ABSTRACT
OBJECTIVE: Follicular and mantle cell lymphoma are low-grade B-cell malignancies that lack good responses to chemoimmunotherapy. This study aimed to assess retrospectively clinicopathological features and to determine independent prognostic factors for follicular and mantle cell lymphoma patients treated at two Brazilian medical centers: the Hematology and Hemotherapy Center of the Universidade Estadual de Campinas (Unicamp), a public university hospital, and AC. Camargo Cancer Center, a specialized cancer center. METHODS: Two hundred and twenty-seven follicular and 112 mantle cell lymphoma cases were diagnosed between 1999 and 2016. Archived paraffin blocks were retrieved and reviewed. Corresponding demographics and clinical data were recovered from medical charts. Outcome analyses considered both overall and event-free survival. RESULTS: For follicular lymphoma treated with the R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) and R-CVP (rituximab, cyclophosphamide, vincristine sulfate, prednisone) regimens, both B-symptoms (p-value < 0.01 for overall and event-free survival) and high-risk Follicular Lymphoma International Prognostic Index (p-value < 0.01 for overall survival) were independently associated to worse prognosis. Maintenance with rituximab improved the prognosis (p-value < 0.01 for overall survival). For mantle cell lymphoma, B-symptoms (p-value = 0.03 for overall survival and event-free survival) and bone marrow infiltration (p-value = 0.01 for overall survival) independently predicted reduced survival, and rituximab at induction increased both event-free and overall survival (p-value < 0.01 in both analyses). Combinations of these deleterious features could identify extremely poor prognostic subgroups. The administration of rituximab was more frequent in the AC. Camargo Cancer Center, which was the institution associated with better overall survival for both neoplasias. CONCLUSION: This study represents the largest cohort of follicular and mantle cell lymphoma in South America thus far. Some easily assessable clinical variables were able to predict prognosis and should be considered in low-income centers. In addition, the underuse of rituximab in the Brazilian public health system should be reconsidered in future health policies.
ABSTRACT
ABSTRACT Objective: Follicular and mantle cell lymphoma are low-grade B-cell malignancies that lack good responses to chemoimmunotherapy. This study aimed to assess retrospectively clinicopathological features and to determine independent prognostic factors for follicular and mantle cell lymphoma patients treated at two Brazilian medical centers: the Hematology and Hemotherapy Center of the Universidade Estadual de Campinas (Unicamp), a public university hospital, and AC. Camargo Cancer Center, a specialized cancer center. Methods: Two hundred and twenty-seven follicular and 112 mantle cell lymphoma cases were diagnosed between 1999 and 2016. Archived paraffin blocks were retrieved and reviewed. Corresponding demographics and clinical data were recovered from medical charts. Outcome analyses considered both overall and event-free survival. Results: For follicular lymphoma treated with the R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) and R-CVP (rituximab, cyclophosphamide, vincristine sulfate, prednisone) regimens, both B-symptoms (p-value < 0.01 for overall and event-free survival) and high-risk Follicular Lymphoma International Prognostic Index (p-value < 0.01 for overall survival) were independently associated to worse prognosis. Maintenance with rituximab improved the prognosis (p-value < 0.01 for overall survival). For mantle cell lymphoma, B-symptoms (p-value = 0.03 for overall survival and event-free survival) and bone marrow infiltration (p-value = 0.01 for overall survival) independently predicted reduced survival, and rituximab at induction increased both event-free and overall survival (p-value < 0.01 in both analyses). Combinations of these deleterious features could identify extremely poor prognostic subgroups. The administration of rituximab was more frequent in the AC. Camargo Cancer Center, which was the institution associated with better overall survival for both neoplasias. Conclusion: This study represents the largest cohort of follicular and mantle cell lymphoma in South America thus far. Some easily assessable clinical variables were able to predict prognosis and should be considered in low-income centers. In addition, the underuse of rituximab in the Brazilian public health system should be reconsidered in future health policies.
Subject(s)
Humans , Prognosis , Lymphoma, Follicular , Lymphoma, Mantle-CellABSTRACT
O linfoma folicular (LF) é um dos tipos mais frequentes de linfomas não-Hodgkin, correspondendo a cerca de 35% destes. O prognóstico destas neoplasias baseia-se em parâmetros clínicos e laboratoriais, que resultam em um índice utilizado internacionalmente, de aplicação relativamente fácil, o FLIPI (abreviatura do inglês, Follicular Lymphoma International Prognostic Índex). O objetivo deste estudo retrospectivo foi determinar o valor prognóstico da imunoexpressão de marcadores de proliferação celular: Ki-67 e Top-2a. Os prontuários de 170 pacientes foram revistos para obtenção dos dados clínicos e laboratoriais. Os preparados histológicos foram revistos e graduados em baixo grau (graus 1 ou 2 da OMS) e alto grau (grau 3a ou 3b). Posteriormente, foram submetidos à construção de um microarranjo de tecidos (tissue microarray) e à imunoistoquímica. A avaliação da imunoexpressão desses marcadores foi quantitativa [número de células positivas por µm2]. Os dados obtidos pela quantificação imunoistoquímica dos marcadores de proliferação celular foram relacionados com o grau histológico atribuído classicamente, com o FLIPI, a sobrevida global, sobrevida livre de doença e o risco de transformação para linfoma agressivo. Foi observado que os pacientes com Ki-67> ou = a 7 apresentaram menor sobrevida comparados aos que apresentaram Ki-67<7. Obtivemos também correlação positiva fraca entre Ki-67 e Top-2a. A Top-2a não demonstrou relação com a sobrevida global e a sobrevida livre da doença. Conclui-se que apenas a Ki-67 pode ser um promissor fator prognóstico para LF estabelecida atraves da sua relação com a sobrevida (AU)
Follicular lymphoma (FL) is one of the most common types of non-Hodgkin's lymphoma, accounting about 35%. The prognosis of these neoplasms are based in clinical and laboratory parameters, which result in an internationally index used, relatively easy to use, FLIPI (Follicular Lymphoma International Prognostic Index). The aim of this retrospective study is to determine the prognosis value of immunoexpression of cell proliferation markers: Ki-67 and Top-2a. Patient records of 170 patients were reviewed for clinical and laboratory data. Histological preparations were reviewed and graded in low grade (WHO grade 1 or 2) and high grade (grade 3a or 3b). Subsequently, they were submitted for the construction of a tissue microarray and immunohistochemistry. The immunoexpression evaluation of these markers was quantitative [number of positive cells per µm2]. The data obtained by the immunohistochemical quantification of the cell proliferation markers were related to the histological grade classically attributed to FLIPI, overall survival, disease-free survival rate and the risk of transformation to aggressive lymphoma. It was observed that patients with Ki-67> or = 7 showed lower survival compared to those with Ki-67 <7. We also obtained a weak positive correlation between Ki-67 and Top-2a. Top-2a no showed relation to overall survival rate and disease free survival rate. It is concluded that only Ki-67 may be a promising prognostic factor for FL established through its relation with survival rate (AU)