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2.
Leuk Lymphoma ; 64(7): 1225-1233, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37132428

RESUMO

Readily accessible biomarkers for risk stratification in settings with limited resources are lacking. We evaluated the effect of high red distribution width-coefficient of variation (RDW-CV) values (>14%) on all-cause and lymphoma-specific mortality outcomes among 118 patients with peripheral T-cell lymphoma (PTCL) who received systemic treatment at two tertiary centers between 2010 and 2019. With a median follow-up of 45 months, patients with a high RDW-CV had a lower 4-year overall survival rate (34% vs. 45%, p = 0.015) and higher cumulative incidence of lymphoma mortality (54% vs. 34%, p = 0.007). RDW-CV >14% was associated with all-cause (adjusted Hazard Ratio [aHR] 1.98, 95% confidence interval [CI] 1.10-3.56) and lymphoma-specific mortality (aHR 2.64, 95% CI 1.32-5.29). In our study, RDW-CV emerges as an easily accessible and complementary prognostic biomarker for risk stratification among treated patients with de novo PTCL. Further research should validate the predictive role of RDW-CV in prospective cohorts.


Assuntos
Índices de Eritrócitos , Linfoma de Células T Periférico , Humanos , Prognóstico , Estudos Retrospectivos , Estudos Prospectivos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia
4.
Cancer Manag Res ; 14: 1075-1085, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300062

RESUMO

Purpose: The aim of this study is to evaluate the oncological care during the first state of national emergency due to the COVID-19 pandemic in several public cancer hospitals in Peru. Materials and Methods: A multicentric cross-sectional descriptive study was conducted by interviewing adult cancer patients diagnosed and treated between January 2019 and February 2020 from 18 hospitals. This study was carried out in September 2020, the last month of the first state of national emergency. Demographic and clinical characteristics were evaluated, including COVID-19 status and cancer treatment features. Results: A total of 1472 patients were included; the median age was 55 years (range 19-97). Most patients (85.8%, n = 1263) had solid neoplasia, 13.5% (n = 198) hematologic neoplasia, and 0.7% (n = 11) others. SARS-CoV-2 infection was confirmed in 8.6% (n = 126), 1.2% (n = 18) were probable, 1.6% (n = 24) suspected, and 88.6% (n = 1304) negative cases. Overall, 51.6% of patients (n = 759) had cancer treatment delays, 42.5% (n = 626) changed treatment delivery (endovenous to oral systemic therapy), and 12.6% (n = 185) of cases cancer therapy was discontinued. In total, 10.3% (n = 117) of patients whose disease was controlled or in remission, experienced progression of disease during the state of emergency. A total of 6.7% (n = 98) of patients died, of whom 73.5% (n = 72) died from disease progression; 18.4% (n = 18) from SARS-CoV-2 infection and 8.1% (n = 8) from undetermined causes. Patients with hematological malignancies [hazard ratio (HR): 5.11 (95% confidence interval (CI): 1.99-13.07)] and no response to therapy before the onset of the pandemic [5.01 (1.44-17.42)] had an increased risk of death among COVID-19 infected individuals, whereas advanced clinical stage [5.09 (2.37-10.95)] and discontinuation of treatment [3.66 (1.97-6.78)] were risk factors among non-COVID-19 patients. Conclusion: Our study suggests that the COVID-19 pandemic has an adverse impact on the outcomes of Peruvian cancer patients. In our cohort, cancer mortality was higher than COVID-19 disease mortality.

