Treatment of aggressive lymphoma in relapse is difficult. Patients who initially present with these diseases often know they have a malignancy considered curable in many cases, and diagnosis of relapse can be devastating. For this reason, it is useful to know the individual patient's risk of relapse prior to starting initial therapy, since it may be appropriate to treat patients with poor prognoses with intensive programs or investigational studies. In the private practice setting, most patients with these diseases receive CHOP or similar cyclophosphamide and doxorubicin-containing regimens at the time of initial diagnosis. However, there are certain disease-related features which determine whether these patients have a high or low risk of relapse, and investigators are now using combinations of these features to determine which patients may be safely treated with CHOP and which may benefit from more intensive chemotherapy management. For example, the International Prognostic Factor Index system, now in common usage, delineates four different groups of patients with differing complete remission, freedom from progression, and overall survival rates. The Tumor Score System, developed at MDACC, delineates only two groups with very different survival rates, and may be a better scoring system for patients with diffuse large cell lymphomas, primarily because of its inclusion of the serum beta(2)-microglobulin level prior to treatment, an important predictor of relapse. In addition to pretreatment features, certain treatment-related factors are also important in determining the risk of relapse, including the dose of chemotherapy administered and the rapidity of response. Results of a gallium scan with SPECT imaging may be an important method of confirming complete response, and should be incorporated into treatment programs, whether the treatment is standard CHOP or an investigational program. For the patient with relapse or progressive disease following induction with CHOP or a similar regimen, the type of response to initial therapy plays an important role in determining potential response to salvage therapy, including high-dose therapy followed by stem cell rescue. Patients for whom initial treatment fails to achieve any response have a very poor chance of responding to any currently used standard-dose program for relapse. Those with partial responses have a better chance of responding to relapse therapy, but a high risk of disease progression or early relapse, and those with a prior complete response to initial therapy have a good chance of responding to relapse therapy, especially those in whom the complete response lasted more than a year. For these reasons, stem cell transplant (SCT) protocols routinely require complete response with initial therapy as a requirement for entry, although "good partial remission" may be acceptable at certain centers. Other limitations for SCT protocols include age greater than 60 or 65 years, significant chronic obstructive pulmonary, renal, or cardiac disease, a poor performance st...