CENTRAL NERVOUS SYSTEM INVOLVEMENT IN AGGRESSIVE ATLL: CAN WE PREDICT THE RISK IN A DEVASTATING COMPLICATION? EPIDEMIOLOGY AND CLINICAL FEATURES FROM LATIN AMERICA. A COLLABORATIVE STUDY FROM GRUPO DE ESTUDIO LATINO-AMERICANO DE LINFOPROLIFERATIVO (GELL) & T-CELL BRAZIL PROJECT (TCBP)
Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a mature, peripheral T-cell neoplasm caused by HTLV-1 and its lifetime risk is estimated as 4-7% among HTLV-1 carriers. Acute and lymphoma subtypes are highly aggressive diseases, characterized by shorter survival rates and a high risk of centra...
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2024-10-01
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| author | N Zing T Fischer E Miranda Y Gonzaga MA Dias RLR Baptista G Duffles R Schaffel FL Nogueira D Bortucchi RSA Silva SAB Brasil KZ Cecyn VLP Figueiredo NS Castro YS Rabelo GFS Barros A Hallack-Neto PPG Radtke MALHM Conhalato DV Clé J Pereira F Barroso RR Sousa H Quintero D Castro B Beltran D Enriquez J Vasquez C Roche D Artiles F Valvert L Villela C Oliver L Korin C Pena M Roa MAT Viera AV Glasenapp A Quiroz CS Figari R Rios S Paredes EE Saul C Bermack K Meza B Valcarcel CA Souza L Malpica CS Chiattone |
| author_facet | N Zing T Fischer E Miranda Y Gonzaga MA Dias RLR Baptista G Duffles R Schaffel FL Nogueira D Bortucchi RSA Silva SAB Brasil KZ Cecyn VLP Figueiredo NS Castro YS Rabelo GFS Barros A Hallack-Neto PPG Radtke MALHM Conhalato DV Clé J Pereira F Barroso RR Sousa H Quintero D Castro B Beltran D Enriquez J Vasquez C Roche D Artiles F Valvert L Villela C Oliver L Korin C Pena M Roa MAT Viera AV Glasenapp A Quiroz CS Figari R Rios S Paredes EE Saul C Bermack K Meza B Valcarcel CA Souza L Malpica CS Chiattone |
| author_sort | N Zing |
| collection | DOAJ |
| description | Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a mature, peripheral T-cell neoplasm caused by HTLV-1 and its lifetime risk is estimated as 4-7% among HTLV-1 carriers. Acute and lymphoma subtypes are highly aggressive diseases, characterized by shorter survival rates and a high risk of central nervous system involvement (iCNS) compared to other peripheral T-cell lymphomas. Currently, the treatment of ATLL remains a challenging. Our recent study on PTCL epidemiology and outcomes in Latin America (Thais et al. 2023 ASH Meeting) highlighted ATLL (18%) as the second most frequent subtype of PTCL, likely influenced by our distinct viral epidemiology. Objective: It is to assess the prevalence, clinical features, risk factors, and outcomes of iCNS in ATLL in Latin America. Methodology: Patients (pts) aged ≥18 years with newly diagnosed ATLL from GELL (n = 208, 2000-2023, retrospective) and TCBP (n = 83, 2015-2022, ambispective). Overall survival (OS) and progression free survival (PFS) were our endpoints. REDcap Platform (by Vanderbilt) was used to collect and store data, whereas for statistical analysis IBM-SPSS v.24. This trial is registered at Clinical trials (NCT03207789). Results: It was enrolled 291 pts, the prevalence of iCNS in ATLL was 7.9% (23/291), considering only aggressive forms (acute 40% and 60% lymphomatous). Pts'characteristics were similar between those without and with iCNS. There was a high frequency of advanced stage (90% vs 82%); ECOG ≥ 2 (45% vs 43%); B symptoms (74% vs 56%); elevated LDH (84% vs 