5.
Leuk Lymphoma ; 63(2): 315-325, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34585997

RESUMO

Adult T-cell leukemia/lymphoma (ATLL) is a largely incurable disease. Cutaneous involvement is common and could be first symptom of the disease. We analyzed 169 patients with ATLL of whom 63 had cutaneous involvement. Cutaneous involvement was found in 48, 27, 17, and 60% of acute, lymphomatous, chronic and smoldering ATLL cases, respectively. Eight cases had primary cutaneous tumoral variant. Erythroderma (24%) and plaques (22%) were the most frequent skin lesions. The presence of cutaneous involvement was associated with better overall survival compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82], p < 0.01; 1-year OS 53 vs. 27%, respectively, p = 0.012). Combination zidovudine and interferon-alpha (AZT-IFN) yielded high response rates (overall response, OR = 100%, n = 8; complete response 62.5%) compared to chemotherapy (OR = 33.3%, n = 12/36). In conclusion, cutaneous involvement was associated with better survival in Latin American patients with ATLL. AZT-IFN demonstrated encouraging responses in ATLL patients with cutaneous involvement.


Assuntos
Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Linfoma , Neoplasias Cutâneas , Adulto , Humanos , Interferon-alfa/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/patologia , Linfoma/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/tratamento farmacológico
6.
JCO Glob Oncol ; 7: 1151-1166, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34270330

RESUMO

PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking. PATIENTS AND METHODS: We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test. RESULTS: We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year survival rates of 8%, 22%, 40%, and 80%, respectively. First-line zidovudine (AZT)-interferon alfa (IFN) resulted in an overall response rate of 63% (complete response [CR] 24%) for acute. First-line chemotherapy yielded an overall response rate of 41% (CR 29%) for lymphomatous. CR rate was 42% for etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone versus 12% for cyclophosphamide, vincristine, doxorubicin, and prednisone-like regimen (P < .001). Progression-free survival at 1 year for acute type patients treated with AZT-IFN was 67%, whereas 2-year progression-free survival in lymphomatous type patients who achieved CR after chemotherapy was 77%. CONCLUSION: This study confirms Latin American ATLL presents at a younger age and has a high incidence of lymphomatous type, low incidence of indolent subtypes, and worse survival rates as compared with Japanese patients. In aggressive ATLL, chemotherapy remains the preferred choice for lymphomatous favoring etoposide-based regimen (etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone), whereas AZT-IFN remains a good first-line option for acute subtype.


Assuntos
Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Argentina , Chile , Colômbia , Humanos , América Latina/epidemiologia , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Pessoa de Meia-Idade , Peru/epidemiologia
7.
An. Fac. Med. (Perú) ; 82(2): 161-168, abr.-jun 2021. tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1339090

RESUMO

RESUMEN La pandemia por COVID-19 originado por el Coronavirus 2 causante de síndrome respiratorio agudo severo (SARS-CoV-2) es causante de una crisis de salud pública a nivel global. Muchos reportes indican resultados desalentadores en pacientes con cáncer respecto a la población general. Por ello, los expertos en el manejo de neoplasias oncohematológicas del Instituto Nacional de Enfermedades Neoplásicas, hospitales nacionales y una clínica privada de Lima Metropolitana han desarrollado recomendaciones obtenidas por consenso para continuar con el manejo de pacientes con neoplasias oncohematológicas en forma segura ante la coyuntura de pandemia.


ABSTRACT The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global public health crisis. Many reports indicate disappointing results in cancer patients compared to the general population. Therefore, experts in the management of oncohematological malignancies from the National Institute of Neoplastic Diseases, national hospitals and a private clinic in Metropolitan Lima have developed recommendations obtained by consensus to continue with the management of patients with oncohematological neoplasms safely in the face of the pandemic.

