Central nervous system involvement in CLL: an international retrospective study by ERIC, the European Research Initiative on CLL
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CHATZIKONSTANTINOU, Thomas; Mariia MIKHALEVA; Christian BRIEGHEL; Christina PAPANGELOU; Eva MINGA; Celso ARRAIS-RODRIGUES; Sotiria BESIKLI-DIMOU; Amalia CERUTTI; Michael DOUBEK; Lisbeth ENGGAARD; Blanca ESPINET; Blanca FERRER-LORES; Jose Antonio Garcia VELA; Massimo GENTILE; Eva Gimeno VAZQUEZ; Odit GUTWEIN; Yair HERISHANU; Paula JABLONOWSKA-BABIJ; Ozren JAKSIC; Par JOSEFSSON; Elzbieta KALICINSKA; Maria KISLOVA; Enrico LISTA; Ioannis KOTSIANIDIS; Juan MARQUET; Enrica Antonia MARTINO; Ciaran MCAULEY; Maria Jose Mela OSORIO; Riccardo MOIA; Claudia MOSQUERA; Eugene NIKITIN; Miguel Arturo PAVLOVSKY; Verena PFISTER; Emine Merve Savas COMMA; Lydia SCARFO; Matjaz SEVER; Lev SHVIDEL; Martin SIMKOVIC; Niki STAVROYIANNI; Persefoni TALIMTZI; Antigoni TRANIDOU; Andrea VISENTIN; Georgios VRACHIOLIAS; Ewa WASIK-SZCZEPANEK; Tomasz WROBEL; Munci YAGCI; Alessandro CELLINI; Anastasia CHATZIDIMITRIOU; Gianluca GAIDANO; Mary Ann ANDERSON; Matthew S DAVIDS; Jennifer R BROWN; Carsten U NIEMANN; Kostas STAMATOPOULOS; Paolo GHIA; Inhye E AHN a Maya KOREN-MICHOWITZ
Central nervous system involvement (CNSi) of chronic lymphocytic leukemia (CLL) is a rare condition with no consensus on diagnostic criteria and limited evidence for management and outcome. Here, we report an international, multicenter, retrospective study conducted by the European Research Initiative on CLL. The study defined CNSi of CLL by the following: (1) detection of CLL cells in the cerebrospinal fluid or confirmation of CLL infiltration of the CNS based on a tissue biopsy, (2) clinical or radiographic evidence of neurologic disease, and (3) the absence of other explanations for the neurologic findings. A total of 48 patients from 26 centers in 15 countries met all 3 diagnostic criteria of CLL-CNSi. Median age at diagnosis of CNSi was 64 years. Most patients were males (73%), had Binet stage A at CLL diagnosis (61%), and had untreated CLL at the time of CNSi (63%). Motor impairment was the most common symptom (38%) followed by visual impairment (32%). Of 47 patients who received treatment for CNSi, half (51%) received targeted agents, most often a Bruton tyrosine kinase inhibitor (BTKi), and 34% received chemoimmunotherapy. Initial treatment was highly effective, leading to a reduction (83%) or complete resolution (71%) of neurologic symptoms and imaging findings in most patients. The estimated 5-year overall survival (OS) from the CNSi diagnosis was 77.1%. The 5-year time to next treatment or death was 94% for patients treated with BTKi compared with 64% for those treated with CIT. Treatment-sensitive disease, represented by attainment of CNS complete response after initial therapy, was associated with longer OS.
CHATZIKONSTANTINOU, Thomas; Mariia MIKHALEVA; Christian BRIEGHEL; Christina PAPANGELOU; Eva MINGA; Celso ARRAIS-RODRIGUES; Sotiria BESIKLI-DIMOU; Amalia CERUTTI; Michael DOUBEK; Lisbeth ENGGAARD; Blanca ESPINET; Blanca FERRER-LORES; Jose Antonio Garcia VELA; Massimo GENTILE; Eva Gimeno VAZQUEZ; Odit GUTWEIN; Yair HERISHANU; Paula JABLONOWSKA-BABIJ; Ozren JAKSIC; Par JOSEFSSON; Elzbieta KALICINSKA; Maria KISLOVA; Enrico LISTA; Ioannis KOTSIANIDIS; Juan MARQUET; Enrica Antonia MARTINO; Ciaran MCAULEY; Maria Jose Mela OSORIO; Riccardo MOIA; Claudia MOSQUERA; Eugene NIKITIN; Miguel Arturo PAVLOVSKY; Verena PFISTER; Emine Merve Savas COMMA; Lydia SCARFO; Matjaz SEVER; Lev SHVIDEL; Martin SIMKOVIC; Niki STAVROYIANNI; Persefoni TALIMTZI; Antigoni TRANIDOU; Andrea VISENTIN; Georgios VRACHIOLIAS; Ewa WASIK-SZCZEPANEK; Tomasz WROBEL; Munci YAGCI; Alessandro CELLINI; Anastasia CHATZIDIMITRIOU; Gianluca GAIDANO; Mary Ann ANDERSON; Matthew S DAVIDS; Jennifer R BROWN; Carsten U NIEMANN; Kostas STAMATOPOULOS; Paolo GHIA; Inhye E AHN a Maya KOREN-MICHOWITZ. Central nervous system involvement in CLL: an international retrospective study by ERIC, the European Research Initiative on CLL. Blood advances. AMSTERDAM: ELSEVIER, 2026, roč. 10, č. 2, s. 428-438. ISSN 2473-9529. Dostupné z: https://doi.org/10.1182/bloodadvances.2025017755.
