@article{d314cafdf0d44d0d8bf0a830bf882bed,
title = "Near-tetraploidy is associated with Richter transformation in chronic lymphocytic leukemia patients receiving ibrutinib",
abstract = "Ibrutinib is a highly effective targeted therapy for chronic lymphocytic leukemia (CLL). However, ibrutinib must be discontinued in a subset of patients due to progressive CLL or transformation to aggressive lymphoma (Richter transformation). Transformation occurs early in the course of therapy and has an extremely poor prognosis. Thus, identification of prognostic markers associated with transformation is of utmost importance. Near-tetraploidy (4 copies of most chromosomes within a cell) has been reported in various lymphomas, but its incidence and significance in CLL has not been described. Using fluorescence in situ hybridization, we detected near-tetraploidy in 9 of 297 patients with CLL prior to beginning ibrutinib treatment on 1 of 4 clinical trials (3.0%; 95% confidence interval [CI], 1.4%-5.7%). Near-tetraploidy was associated with aggressive disease characteristics: Rai stage 3/4 (P 5 .03), deletion 17p (P 5 .03), and complex karyotype (P 5 .01). Near-tetraploidy was also associated with ibrutinib discontinuation due to Richter transformation (P, .0001), but not due to progressive CLL (P 5 .41). Of the 9 patients with near-tetraploidy, 6 had Richter transformation with diffuse large B-cell lymphoma. In a multivariable model, near-tetraploidy (hazard ratio [HR], 8.66; 95% CI, 3.83-19.59; P, .0001) and complex karyotype (HR, 4.77; 95% CI, 1.42-15.94; P 5 .01) were independent risk factors for discontinuing ibrutinib due to transformation. Our results suggest that near-tetraploidy is a potential prognostic marker for Richter transformation to assess in patients going on ibrutinib.",
author = "Miller, {Cecelia R.} and Ruppert, {Amy S.} and Heerema, {Nyla A.} and Maddocks, {Kami J.} and Jadwiga Labanowska and Heather Breidenbach and Gerard Lozanski and Weiqiang Zhao and Gordon, {Amber L.} and Jones, {Jeffrey A.} and Flynn, {Joseph M.} and Jaglowski, {Samantha M.} and Andritsos, {Leslie A.} and Blum, {Kristie A.} and Awan, {Farrukh T.} and Rogers, {Kerry A.} and Grever, {Michael R.} and Johnson, {Amy J.} and Abruzzo, {Lynne V.} and Hertlein, {Erin K.} and Blachly, {James S.} and Woyach, {Jennifer A.} and Byrd, {John C.}",
note = "Funding Information: Oncology Young Investigator Award, an American Society of Hematology Scholar Award, the National Institutes of Health, National Institute of General Medical Sciences (T32 GM068412), and National Cancer Institute (R01 CA197870, R01 CA183444, R01 CA177292, K23 CA178183, P50 CA140158, P01 CA095426, R35 CA197734, and R01 CA182905). Clinical trials were funded all or in part by Pharmacyclics. Funding Information: NEAR-TETRAPLOIDY AND RICHTER TRANSFORMATION 1587 Oncology Young Investigator Award, an American Society of Hematology Scholar Award, the National Institutes of Health, National Institute of General Medical Sciences (T32 GM068412), and National Cancer Institute (R01 CA197870, R01 CA183444, R01 CA177292, K23 CA178183, P50 CA140158, P01 CA095426, R35 CA197734, and R01 CA182905). Clinical trials were funded all or in part by Pharmacyclics. Funding Information: Acknowledgments This work was supported by the D. Warren Brown Foundation, Michael and Judy Thomas, the Four Winds Foundation, The Leukemia & Lymphoma Society, an American Society of Clinical Publisher Copyright: {\textcopyright} 2017 by The American Society of Hematology",
year = "2017",
month = aug,
day = "22",
doi = "10.1182/bloodadvances.2017007302",
language = "English (US)",
volume = "1",
pages = "1584--1588",
journal = "Blood Advances",
issn = "2473-9529",
publisher = "American Society of Hematology",
number = "19",
}