RESUMO
Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n=396). For all patients, median age at ASCT was 56 years (range, 26-71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS)were 63.5% [95 % CI, 58.768.6 %] and 79.5 % [95 % CI, 75.383.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0136 m). For patients transplanted upfront and in multivariate analysis, age (HR=2 [1.23.4], p=.01, and HR=2.3 [1.24.5], p=.01), disease status at time of ASCT (HR=1.7 [1.12.6], p=.01 and HR=1.8 [1.13.1], p=.03), and use of rituximab (HR=0.5 [0.30.8], p=.002 and HR=0.5 [0.30.9], p=.01) were statistically predictive for both PFS and OS. Also, first line treatment including anthracycline and high-dose cytarabine followed by ASCT conditioned with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can provide a high response rate but may not be sufficient to cure MCL even when ASCT is performed upfront, highlighting the need for innovative approaches before ASCT, aiming to increase complete response rate, and after ASCT, to maintain response.
Assuntos
Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/terapia , Transplante de Células-Tronco , Condicionamento Pré-Transplante , Adulto , Fatores Etários , Idoso , Antraciclinas/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Autoenxertos , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n = 396). For all patients, median age at ASCT was 56 years (range, 26-71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS) were 63.5 % [95 % CI, 58.7-68.6 %] and 79.5 % [95 % CI, 75.3-83.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0-136 m). For patients transplanted upfront and in multivariate analysis, age (HR = 2 [1.2-3.4], p = .01, and HR = 2.3 [1.2-4.5], p = .01), disease status at time of ASCT (HR = 1.7 [1.1-2.6], p = .01 and HR = 1.8 [1.1-3.1], p = .03), and use of rituximab (HR = 0.5 [0.3-0.8], p = .002 and HR = 0.5 [0.3-0.9], p = .01) were statistically predictive for both PFS and OS. Also, first line treatment including anthracycline and high-dose cytarabine followed by ASCT conditioned with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can provide a high response rate but may not be sufficient to cure MCL even when ASCT is performed upfront, highlighting the need for innovative approaches before ASCT, aiming to increase complete response rate, and after ASCT, to maintain response.
Assuntos
Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/terapia , Transplante de Células-Tronco , Condicionamento Pré-Transplante , Adulto , Fatores Etários , Idoso , Antraciclinas/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Autoenxertos , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Waldenström's macroglobulinemia is a rare B-cell malignancy defined by medullar infiltration by clonal lymphoplasmocytic cells and monoclonal IgM secretion. Treatment is reserved for symptomatic patients. The main first-line treatment strategies combine immunotherapy (principally the anti-CD20 monoclonal antibody rituximab) with chemotherapeutic agents, including alkylating agents, purine analogs and/or bortezomib. The overall response rate to these conventional treatments is between 70 and 90%, but a cure cannot be expected. For patients with relapsed or refractory disease, drugs that were not used for first-line treatment and other agents such as immunomodulators can be tried, but the response rate is generally lower and the responses are shorter lived. Recently, advances in our understanding of the biology of Waldenström's macroglobulinemia have led to the development of new drugs targeting hyperactive pathways. This review focuses on current treatment options and on new therapeutic developments.
Assuntos
Macroglobulinemia de Waldenstrom/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/uso terapêutico , Bortezomib , Comorbidade , Progressão da Doença , Everolimo , Previsões , Síndrome de Guillain-Barré/complicações , Transplante de Células-Tronco Hematopoéticas , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia , Incidência , Lenalidomida , Glicoproteína Associada a Mielina/imunologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirazinas/uso terapêutico , Rituximab , Terapia de Salvação , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Transplante Autólogo , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/epidemiologia , Macroglobulinemia de Waldenstrom/genética , Conduta ExpectanteRESUMO
Waldenstrom's macroglobulinemia is a rare chronic lymphoproliferative disorder. Treatment is usually based on nucleoside analogues, alkylators, bortezomib and monoclonal antibodies, alone or in combination. Fludarabine is a fluorinated purine analogue effective in chronic lymphoproliferative disorders. In Waldenstrom's macroglobulinemia, fludarabine was first studied in patients with relapsed or refractory disease after alkylator therapy, yielding an overall response rate of 30%. In the late 1990 s, fludarabine started to be used as a first-line treatment monotherapy yielding response rates between 36 and 94%. A recent Phase III trial showed that fludarabine monotherapy was more effective than chlorambucil in terms of progression-free survival, duration of response and overall survival. Fludarabine has also been studied in combination with rituximab and/or alkylating agents, leading to better-quality and longer lasting responses. Hematological toxicity is a major concern; however, restricting first-line use of fludarabine in patients who do not qualify for autologous stem cell transplantation, require rapid disease control or have factors of poor prognosis.
Assuntos
Antineoplásicos/uso terapêutico , Vidarabina/análogos & derivados , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Quimioterapia Combinada , Humanos , Leucemia Mieloide Aguda/etiologia , Síndromes Mielodisplásicas/etiologia , Rituximab , Vidarabina/efeitos adversos , Vidarabina/uso terapêutico , Macroglobulinemia de Waldenstrom/mortalidadeRESUMO
Waldenström macroglobulinemia is a rare chronic lymphoproliferative disorder. Treatments are currently reserved for symptomatic patients and usually consist of nucleoside analogues (NAs), alkylating agents, bortezomib, and monoclonal antibodies, alone or in combination. Fludarabine and 2-chlorodeoxyadenosine (2-CdA) have been studied in first-line treatment of Waldenström macroglobulinemia (WM) since the end of the 1990s. In monotherapy, response rates vary between 36% and 94%. In a phase III trial, fludarabine in monotherapy was more efficient than chlorambucil for progression-free survival (PFS) (37.8 vs. 27.1 months), duration of response (DOR) (38.5 vs. 21.3 months) and overall survival (OS) (median not reached vs. 69.8 months), but the overall response rate (ORR) was similar (45.6% and 35.9%). NAs have been studied in combination with rituximab and/or alkylating agents for increasing the quality and duration of the response. Hematologic toxicities are a major concern, limiting the indication for NAs in first-line treatment to patients who are not candidates for autologous stem cell transplantation, those in need of rapid control of the disease, or those with poor prognostic factors.