@article{2565450, author = {Chatzikonstantinou, Thomas and Mikhaleva, Mariia and Brieghel, Christian and Papangelou, Christina and Minga, Eva and ArraisandRodrigues, Celso and BesikliandDimou, Sotiria and Cerutti, Amalia and Doubek, Michael and Enggaard, Lisbeth and Espinet, Blanca and FerrerandLores, Blanca and Vela, Jose Antonio Garcia and Gentile, Massimo and Vazquez, Eva Gimeno and Gutwein, Odit and Herishanu, Yair and JablonowskaandBabij, Paula and Jaksic, Ozren and Josefsson, Par and Kalicinska, Elzbieta and Kislova, Maria and Lista, Enrico and Kotsianidis, Ioannis and Marquet, Juan and Martino, Enrica Antonia and McAuley, Ciaran and Osorio, Maria Jose Mela and Moia, Riccardo and Mosquera, Claudia and Nikitin, Eugene and Pavlovsky, Miguel Arturo and Pfister, Verena and Comma, Emine Merve Savas and Scarfo, Lydia and Sever, Matjaz and Shvidel, Lev and Simkovic, Martin and Stavroyianni, Niki and Talimtzi, Persefoni and Tranidou, Antigoni and Visentin, Andrea and Vrachiolias, Georgios and WasikandSzczepanek, Ewa and Wrobel, Tomasz and Yagci, Munci and Cellini, Alessandro and Chatzidimitriou, Anastasia and Gaidano, Gianluca and Anderson, Mary Ann and Davids, Matthew S and Brown, Jennifer R and Niemann, Carsten U and Stamatopoulos, Kostas and Ghia, Paolo and Ahn, Inhye E and KorenandMichowitz, Maya}, article_location = {AMSTERDAM}, article_number = {2}, doi = {https://doi.org/10.1182/bloodadvances.2025017755}, keywords = {chronic myeloid leukemia; treatment-free remission; nilotinib; imatinib; phase III trial}, language = {eng}, issn = {2473-9529}, journal = {Blood advances}, title = {Central nervous system involvement in CLL: an international retrospective study by ERIC, the European Research Initiative on CLL}, url = {https://ashpublications.org/bloodadvances/article/10/2/428/547926/Central-nervous-system-involvement-in-CLL-an}, volume = {10}, year = {2026} }
TY - JOUR ID - 2565450 AU - Chatzikonstantinou, Thomas - Mikhaleva, Mariia - Brieghel, Christian - Papangelou, Christina - Minga, Eva - Arrais-Rodrigues, Celso - Besikli-Dimou, Sotiria - Cerutti, Amalia - Doubek, Michael - Enggaard, Lisbeth - Espinet, Blanca - Ferrer-Lores, Blanca - Vela, Jose Antonio Garcia - Gentile, Massimo - Vazquez, Eva Gimeno - Gutwein, Odit - Herishanu, Yair - Jablonowska-Babij, Paula - Jaksic, Ozren - Josefsson, Par - Kalicinska, Elzbieta - Kislova, Maria - Lista, Enrico - Kotsianidis, Ioannis - Marquet, Juan - Martino, Enrica Antonia - McAuley, Ciaran - Osorio, Maria Jose Mela - Moia, Riccardo - Mosquera, Claudia - Nikitin, Eugene - Pavlovsky, Miguel Arturo - Pfister, Verena - Comma, Emine Merve Savas - Scarfo, Lydia - Sever, Matjaz - Shvidel, Lev - Simkovic, Martin - Stavroyianni, Niki - Talimtzi, Persefoni - Tranidou, Antigoni - Visentin, Andrea - Vrachiolias, Georgios - Wasik-Szczepanek, Ewa - Wrobel, Tomasz - Yagci, Munci - Cellini, Alessandro - Chatzidimitriou, Anastasia - Gaidano, Gianluca - Anderson, Mary Ann - Davids, Matthew S - Brown, Jennifer R - Niemann, Carsten U - Stamatopoulos, Kostas - Ghia, Paolo - Ahn, Inhye E - Koren-Michowitz, Maya PY - 2026 TI - Central nervous system involvement in CLL: an international retrospective study by ERIC, the European Research Initiative on CLL JF - Blood advances VL - 10 IS - 2 SP - 