ADVANCED DIFFUSE NON-HODGKINS-LYMPHOMA - ANALYSIS OF PROGNOSTIC FACTORS BY THE INTERNATIONAL INDEX AND BY LACTIC-DEHYDROGENASE IN AN INTERGROUP STUDY

Background. Recent data have suggested that there are no differences a mong various anthracycline-based chemotherapy regimens [including cycl ophosphamide, vincristine, methotrexate, and prednisone (CHOP), methot rexate, calcium leucovorin, bleomycin, doxorubicin, cyclophosphamide, and dexamethasone (m-BACOD), methotrexate, doxorubicin, cyclophosphami de, vincristine, prednisone, and bleomycin (MACOP-B), and cyclophospha mide, doxorubicin, etoposide, prednisone, cytosine arabinoside, bleomy cin, vincristine, methotrexate, and calcium leucovorin (PROMACE-cyta-B OM)] in patients with diffuse aggressive lymphomas. Because outcome ap pears to depend on certain prognostic factors, risk groups can be iden tified. Therefore, these prognostic factors were examined for their co rrelations with survival, time-to-treatment failure (TTF), and disease free survival (DFS) in a group of patients with diffuse aggressive no n-Hodgkin's lymphoma who were treated on a single randomized trial wit h either CHOP or m-BACOD. Methods. From July 1984 to January 1988, 392 patients with diffuse large cell or diffuse mixed non-Hodgkin's lymph oma were enrolled in an Intergroup study and were randomly assigned to treatment with CHOP or m-BACOD chemotherapy. Of these, 325 were eligi ble for response, toxicity, and survival analysis, and the results wer e reported. The survival and TTF results now have been updated. The 28 6 patients who had lactic dehydrogenase (LDH) data available at study entry were analyzed for prognostic features according to the Internati onal Index criteria and using Martingale Residuals for proportional ha zards regression. Results. There were no differences in survival, TTF, and disease free survival between groups of patients treated with eit her CHOP or m-BACOD. In addition, analysis using the International Ind ex criteria confirmed that patients in the lower risk groups had bette r outcome than patients in the higher risk groups (5-year survival was 56 and 58% for low and low/intermediate risk groups, respectively, an d 37% and 31% for high/intermediate and high risk groups, respectively ). There were, however, no differences in survival, disease free survi val, or TTF within any risk group when treatment with CHOP or m-BACOD were compared. In addition, analysis using Martingale residuals for pr oportional hazards regression identified LDH level (> 3 X normal) as a n important prognostic factor that was not captured by the Internation al Index. Thus, 5-year survival was 57% if LDH was normal or below, 42 % if LDH was 1-3 X normal, and 21% if LDH was > 3 X normal. Conclusion . In patients with advanced diffuse large cell or diffuse mixed non-Ho dgkin's lymphoma, there are no differences in outcome that can be attr ibuted to treatment with CHOP vs. m-BACOD; this holds for any prognost ic group identified by the International Index. However, the level of LDH at time of study entry is an important prognostic factor that is p redictive of survival and may help to identify candidates for future c linical trials.