The International Non-Hodgkin's Lymphoma Prognostic Factors Project aimed to develop a predictive model for aggressive non-Hodgkin's lymphoma based on clinical characteristics before treatment. The study included 3273 patients from 16 institutions in the United States, Europe, and Canada who were treated with combination chemotherapy containing doxorubicin between 1982 and 1987. The model, known as the International Index, identified five independent prognostic factors: age (≤60 vs. >60 years), tumor stage (stage I or II vs. stage III or IV), number of extranodal disease sites (≤1 vs. >1), performance status (0 or 1 vs. ≥2), and serum LDH level (≤1 times normal vs. >1 times normal). These factors were used to define four risk groups: low risk (0 or 1 factor), low intermediate risk (2 factors), high intermediate risk (3 factors), and high risk (4 or 5 factors). The International Index was equally predictive in a validation sample and showed distinct survival rates across the risk groups. An age-adjusted International Index was also developed for younger patients (≤60 years), using tumor stage, LDH level, and performance status. The models were validated in two recent series of over 2000 patients treated with intensive third-generation regimens. The International Index can be used to identify patients at high risk who may benefit from experimental approaches, while the age-adjusted index can be used for younger patients in more intensive trials. The models also showed that clinical features correlated with an increased risk of relapse were associated with a decreased likelihood of initial complete remission, highlighting the need for improved therapeutic approaches for high-risk patients.The International Non-Hodgkin's Lymphoma Prognostic Factors Project aimed to develop a predictive model for aggressive non-Hodgkin's lymphoma based on clinical characteristics before treatment. The study included 3273 patients from 16 institutions in the United States, Europe, and Canada who were treated with combination chemotherapy containing doxorubicin between 1982 and 1987. The model, known as the International Index, identified five independent prognostic factors: age (≤60 vs. >60 years), tumor stage (stage I or II vs. stage III or IV), number of extranodal disease sites (≤1 vs. >1), performance status (0 or 1 vs. ≥2), and serum LDH level (≤1 times normal vs. >1 times normal). These factors were used to define four risk groups: low risk (0 or 1 factor), low intermediate risk (2 factors), high intermediate risk (3 factors), and high risk (4 or 5 factors). The International Index was equally predictive in a validation sample and showed distinct survival rates across the risk groups. An age-adjusted International Index was also developed for younger patients (≤60 years), using tumor stage, LDH level, and performance status. The models were validated in two recent series of over 2000 patients treated with intensive third-generation regimens. The International Index can be used to identify patients at high risk who may benefit from experimental approaches, while the age-adjusted index can be used for younger patients in more intensive trials. The models also showed that clinical features correlated with an increased risk of relapse were associated with a decreased likelihood of initial complete remission, highlighting the need for improved therapeutic approaches for high-risk patients.