F Castagnetti1, G Gugliotta2, M Baccarani3, M Breccia4, G Specchia5, L Levato6, E Abruzzese7, G Rossi8, A Iurlo9, B Martino10, P Pregno11, F Stagno12, A Cuneo13, M Bonifacio14, M Gobbi15, D Russo16, A Gozzini17, M Tiribelli18, A de Vivo2, G Alimena4, M Cavo2, G Martinelli2, F Pane19, G Saglio20, G Rosti2. 1. Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', 'S. Orsola-Malpighi' University Hospital. Electronic address: fausto.castagnetti@unibo.it. 2. Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology 'L. and A. Seràgnoli', 'S. Orsola-Malpighi' University Hospital. 3. Department of Hematology and Oncology 'L. and A. Seràgnoli', University of Bologna, Bologna. 4. Hematology Section, Department of Biotechnologies and Cellular Hematology, 'La Sapienza' University, Rome. 5. Chair of Hematology, University of Bari, Bari. 6. Hematology Unit, 'Pugliese-Ciaccio' Hospital, Catanzaro. 7. Hematology Unit, 'S. Eugenio' Hospital, Rome. 8. Hematology Unit, Azienda Ospedaliera 'Spedali Civili', Brescia. 9. Oncohematology of the Elderly Unit, Division of Oncohematology, IRCCS Ca' Granda-Maggiore University Hospital, Milan. 10. Hematology Unit, Azienda Ospedaliera 'Bianchi-Melacrino-Morelli', Reggio Calabria. 11. Hematology Unit, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Turin. 12. Hematology Section, Department of Biomedical Sciences, University of Catania, Catania. 13. Chair of Hematology, Azienda Ospedaliero-Universitaria Arcispedale S. Anna, University of Ferrara, Ferrara. 14. Hematology Section, Department of Medicine, University of Verona, Verona. 15. Clinical Hematology Unit, IRCCS AOU San Martino-IST, Genoa. 16. Blood Diseases and Stem Cell Transplantation Unit, Azienda Ospedaliera 'Spedali Civili', University of Brescia, Brescia. 17. Hematology Unit, 'Careggi' University Hospital, Florence. 18. Hematology Unit, 'S. Maria Della Misericordia' University Hospital, Udine. 19. Hematology Section, Department of Biochemistry and Medical Biotechnologies, 'Federico II' University, Naples. 20. Department of Clinical and Biological Sciences, 'S. Luigi Gonzaga' University Hospital, University of Torino, Orbassano, Italy.
Abstract
BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052.
BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052.
Authors: Simone Claudiani; Jane F Apperley; Robert Peter Gale; Richard Clark; Richard Szydlo; Simona Deplano; Renuka Palanicawandar; Jamshid Khorashad; Letizia Foroni; Dragana Milojkovic Journal: Haematologica Date: 2017-05-11 Impact factor: 9.941
Authors: Tariq I Mughal; Jason Gotlib; Ruben Mesa; Steffen Koschmieder; H Jean Khoury; Jorge E Cortes; Tiziano Barbui; Rüdiger Hehlmann; Michael Mauro; Susanne Saussele; Jerald P Radich; Richard A Van Etten; Giuseppe Saglio; Srdnan Verstovek; Robert Peter Gale; Omar Abdel-Wahab Journal: Leuk Res Date: 2018-02-14 Impact factor: 3.156
Authors: M Pfirrmann; M Baccarani; S Saussele; J Guilhot; F Cervantes; G Ossenkoppele; V S Hoffmann; F Castagnetti; J Hasford; R Hehlmann; B Simonsson Journal: Leukemia Date: 2015-09-29 Impact factor: 11.528
Authors: Francis J Giles; Delphine Rea; Gianantonio Rosti; Nicholas C P Cross; Juan Luis Steegmann; Laimonas Griskevicius; Philipp le Coutre; Daniel Coriu; Ljubomir Petrov; Gert J Ossenkoppele; Francois-Xavier Mahon; Susanne Saussele; Andrzej Hellmann; Perttu Koskenvesa; Tim H Brümmendorf; Gunther Gastl; Fausto Castagnetti; Beatrice Vincenzi; Jens Haenig; Andreas Hochhaus Journal: J Cancer Res Clin Oncol Date: 2017-03-31 Impact factor: 4.553
Authors: Frédéric Millot; Joëlle Guilhot; Meinolf Suttorp; Adalet Meral Güneş; Petr Sedlacek; Eveline De Bont; Chi Kong Li; Krzysztof Kalwak; Birgitte Lausen; Srdjana Culic; Michael Dworzak; Emilia Kaiserova; Barbara De Moerloose; Farah Roula; Andrea Biondi; André Baruchel Journal: Haematologica Date: 2017-08-24 Impact factor: 9.941