78%); and IPI ≥3 (82% vs 65%) in the iCNS group. Treatment was heterogeneous including: IFN+AZT (74%) for acute subtypes, and CHOP (52%), CHOEP (26%) and EPOCH (2%), for lymphoma subtypes. Less than 30% of both groups achieved complete response at end of first treatment. Two clinical features were identified as possibly associated to iCNS: median age at diagnosis (55 [20-95] vs 44 [23-65]; p < 0.0001) and extra nodal involvement ≥ 2 (32% vs 65%, p = 0.005). The entire cohort of ATLL had 60- month OS and PFS of 16% [95% CI: 12-20%] and 9% [95% CI: 5-13%]; with median time of OS and PFS of 7 months (6-9) and 5 months (4-6). iCNS did not have an impact on survival outcomes (60 months OS 14% iCNS (n = 23) vs 16% no iCNS (n = 254), p = 0.91; PFS 12% vs 9% no iCNS, p = 0.61;) despite being a devastating complication. Outcomes in pts with lymphoma subtypes were slightly better than acute (60 months OS 19% vs 10%, p < 0.0001; PFS 12% vs 5%, p < 0.0001, respectively). Conclusion: Unlike other lymphoma subtypes, iCNS in ATLL does not appear to significantly impact outcomes. This paradoxical finding underscores the complexity of ATLL and may reflect the limitations of existing treatment options and the absence of standardized therapeutic protocols for this aggressive malignancy. The lack of significant survival difference, despite the severity of iCNS, points to an urgent need for innovative therapies and more effective treatment strategies. Our analysis identified median age at diagnosis and extranodal involvement as potential risk factors for iCNS, suggesting avenues for future prospective studies to further elucidate their role in disease progression. Given the high prevalence of ATLL in Latin America, there is a unique opportunity to advance our understanding of this disease through region-specific research. Collaborative efforts in this region could pave the way for breakthroughs in the management of ATLL and potentially offer insights applicable on a global scale. |
| format | Article |
| id | doaj-art-58c3427ca5c4476bba75d1029b8d3a5f |
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| language | English |
| publishDate | 2024-10-01 |
| publisher | Elsevier |
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| series | Hematology, Transfusion and Cell Therapy |
| spelling | doaj-art-58c3427ca5c4476bba75d1029b8d3a5f2025-08-20T02:17:40ZengElsevierHematology, Transfusion and Cell Therapy2531-13792024-10-0146S233S23410.1016/j.htct.2024.09.392CENTRAL NERVOUS SYSTEM INVOLVEMENT IN AGGRESSIVE ATLL: CAN WE PREDICT THE RISK IN A DEVASTATING COMPLICATION? EPIDEMIOLOGY AND CLINICAL FEATURES FROM LATIN AMERICA. A COLLABORATIVE STUDY FROM GRUPO DE ESTUDIO LATINO-AMERICANO DE LINFOPROLIFERATIVO (GELL) & T-CELL BRAZIL PROJECT (TCBP)N Zing0T Fischer1E Miranda2Y Gonzaga3MA Dias4RLR Baptista5G Duffles6R Schaffel7FL Nogueira8D Bortucchi9RSA Silva10SAB Brasil11KZ Cecyn12VLP Figueiredo13NS Castro14YS Rabelo15GFS Barros16A Hallack-Neto17PPG Radtke18MALHM Conhalato19DV Clé20J Pereira21F Barroso22RR Sousa23H Quintero24D Castro25B Beltran26D Enriquez27J Vasquez28C Roche29D Artiles30F Valvert31L Villela32C Oliver33L Korin34C Pena35M Roa36MAT Viera37AV Glasenapp38A Quiroz39CS Figari40R Rios41S Paredes42EE Saul43C Bermack44K Meza45B Valcarcel46CA Souza47L Malpica48CS Chiattone49Prevent Senior & A Beneficência Portuguesa