Observational Study of prognosis and therapeutics of Diffuse Large B Cell Lymphoma patients with high intermediate to high aIPI risk

Pacientes com linfoma difuso de grande célula B (LDGCB) do mesmo grupo de risco pelos critérios do Índice de Prognóstico Internacional (IPI), tratados com quimioterapia convencional à base de antraciclina, podem ter resposta terapêutica não esperada para seu grupo de risco. Isso pode ser explicado pelo fato do prognóstico dos LDGCB, que têm origem no centro germinativo (CG), ser superior aos originados após o CG (NCG). No intuito de aprimorar a avaliação de prognóstico e a abordagem terapêutica em LDGCB de IPI ajustado para a idade (IPIa) de risco intermediário alto e alto, elaboramos projeto de pesquisa, para verificar o papel dos marcadores imuno-histoquímicos (IH) e do transplante de medula óssea autólogo (ATMO), em primeira remissão completa (RC), neste grupo de pacientes. Avaliamos o impacto da expressão dos marcadores CD10, Bcl-6, MUM-1, Bcl-2 e p63 na obtenção de RC, sobrevida livre de doença (SLD) e sobrevida global (SG), isoladamente e de acordo com a origem em CG e NCG. Avaliamos 82 pacientes abaixo dos 60 anos, dos quais 16 (19,5%) receberam ATMO em primeira RC, além de serem comparados com os pacientes tratados com quimioterapia convencional e mantidos em observação após RC. A IH foi avaliável em 73 casos, 24 (32,9%) tiveram origem no CG e 49 (67,1%) NCG, sem diferença de sobrevida entre os grupos. A proteína Bcl-2 foi positiva em 27 (37%) pacientes e foi o único fator preditivo independente para SG à análise multivariada, com tendência de significância para RC. As SG e SLD em cinco anos para os 16 pacientes que receberam ATMO foi de 75% e 85,2%, respectivamente, a taxa de recidiva de 6,5% e diferença estatisticamente significativa para SLD (p = 0,015) em comparação aos pacientes apenas observados. Concluímos que o ATMO foi seguro e capaz de melhorar a sobrevida em LDGCB de risco intermediário alto e alto, e que a expressão de Bcl-2 pode ser utilizada na programação terapêutica inicial desses pacientes.Diffuse large B cell lymphoma (DLBCL) patients from the same risk group according to the International Prognostic Index (IPI) treated with conventional anthracycline-based chemotherapy may show an unexpected therapeutic response. This can be explained by the fact that the prognosis of DLBCL originating in germinal center (GC) cells is superior than that originating out of germinal center (NGC). In order to improve the prognostic evaluation and the therapeutic approach to DLBCL patients with high intermediate to high age-adjusted IPI (aIPI), a research project was designed for the analysis of immunohistochemical markers and the role of autologous stem cell transplantation (ASCT) in first complete remission (CR) for this group of patients. The impact of the expression of CD10, Bcl-6, MUM-1, Bcl-2 and p63 markers on complete remission (CR), disease-free survival (DFS) and overall survival (OS), either individually and according to cell origin was evaluated by means of immunohistochemistry. Eighty-two patients aged under 60 years old were assessed, of which 16 (19.5%) underwent ASCT in first CR and were compared to patients receiving conventional chemotherapy and being monitored after CR. Immunohistochemistry was assessable in 73 cases, 24 (32.9%) being classified as GC-type and 49 (67.1%) as NGC-type, with no survival difference between the two groups. Bcl-2 expression was found in 37% (27) of the patients and was the single independent predicting factor of OS prognosis according to multivariate analysis. A significant tendency of expression of this protein was also observed for achieving CR, which was essential for longer survival, as shown by multivariate analysis. OS and DFS within 5 years were of 75% and 85.2% respectively for the group of 16 patients treated with ASCT, which resulted in lower relapse rates (6.5%) with statistically significant difference for DFS (p=0.015) when compared to the group of patients who achieved CR and was kept under monitoring. In this study ASCT was found to be a safe procedure for improving survival rates of DLBCL patients with high intermediate to high aIPI risk. Also, the expression of Bcl-2 protein was found to be useful as one of the variables to be analysed in the therapeutic approach to these patient