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Abstract
The prognosis of aggressive lymphoma and the ability to categorize patients of aggressive lymphoma into relevant prognostically different groups had drawn much attention of medical oncology community in the last 3 decades. As the ability to stratifying patients with aggressive lymphoma into relevant risk groups will facilities both interpretations the results of clinical trials, and aids in treatment of patients using risk adapted therapy which expected to result in better outcome.
Data regarding prognostic factors in aggressive NHLs is abundant and sometimes confusing .Currently the IPI is the most extensively used factor to provide prognostic information for aggressive NHLs. However data on which IPI is depends came from patients treated in western countries and with well known variability in aggressive NHLs between different ethnic groups, a significant controversies had arose whether the IPI is validated to be applicable in patients with different etiological, biological and treatment related factors from Western patients’ population.
The first aim of the study was to determine the impact of different clinical, pathological and treatment related factors in the survival of patients with aggressive NHLs treated with combination chemotherapy and to identify prognostic factors for outcome.
The second aim of this study was to evaluate the ability of IPI (international prognostic index) in predicting the disease response to treatment, overall survival and relapse free survival rates in Egyptian population.
We retrospectively reviewed the records of 350 patients treated by anthracycline based combination chemotherapy for aggressive NHL in the interval between 1996 and 2005.We analyzed clinical parameters : age at presentation , sex , performance status , number and site of extranodal involvement , presence of B symptoms, presence of bulky disease , Ann Arbor stage , level of (LDH , ESR, HB, Albumin ,B2 microglobulin) at presentation, bone marrow involvement . Also analyzed pathological parameters (histological subtype) and treatment received (type of primary chemotherapy received , number of chemotherapy cycles received, number of patients received radiotherapy , usage of salvage chemotherapy in relapsed or refractory patients).
Response to primary combination chemotherapy, relapse free and overall survival was analyzed for each parameter and on multivariate analysis.
IPI and aaIPI were calculated for patients with completed risk factor data , chi square correlation analysis was used to determine the correlation between response to combination chemotherapy and both IPI and aaIPI. Survival analysis was carried out and correlated with both IPI, aaIPI.
Patients were followed for relapse free survival and overall survival a median of 45 and 48 months respectively. Disease recurrence was developed in 80 patients after median disease free interval of 18 months. At last follow up 200 of the 350 patients had died including 184 who died of NHL.
Five-year relapse free and overall survival rates on univariate analysis were 65% and 66% for patients with Low IPI risk group, 53% and 54% for patients with Low intermediate IPI risk group, 30% and 25% for patients with High intermediate IPI risk group, 29% and 19% for patients with High IPI risk group respectively .
After multivariate analysis independent predictors of short relapse free survival were the poor performance status, advanced Ann Arbor stage (stage III or IV), involvement of two or more extranodal sites, and low hemoglobin level at presentation.
Multivariate analysis to determine independent predictors of short overall survival was carried out and showed that older age at presentation, poor performance status, and involvement of two or more extranodal sites, advanced Ann Arbor stage (stage 3 or 4), high LDH level and low Albumin level all had an independent prediction of short overall survival.
This study points out different clinical, pathological and treatment related predictive factors of response to primary combination chemotherapy. Among them age at presentation, performance status, pretreatment (LDH level, HB level, Albumin level) number of extranodal site, Ann Arbor stage, dimension of largest tumor, bone marrow involvement can effectively predict disease response.
Again this study points out different clinical, pathological and treatment related prognostic factors of 5-yr RFS, 5-yr OS in patients with aggressive NHL. Among them, performance status, number of extranodal sites, Ann Arbor stage, can effectively predict relapse free survival at 5 years and age at presentation, performance status, number of extranodal sites, Ann Arbor stage, LDH level predict overall survival at 5 years.
Finally this study confirms the ability of IPI and its modified version aaIPI in predicting the response to chemotherapy, RFS and OS in Egyptian patient treated with anthracycline based combination chemotherapy for aggressive lymphoma.