de São Paulo (BP), São Paulo, BrazilAC Camargo Câncer Center, São Paulo, BrazilUniversidade Estadual de Campinas (UNICAMP), Campinas, BrazilInstituto Nacional de Câncer (INCA), Rio de Janeiro, BrazilUniversidade Federal da Bahia (UFBA), Salvador, BrazilUniversidade Estadual do Rio de Janeiro (UERJ) & Oncologia D'Or do Rio de Janeiro, Rio de Janeiro, BrazilUniversidade Estadual de Campinas (UNICAMP), Campinas, BrazilUniversidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilHospital Luxemburgo (HL), Belo Horizonte, BrazilFaculdade de Medicina do ABC (FMABC), Santo André, BrazilHemoMed, Instituto de Ensino e Pesquisa (IEP), São Paulo, BrazilIrmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, BrazilUniversidade Federal de São Paulo (UNIFESP), São Paulo, BrazilHospital do Servidor Público do Estado de São Paulo (HSPE), Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE), São Paulo, BrazilHospital de Amor de Barretos, Barretos, BrazilUniversidade Federal de Goiás (UFG), Goiânia, BrazilHospital Aldenora Bello, Sao Luís, BrazilUniversidade Federal de Juiz de Fora (UFJF), Juiz de Fora, BrazilHospital Santa Marcelina, São Paulo, BrazilSanta Casa de Belo Horizonte, Belo Horizonte, BrazilUniversidade de São Paulo (USP), Ribeirão Preto, BrazilUniversidade de São Paulo (USP), São Paulo, BrazilUniversidade Federal do Ceará (UFC), Fortaleza, BrazilUniversidade Federal do Ceará (UFC), Fortaleza, BrazilUniversidad del Valle del Cauca, Cali, ColombiaHospital Edgardo Rebagliati Martins, Lima, PeruHospital Edgardo Rebagliati Martins, Lima, PeruInstituto Nacional e Enfermedades Neoplasicas, Lima, PeruInstituto Nacional e Enfermedades Neoplasicas, Lima, PeruHospital Armando Milan Castro, Villa Clara, CubaHospital Armando Milan Castro, Villa Clara, CubaINCAN, Ciudad de Mexico, MexicoINCAN, Ciudad de Mexico, MexicoHospital Britanico de Montevideo, Montevideo, UruguayCABA-Alexander Fleming Institute, Olivos, ArgentinaHospital Del Salvador, Santiago, ChileHospital Del Salvador, Santiago, ChileClinica Santa Sofia, Caracas, VenezuelaHospital Central Instituto de Previsión Social, Asuncion, ParaguayHospital Central Instituto de Previsión Social, Asuncion, ParaguayOncosalud, AUNA, Lima, PeruHospital Clínico Quirúrgico Hermanos Amejeiras, La Habana, CubaHospital Edgardo Rebagliati Martins, Lima, PeruThe University of Texas, MD Anderson Cancer Center, Houston, United StatesThe University of Texas, MD Anderson Cancer Center, Houston, United StatesBaylor College of Medicine, Houston, United StatesGeorge Washington University, Washington, United StatesUniversidade Estadual de Campinas (UNICAMP), Campinas, BrazilThe University of Texas, MD Anderson Cancer Center, Houston, United StatesIrmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, Brazil; Hospital Samaritano, São Paulo, BrazilIntroduction: Adult T-cell leukemia/lymphoma (ATLL) is a mature, peripheral T-cell neoplasm caused by HTLV-1 and its lifetime risk is estimated as 4-7% among HTLV-1 carriers. Acute and lymphoma subtypes are highly aggressive diseases, characterized by shorter survival rates and a high risk of central nervous system involvement (iCNS) compared to other peripheral T-cell lymphomas. Currently, the treatment of ATLL remains a challenging. Our recent study on PTCL epidemiology and outcomes in Latin America (Thais et al. 2023 ASH