8.
Leuk Res ; 102: 106513, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33561632

RESUMO

Data on response and survival outcomes of Latin American patients with diffuse Large B- cell lymphoma (DLBCL) are limited. We describe the clinical, inflammatory and immunohistochemical features of a cohort of DLBCL Peruvian patients treated with chemoimmunotherapy between 2010 and 2015. Logistic models were fitted for complete response (CR), and Cox proportional-hazard regression for progression-free survival (PFS) and overall survival (OS). Seventy-three patients were included in this analysis, 41 % had high/high-intermediate IPI and 48 % had high/high-intermediate NCCN-IPI scores, 41 % had non-germinal center (NGC) profile and 36 % were double expressors. CR was attained in 63 % of patients, median PFS was 53 months and median OS was 80 months. Both IPI and NCCN-IPI scores were statistically associated with PFS and OS. Neutrophil/lymphocyte ratio (NLR) ≥4 was associated with lower odds of CR (OR 0.19, p = 0.007), worse PFS (HR 2.67, p = 0.02) and worse OS (HR 2.77, p = 0.02). NLR ≥ 4 remained significant after adjusting for the IPI score and had a trend towards significance when adjusted for the NCCN-IPI score. Albumin <3.5 g/dl was associated with worse OS when adjusted for the NCCN-IPI score (HR 2.96, p = 0.04). NGC profile and double expressors were not prognostic. Our study identified NLR ≥ 4 and albumin <3.5 g/dl as potential adverse factors in DLBCL patients and could add to the prognostic value of the IPI or the NCCN-IPI scores.


Assuntos
Biomarcadores Tumorais/análise , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/patologia , Resultado do Tratamento , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Estudos de Coortes , Ciclofosfamida , Doxorrubicina , Etoposídeo , Feminino , Humanos , Imuno-Histoquímica , Inflamação/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Peru , Prednisona , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Rituximab , Vincristina
9.
Rev. colomb. cancerol ; 24(supl.1): 192-226, oct.-dic. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1251509

RESUMO

Resumen En diciembre de 2019 se detectó por primera vez en China la existencia del SARS-CoV2, causante de la enfermedad COVID-19. El virus rápidamente se propagó por Europa y Asia, tardándose un par de meses antes de llegar a América Latina. Se ha demostrado que los pacientes que desarrollan una enfermedad severa y que tienen mayor riesgo de mortalidad por COVID-19 son aquellos con edades avanzadas y que presentan por lo menos una enfermedad crónica, incluyendo el cáncer. Debido a lo anterior, surgen muchas dudas en el grupo de profesionales encargados de brindar tratamiento a pacientes con cáncer durante la pandemia, pues se debe equilibrar el riesgo-beneficio de proveer tratamiento a pacientes que se encuentran de base con un riesgo incrementado para tener manifestaciones severas por COVID-19. En este consenso planteamos recomendaciones para los profesionales en hematología que brindan tratamiento a pacientes que padecen de algún tipo de linfoma, con el fin de aclarar el panorama clínico durante la pandemia.


Abstract The existence of SARS-CoV2, the cause of COVID 19 disease, was detected for the first time in China in December 2019. The virus quickly spread across Europe and Asia, taking a couple months to reach Latin America. It has been shown that elderly patients and those with chronic diseases, including cancer, have a higher risk of mortality from COVID-19. Consequently, many doubts arise in the group of health professionals responsible for treating patients with cancer during the pandemic, as they must balance the risk-benefit of delivering treatment to patients with an increased risk for severe manifestations resulting from COVID-19. In this consensus we propose recommendations for hematology professionals who provide treatment to patients suffering from some type of lymphoma, with the aim of clarifying the clinical picture during the pandemic.


Assuntos
Humanos , Síndrome Respiratória Aguda Grave , COVID-19 , Linfoma , Consenso , Pandemias
10.
Rev Peru Med Exp Salud Publica ; 37(1): 115-121, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32520173

RESUMO

Immunotherapy has meant a great scientific advance in the treatment of cancer in recent years, being considered as the therapeutic cornerstone of some neoplasms. However, in some types of cancer only a fraction of patients achieve benefit, posing the challenges and limitations that lead us to the need to understand the complexity of tumor biology, the microenvironment and the responsiveness of each agent. The results currently exceed what was achieved by conventional chemotherapy, although it is not yet possible to determine whether these responses are lasting or represent cure. In this review, a broad approach to immunotherapy in cancer is proposed, from the basics to its clinical application, a discovery that was awarded the Nobel Prize in Medicine in 2018.