428-438 EP - 428-438 PB - ELSEVIER SN - 24739529 KW - chronic myeloid leukemia KW - treatment-free remission KW - nilotinib KW - imatinib KW - phase III trial UR - https://ashpublications.org/bloodadvances/article/10/2/428/547926/Central-nervous-system-involvement-in-CLL-an N2 - Central nervous system involvement (CNSi) of chronic lymphocytic leukemia (CLL) is a rare condition with no consensus on diagnostic criteria and limited evidence for management and outcome. Here, we report an international, multicenter, retrospective study conducted by the European Research Initiative on CLL. The study defined CNSi of CLL by the following: (1) detection of CLL cells in the cerebrospinal fluid or confirmation of CLL infiltration of the CNS based on a tissue biopsy, (2) clinical or radiographic evidence of neurologic disease, and (3) the absence of other explanations for the neurologic findings. A total of 48 patients from 26 centers in 15 countries met all 3 diagnostic criteria of CLL-CNSi. Median age at diagnosis of CNSi was 64 years. Most patients were males (73%), had Binet stage A at CLL diagnosis (61%), and had untreated CLL at the time of CNSi (63%). Motor impairment was the most common symptom (38%) followed by visual impairment (32%). Of 47 patients who received treatment for CNSi, half (51%) received targeted agents, most often a Bruton tyrosine kinase inhibitor (BTKi), and 34% received chemoimmunotherapy. Initial treatment was highly effective, leading to a reduction (83%) or complete resolution (71%) of neurologic symptoms and imaging findings in most patients. The estimated 5-year overall survival (OS) from the CNSi diagnosis was 77.1%. The 5-year time to next treatment or death was 94% for patients treated with BTKi compared with 64% for those treated with CIT. Treatment-sensitive disease, represented by attainment of CNS complete response after initial therapy, was associated with longer OS. ER -
CHATZIKONSTANTINOU, Thomas; Mariia MIKHALEVA; Christian BRIEGHEL; Christina PAPANGELOU; Eva MINGA; Celso ARRAIS-RODRIGUES; Sotiria BESIKLI-DIMOU; Amalia CERUTTI; Michael DOUBEK; Lisbeth ENGGAARD; Blanca ESPINET; Blanca FERRER-LORES; Jose Antonio Garcia VELA; Massimo GENTILE; Eva Gimeno VAZQUEZ; Odit GUTWEIN; Yair HERISHANU; Paula JABLONOWSKA-BABIJ; Ozren JAKSIC; Par JOSEFSSON; Elzbieta KALICINSKA; Maria KISLOVA; Enrico LISTA; Ioannis KOTSIANIDIS; Juan MARQUET; Enrica Antonia MARTINO; Ciaran MCAULEY; Maria Jose Mela OSORIO; Riccardo MOIA; Claudia MOSQUERA; Eugene NIKITIN; Miguel Arturo PAVLOVSKY; Verena PFISTER; Emine Merve Savas COMMA; Lydia SCARFO; Matjaz SEVER; Lev SHVIDEL; Martin SIMKOVIC; Niki STAVROYIANNI; Persefoni TALIMTZI; Antigoni TRANIDOU; Andrea VISENTIN; Georgios VRACHIOLIAS; Ewa WASIK-SZCZEPANEK; Tomasz WROBEL; Munci YAGCI; Alessandro CELLINI; Anastasia CHATZIDIMITRIOU; Gianluca GAIDANO; Mary Ann ANDERSON; Matthew S DAVIDS; Jennifer R BROWN; Carsten U NIEMANN; Kostas STAMATOPOULOS; Paolo GHIA; Inhye E AHN a Maya KOREN-MICHOWITZ. Central nervous system involvement in CLL: an international retrospective study by ERIC, the European Research Initiative on CLL. \textit{Blood advances}. AMSTERDAM: ELSEVIER, 2026, roč.~10, č.~2, s.~428-438. ISSN~2473-9529. Dostupné z: https://doi.org/10.1182/bloodadvances.2025017755.