Meeting) highlighted ATLL (18%) as the second most frequent subtype of PTCL, likely influenced by our distinct viral epidemiology. Objective: It is to assess the prevalence, clinical features, risk factors, and outcomes of iCNS in ATLL in Latin America. Methodology: Patients (pts) aged ≥18 years with newly diagnosed ATLL from GELL (n = 208, 2000-2023, retrospective) and TCBP (n = 83, 2015-2022, ambispective). Overall survival (OS) and progression free survival (PFS) were our endpoints. REDcap Platform (by Vanderbilt) was used to collect and store data, whereas for statistical analysis IBM-SPSS v.24. This trial is registered at Clinical trials (NCT03207789). Results: It was enrolled 291 pts, the prevalence of iCNS in ATLL was 7.9% (23/291), considering only aggressive forms (acute 40% and 60% lymphomatous). Pts'characteristics were similar between those without and with iCNS. There was a high frequency of advanced stage (90% vs 82%); ECOG ≥ 2 (45% vs 43%); B symptoms (74% vs 56%); elevated LDH (84% vs 78%); and IPI ≥3 (82% vs 65%) in the iCNS group. Treatment was heterogeneous including: IFN+AZT (74%) for acute subtypes, and CHOP (52%), CHOEP (26%) and EPOCH (2%), for lymphoma subtypes. Less than 30% of both groups achieved complete response at end of first treatment. Two clinical features were identified as possibly associated to iCNS: median age at diagnosis (55 [20-95] vs 44 [23-65]; p < 0.0001) and extra nodal involvement ≥ 2 (32% vs 65%, p = 0.005). The entire cohort of ATLL had 60- month OS and PFS of 16% [95% CI: 12-20%] and 9% [95% CI: 5-13%]; with median time of OS and PFS of 7 months (6-9) and 5 months (4-6). iCNS did not have an impact on survival outcomes (60 months OS 14% iCNS (n = 23) vs 16% no iCNS (n = 254), p = 0.91; PFS 12% vs 9% no iCNS, p = 0.61;) despite being a devastating complication. Outcomes in pts with lymphoma subtypes were slightly better than acute (60 months OS 19% vs 10%, p < 0.0001; PFS 12% vs 5%, p < 0.0001, respectively). Conclusion: Unlike other lymphoma subtypes, iCNS in ATLL does not appear to significantly impact outcomes. This paradoxical finding underscores the complexity of ATLL and may reflect the limitations of existing treatment options and the absence of standardized therapeutic protocols for this aggressive malignancy. The lack of significant survival difference, despite the severity of iCNS, points to an urgent need for innovative therapies and more effective treatment strategies. Our analysis identified median age at diagnosis and extranodal involvement as potential risk factors for iCNS, suggesting avenues for future prospective studies to further elucidate their role in disease progression. Given the high prevalence of ATLL in Latin America, there is a unique opportunity to advance our understanding of this disease through region-specific research. Collaborative efforts in this region could pave the way for breakthroughs in the management of ATLL and potentially offer insights applicable on a global scale.http://www.sciencedirect.com/science/article/pii/S2531137924007259 |
