemia and Lymphoma Society SCOR Grant, the D. Warren Brown Foundation, NIH/NCI; P01 CA81534 and 5KL2RR025754-02, P50-CA140158, 5K12 CA133250-03, N01-CM-62207 and U01 CA 076576. AJ is a Paul Calabresi Scholar.

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Author notes

  1. J A Woyach and G Lozanski: These co-first authors contributed equally to this work.

  2. N A Heerema and J C Byrd: These co-senior authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

    J A Woyach, A S Ruppert, A Lozanski, K A Blum, J A Jones, J M Flynn, A J Johnson, M R Grever & J C Byrd

  2. Department of Pathology, The Ohio State University, Columbus, OH, USA

    G Lozanski

  3. Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA

    A J Johnson & J C Byrd

  4. Division of Cytogenetics, Department of Pathology, The Ohio State University, Columbus, OH, USA

    N A Heerema

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  1. J A Woyach
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  2. G Lozanski
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Correspondence to J A Woyach or J C Byrd.

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Competing interests

Dr Michael Grever and John Byrd have a use patent on flavopiridol that has not been awarded and currently lacks financial value.

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Supplementary Information accompanies the paper on the Leukemia website

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Woyach, J., Lozanski, G., Ruppert, A. et al. Outcome of patients with relapsed or refractory chronic lymphocytic leukemia treated with flavopiridol: impact of genetic features. Leukemia 26, 1442–1444 (2012). https://doi.org/10.1038/leu.2011.375

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