Paolo Strati1, Lynne V Abruzzo2, William G Wierda1, Susan O'Brien1, Alessandra Ferrajoli1, Michael J Keating3. 1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. 2. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX. 3. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: mkeating@mdanderson.org.
Abstract
BACKGROUND: Trisomy 12 (+12) is detected by fluorescence in-situ hybridization (FISH) analysis in up to 20% of patients with chronic lymphocytic leukemia (CLL). Patients with +12 are known to have unique features and to carry an intermediate prognosis. PATIENTS AND METHODS: In order to better define this large group, we reviewed the characteristics of 250 untreated patients with +12. RESULTS: When compared to 516 untreated patients negative for +12 by FISH, patients with +12 showed a higher incidence of thrombocytopenia, Richter transformation, and second malignant neoplasms (SMN), in addition to the expected increased rate of CD38 positivity and atypical immunophenotype. At a median follow-up of 51 months, 57% of patients needed first-line treatment; median time to first treatment was 38 months, and on multivariate analysis (MVA), it was found to be shorter in patients with advanced Rai stage, palpable splenomegaly, and deletion of 14q by conventional cytogenetic analysis. The overall response rate with first-line treatment was 94%. The median failure-free survival has not been reached, but on MVA, it was found to be shorter in patients whose disease responded in a manner other than complete remission or with FISH negativity for deletion 13q. The median overall survival for the entire group has not been reached, but MVA revealed it to be shorter in patients with an absolute lymphocyte count of > 30 × 10(9)/L or who developed SMN. Eighteen deaths have been observed so far, and Richter transformation and SMN were the leading causes of death (3 and 6, respectively). CONCLUSION: Patients with +12 CLL show characteristic clinical and biologic features, and may benefit from increased surveillance for second cancers.
BACKGROUND:Trisomy 12 (+12) is detected by fluorescence in-situ hybridization (FISH) analysis in up to 20% of patients with chronic lymphocytic leukemia (CLL). Patients with +12 are known to have unique features and to carry an intermediate prognosis. PATIENTS AND METHODS: In order to better define this large group, we reviewed the characteristics of 250 untreated patients with +12. RESULTS: When compared to 516 untreated patients negative for +12 by FISH, patients with +12 showed a higher incidence of thrombocytopenia, Richter transformation, and second malignant neoplasms (SMN), in addition to the expected increased rate of CD38 positivity and atypical immunophenotype. At a median follow-up of 51 months, 57% of patients needed first-line treatment; median time to first treatment was 38 months, and on multivariate analysis (MVA), it was found to be shorter in patients with advanced Rai stage, palpable splenomegaly, and deletion of 14q by conventional cytogenetic analysis. The overall response rate with first-line treatment was 94%. The median failure-free survival has not been reached, but on MVA, it was found to be shorter in patients whose disease responded in a manner other than complete remission or with FISH negativity for deletion 13q. The median overall survival for the entire group has not been reached, but MVA revealed it to be shorter in patients with an absolute lymphocyte count of > 30 × 10(9)/L or who developed SMN. Eighteen deaths have been observed so far, and Richter transformation and SMN were the leading causes of death (3 and 6, respectively). CONCLUSION:Patients with +12 CLL show characteristic clinical and biologic features, and may benefit from increased surveillance for second cancers.
Authors: Lorena Ripollés; Margarita Ortega; Francisco Ortuño; Ana González; Jesús Losada; Jesús Ojanguren; Joan Alfons Soler; Juan Bergua; Maria Dolors Coll; María Rosa Caballín Journal: Cancer Genet Cytogenet Date: 2006-11
Authors: Paolo Strati; Michael J Keating; Susan M O'Brien; Jan Burger; Alessandra Ferrajoli; Nitin Jain; Francesco Paolo Tambaro; Zeev Estrov; Jeffrey Jorgensen; Pramoda Challagundla; Stefan H Faderl; William G Wierda Journal: Blood Date: 2014-04-04 Impact factor: 22.113
Authors: Xose S Puente; Magda Pinyol; Víctor Quesada; Laura Conde; Gonzalo R Ordóñez; Neus Villamor; Georgia Escaramis; Pedro Jares; Sílvia Beà; Marcos González-Díaz; Laia Bassaganyas; Tycho Baumann; Manel Juan; Mónica López-Guerra; Dolors Colomer; José M C Tubío; Cristina López; Alba Navarro; Cristian Tornador; Marta Aymerich; María Rozman; Jesús M Hernández; Diana A Puente; José M P Freije; Gloria Velasco; Ana Gutiérrez-Fernández; Dolors Costa; Anna Carrió; Sara Guijarro; Anna Enjuanes; Lluís Hernández; Jordi Yagüe; Pilar Nicolás; Carlos M Romeo-Casabona; Heinz Himmelbauer; Ester Castillo; Juliane C Dohm; Silvia de Sanjosé; Miguel A Piris; Enrique de Alava; Jesús San Miguel; Romina Royo; Josep L Gelpí; David Torrents; Modesto Orozco; David G Pisano; Alfonso Valencia; Roderic Guigó; Mónica Bayés; Simon Heath; Marta Gut; Peter Klatt; John Marshall; Keiran Raine; Lucy A Stebbings; P Andrew Futreal; Michael R Stratton; Peter J Campbell; Ivo Gut; Armando López-Guillermo; Xavier Estivill; Emili Montserrat; Carlos López-Otín; Elías Campo Journal: Nature Date: 2011-06-05 Impact factor: 49.962
Authors: Benjamin M Solomon; Kari G Rabe; Susan L Slager; Jerry D Brewer; James R Cerhan; Tait D Shanafelt Journal: J Clin Oncol Date: 2013-01-22 Impact factor: 44.544
Authors: Pietro Bulian; Riccardo Bomben; Michele Dal Bo; Antonella Zucchetto; Francesca Maria Rossi; Massimo Degan; Federico Pozzo; Tamara Bittolo; Vanessa Bravin; Tiziana D'Agaro; Michaela Cerri; Annalisa Chiarenza; Kari G Chaffee; Adalgisa Condoluci; Giovanni D'Arena; Michele Spina; Francesco Zaja; Gabriele Pozzato; Francesco Di Raimondo; Davide Rossi; Giovanni Del Poeta; Gianluca Gaidano; Tait D Shanafelt; Valter Gattei Journal: Haematologica Date: 2017-07-27 Impact factor: 9.941
Authors: Paul J Hampel; Hua-Jay J Cherng; Timothy G Call; Wei Ding; Mahsa Khanlari; Ellen D McPhail; Roberto N Miranda; Pei Lin; Hussein A Tawbi; Alessandra Ferrajoli; William G Wierda; Nitin Jain; Sameer A Parikh Journal: Blood Adv Date: 2020-09-22
Authors: Paolo Strati; Sameer A Parikh; Kari G Chaffee; Sara J Achenbach; Susan L Slager; Timothy G Call; Wei Ding; Diane F Jelinek; Curtis A Hanson; Neil E Kay; Tait D Shanafelt Journal: Br J Haematol Date: 2017-04-07 Impact factor: 6.998
Authors: Lynne V Abruzzo; Carmen D Herling; George A Calin; Christopher Oakes; Lynn L Barron; Haley E Banks; Vikram Katju; Michael J Keating; Kevin R Coombes Journal: Haematologica Date: 2018-07-05 Impact factor: 9.941
Authors: Caitlin E Coombes; Zachary B Abrams; Suli Li; Lynne V Abruzzo; Kevin R Coombes Journal: J Am Med Inform Assoc Date: 2020-07-01 Impact factor: 4.497