La inmunoterapia ha significado un gran avance científico en el tratamiento del cáncer en los últimos años, siendo considerada como la piedra angular terapéutica de algunas neoplasias. Sin embargo, en algunos tipos de cáncer sólo una fracción de pacientes alcanza beneficio, planteando los desafíos y limi tantes que nos llevan a la necesidad de entender la complejidad de la biología tumoral, el microambiente tumoral y la capacidad de respuesta de cada agente. Los resultados superan actualmente lo alcanzado por la quimioterapia convencional, aunque aún no se puede precisar si estas respuestas son duraderas o representan curación. En la presente revisión, se propone un enfoque amplio sobre la inmunoterapia en cáncer, desde los conceptos básicos hasta su aplicación clínica, descubrimiento que fue galardonado con el Premio Nobel de Medicina en el 2018.


Assuntos
Imunoterapia , Neoplasias , Humanos , Neoplasias/terapia , Prêmio Nobel
11.
Clin Lymphoma Myeloma Leuk ; 20(10): 637-646, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32513598

RESUMO

INTRODUCTION: We aimed at investigating the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in 2 independent cohorts of Latin American patients with diffuse large B-cell lymphoma (DLBCL) treated with chemoimmunotherapy. PATIENTS AND METHODS: The learning cohort was composed of 274 patients and the validation cohort of 323 patients, for a total of 597 patients. An optimal NLR cutoff ≥ 4 was determined using receiver operating characteristic analysis. RESULTS: In multivariate models, NLR ≥ 4 was independently associated with lower odds for complete response to chemoimmunotherapy in the learning (odds ratio, 0.46; P = .006) and the validation cohort (odds ratio, 0.49; P = .01), and independently associated with worse survival in the learning (hazard ratio, 1.55; P = .04) and the validation cohort (hazard ratio, 1.80; P = .003). CONCLUSIONS: The adverse prognostic value of NLR ≥ 4 was independent of the International Prognostic Index and the National Comprehensive Cancer Network-International Prognostic Index score. Based on the results of this multi-institutional study, NLR ≥ 4 emerges as an adverse prognostic factor in Latin American patients with DLBCL treated with chemoimmunotherapy.


Assuntos
Linfócitos/metabolismo , Linfoma Difuso de Grandes Células B/sangue , Neutrófilos/metabolismo , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida
12.
Rev. peru. med. exp. salud publica ; 37(1): 115-121, ene.-mar. 2020. graf
Artigo em Espanhol | LILACS | ID: biblio-1101799

RESUMO

RESUMEN La inmunoterapia ha significado un gran avance científico en el tratamiento del cáncer en los últimos años, siendo considerada como la piedra angular terapéutica de algunas neoplasias. Sin embargo, en algunos tipos de cáncer sólo una fracción de pacientes alcanza beneficio, planteando los desafíos y limi tantes que nos llevan a la necesidad de entender la complejidad de la biología tumoral, el microambiente tumoral y la capacidad de respuesta de cada agente. Los resultados superan actualmente lo alcanzado por la quimioterapia convencional, aunque aún no se puede precisar si estas respuestas son duraderas o representan curación. En la presente revisión, se propone un enfoque amplio sobre la inmunoterapia en cáncer, desde los conceptos básicos hasta su aplicación clínica, descubrimiento que fue galardonado con el Premio Nobel de Medicina en el 2018.


ABSTRACT Immunotherapy has meant a great scientific advance in the treatment of cancer in recent years, being considered as the therapeutic cornerstone of some neoplasms. However, in some types of cancer only a fraction of patients achieve benefit, posing the challenges and limitations that lead us to the need to understand the complexity of tumor biology, the microenvironment and the responsiveness of each agent. The results currently exceed what was achieved by conventional chemotherapy, although it is not yet possible to determine whether these responses are lasting or represent cure. In this review, a broad approach to immunotherapy in cancer is proposed, from the basics to its clinical application, a discovery that was awarded the Nobel Prize in Medicine in 2018.


