Prognostic Model for Aggressive Non-Hodgkin Lymphoma.
Authors: Genadieva-Stavrik Sonja G. , Ivkovsi Ljube G. , Zografski Gorgi D. , Georgievski Borce A. , Stojanoski Zlate R. , Pivkova Aleksandra T. , Cevreska Lidija A. 
Published: October 2019

Abstract
There are two subgroups of the untreated lymphomas according to the outcome of the disease: indolent and aggressive. Unlike the indolent lymphoma, aggressive lymphomas are fatal in several weeks or months if untreated. However, the therapy available nowadays makes this group of patients with aggressive Non-Hodgkin’s lymphoma curable. Autologous stem cell transplantation used as first-line therapy can improve overall survival in selected group of patients with aggressive Non-Hodgkin lymphoma. To make the right and optimal therapeutic approach we need to stratify those patients in subgroups of patients with "high" and "low" risk, which was achieved with this study. This study comprises 211 patients with histopathology diagnosis of aggressive Non-Hodgkin’s lymphoma treated at the Department of Hematology in the period 1989–2002, which gave us the observation period of 6 to 183 months. There were 88 male patients, median age 53 years and 60 female, median age 52 years. Most of the patients were in the advanced clinical stage at the disease on the initial presentation of the disease, 24% of the patients in the third stage and 43% in the fourth stage. Bone marrow infiltration was found in 29%. Bcl-2 positively was confirmed in 26 cases by imunohistochemistry and there was proliferative index Ki-67 above 60% in 32 patients. Imunophenotipisation suggested that 80% of the cases are B-cell lymphoma. The patients were treated with antracicilin included regiments, most of them being CHOP regiment. After initial chemotherapy complete remission was achieved in 60%, partial response in 4% and there was no response in 32% with early deaths in 4%. At the end of the study 32% of the patients were alive and well, 32% were deceased and the reminder had unknown status. There was relapse of the disease in 50 patients with previous complete remission. According to the univariante analysis the following parameters had significantly influence the overall survival in the patients with aggressive Non-Hodgkin’s lymphoma: initial anemia, initial LDH, the stage of the disease, ECOG score, bone marrow infiltration, number of sites of extranodal infiltration, lymphoma subgroup according to various classification systems, morphology of the lymphoma cell, imunophenotype profile, percent of Ki-67 positively, bcl-2 positively, time to complete remission. The multiply progression analysis produce mathematical model through which we can anticipate the expected survival in each patients individually based on the statistically most influential prognostic markers, those achieving stratification of the patients in risk groups. In our study 32% of the patients with "high" risk are alive and "low risk patients have 70% 5-years overall survival. With the use of this prognostic model for aggressive Non-Hodgkin’s lymphoma we achieved risk based stratification of the patients even in the fourth stage of the disease with statistical significance. This prognostic model for aggressive Non-Hodgkin’s lymphoma enables the clinical hematologist to create the optimal individual therapeutic approach for each patient with aggressive Non-Hodgkin’s lymphoma. The patients with "high" risk are group of patients where beside the standard chemotherapy, use of aggressive chemotherapy and haematopoetic stem cell transplantation as well as the new therapeutic approaches would improve therapeutic results and overall survival.