| spellingShingle | N Zing T Fischer E Miranda Y Gonzaga MA Dias RLR Baptista G Duffles R Schaffel FL Nogueira D Bortucchi RSA Silva SAB Brasil KZ Cecyn VLP Figueiredo NS Castro YS Rabelo GFS Barros A Hallack-Neto PPG Radtke MALHM Conhalato DV Clé J Pereira F Barroso RR Sousa H Quintero D Castro B Beltran D Enriquez J Vasquez C Roche D Artiles F Valvert L Villela C Oliver L Korin C Pena M Roa MAT Viera AV Glasenapp A Quiroz CS Figari R Rios S Paredes EE Saul C Bermack K Meza B Valcarcel CA Souza L Malpica CS Chiattone CENTRAL NERVOUS SYSTEM INVOLVEMENT IN AGGRESSIVE ATLL: CAN WE PREDICT THE RISK IN A DEVASTATING COMPLICATION? EPIDEMIOLOGY AND CLINICAL FEATURES FROM LATIN AMERICA. A COLLABORATIVE STUDY FROM GRUPO DE ESTUDIO LATINO-AMERICANO DE LINFOPROLIFERATIVO (GELL) & T-CELL BRAZIL PROJECT (TCBP) Hematology, Transfusion and Cell Therapy |
| title | CENTRAL NERVOUS SYSTEM INVOLVEMENT IN AGGRESSIVE ATLL: CAN WE PREDICT THE RISK IN A DEVASTATING COMPLICATION? EPIDEMIOLOGY AND CLINICAL FEATURES FROM LATIN AMERICA. A COLLABORATIVE STUDY FROM GRUPO DE ESTUDIO LATINO-AMERICANO DE LINFOPROLIFERATIVO (GELL) & T-CELL BRAZIL PROJECT (TCBP) |
| title_full | CENTRAL NERVOUS SYSTEM INVOLVEMENT IN AGGRESSIVE ATLL: CAN WE PREDICT THE RISK IN A DEVASTATING COMPLICATION? EPIDEMIOLOGY AND CLINICAL FEATURES FROM LATIN AMERICA. A COLLABORATIVE STUDY FROM GRUPO DE ESTUDIO LATINO-AMERICANO DE LINFOPROLIFERATIVO (GELL) & T-CELL BRAZIL PROJECT (TCBP) |
| title_fullStr | CENTRAL NERVOUS SYSTEM INVOLVEMENT IN AGGRESSIVE ATLL: CAN WE PREDICT THE RISK IN A DEVASTATING COMPLICATION? EPIDEMIOLOGY AND CLINICAL FEATURES FROM LATIN AMERICA. A COLLABORATIVE STUDY FROM GRUPO DE ESTUDIO LATINO-AMERICANO DE LINFOPROLIFERATIVO (GELL) & T-CELL BRAZIL PROJECT (TCBP) |
| title_full_unstemmed | CENTRAL NERVOUS SYSTEM INVOLVEMENT IN AGGRESSIVE ATLL: CAN WE PREDICT THE RISK IN A DEVASTATING COMPLICATION? EPIDEMIOLOGY AND CLINICAL FEATURES FROM LATIN AMERICA. A COLLABORATIVE STUDY FROM GRUPO DE ESTUDIO LATINO-AMERICANO DE LINFOPROLIFERATIVO (GELL) & T-CELL BRAZIL PROJECT (TCBP) |
| title_short | CENTRAL NERVOUS SYSTEM INVOLVEMENT IN AGGRESSIVE ATLL: CAN WE PREDICT THE RISK IN A DEVASTATING COMPLICATION? EPIDEMIOLOGY AND CLINICAL FEATURES FROM LATIN AMERICA. A COLLABORATIVE STUDY FROM GRUPO DE ESTUDIO LATINO-AMERICANO DE LINFOPROLIFERATIVO (GELL) & T-CELL BRAZIL PROJECT (TCBP) |
| title_sort | central nervous system involvement in aggressive atll can we predict the risk in a devastating complication epidemiology and clinical features from latin america a collaborative study from grupo de estudio latino americano de linfoproliferativo gell amp t cell brazil project tcbp |
| url | http://www.sciencedirect.com/science/article/pii/S2531137924007259 |
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avglasenapp centralnervoussysteminvolvementinaggressiveatllcanwepredicttheriskinadevastatingcomplicationepidemiologyandclinicalfeaturesfromlatinamericaacollaborativestudyfromgrupodeestudiolatinoamericanodelinfoproliferativogellamptcellbrazilprojecttcbp AT aquiroz centralnervoussysteminvolvementinaggressiveatllcanwepredicttheriskinadevastatingcomplicationepidemiologyandclinicalfeaturesfromlatinamericaacollaborativestudyfromgrupodeestudiolatinoamericanodelinfoproliferativogellamptcellbrazilprojecttcbp AT csfigari centralnervoussysteminvolvementinaggressiveatllcanwepredicttheriskinadevastatingcomplicationepidemiologyandclinicalfeaturesfromlatinamericaacollaborativestudyfromgrupodeestudiolatinoamericanodelinfoproliferativogellamptcellbrazilprojecttcbp AT rrios 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