Assuntos
Humanos , Imunoterapia , Neoplasias , Neoplasias/terapia , Prêmio Nobel
13.
Am J Hematol ; 95(4): 435-445, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32072672

RESUMO

DISEASE OVERVIEW: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an entity included in the 2016 WHO classification of lymphoid neoplasms. EBV+ DLBCL, NOS, is an aggressive B-cell lymphoma associated with chronic EBV infection, and a poor prognosis with standard chemotherapeutic approaches. DIAGNOSIS: The diagnosis is made through a careful pathological evaluation. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The differential diagnosis includes plasmablastic lymphoma (PBL), DLBCL associated with chronic inflammation and primary effusion lymphoma (PEL), among others. RISK-STRATIFICATION: The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers. MANAGEMENT: Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.


Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Terapia Combinada , Diagnóstico Diferencial , Gerenciamento Clínico , Infecções por Vírus Epstein-Barr/diagnóstico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/virologia , Transtornos Linfoproliferativos/diagnóstico , Prognóstico , Inibidores de Proteassoma/uso terapêutico , Medição de Risco , Transdução de Sinais , Terapias em Estudo
14.
Rev Gastroenterol Peru ; 39(3): 276-279, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31688853

RESUMO

Duodenal type follicular lymphoma is a rare malignancy accounting for less than 4% of primary non-Hodgkin lymphomas of the gastrointestinal tract and it is a new entity that was recently described in the new update WHO 2016. Data regarding long-term outcome are currently lacking, and for that reason, a consensus on the management of this disease has not been established and treatment. We report a case of a 57-year-old female patient diagnosed with duodenal- type follicular lymphoma grade 3a who was treated with R-CHOP. The aim of this study is to add more data for a greater characterization of the entity and thus select the best management for each case.


Assuntos
Neoplasias Duodenais , Linfoma Folicular , Neoplasias Duodenais/classificação , Neoplasias Duodenais/tratamento farmacológico , Neoplasias Duodenais/patologia , Feminino , Humanos , Linfoma Folicular/classificação , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Pessoa de Meia-Idade
15.
Clin Lymphoma Myeloma Leuk ; 19(9): e551-e557, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31320254

RESUMO

INTRODUCTION: The red blood cell distribution width (RDW) is an easy-to-obtain laboratory value that has emerged as a potential prognostic factor in solid and hematologic malignancies. PATIENTS AND METHODS: We evaluated 121 patients with de novo diffuse large B-cell lymphoma (DLBCL) treated with standard chemoimmunotherapy at our institution between 2010 and 2012. We categorized patients with high RDW (> 14.6%) and normal RDW (11.6%-14.6%). We fitted multivariate regression models for complete response (CR) and overall survival (OS). RESULTS: Patients with high RDW were less likely to achieve CR to chemoimmunotherapy than patients with normal RDW (48% vs. 83%; P < .001). The 5-year OS rate for patients with high RDW was lower than in patients with normal RDW (51% vs. 79%; P = .001). In multivariate regression models, high RDW was independently associated with lower odds of achieving CR (odds ratio, 0.32; 95% confidence interval [CI], 0.12-0.83; P = .02) and with higher risk of death from any cause (hazard ratio [HR], 2.04; 95% CI, 1.03-4.02; P = .04) than normal RDW in patients with DLBCL treated with chemoimmunotherapy. High RDW remained an independent adverse factor for OS after adjustment for the International Prognostic Index and the National Comprehensive Cancer Network-International Prognostic Index scores with HR 2.20 (95% CI, 1.12-4.31; P = .02) and HR 2.67 (95% CI 1.28-5.59; P = .009), respectively. CONCLUSION: High RDW appears to be an adverse predictive and prognostic factor in patients with de novo DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).


Assuntos
Índices de Eritrócitos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/mortalidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêutico
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