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External beam radiation therapy (XRT) is frequently used to treat refractory disease sites or consolidate remission in patients with relapsed non-Hodgkin's lymphoma (NHL) prior to autologous bone marrow transplantation (ABMT). We report the long-term outcome and toxicities associated with this therapy. We uniformly treated 552 patients with NHL with total body irradiation, high-dose chemotherapy, and anti-B-cell monoclonal antibody-purged ABMT. Of these patients, 152 received XRT to the mediastinum, abdomen, or pelvis (n = 102) or other sites (n = 50) prior to ABMT. In this nonrandomized series, there was no difference in progression-free survival between patients treated with XRT and those not treated with XRT. For patients with indolent histology, there was no difference in overall survival between patients treated with XRT and those not treated with XRT. For patients with aggressive histology, the median overall survival time was 64 months in the XRT patients and 79 months in the patients not treated with XRT (P= .09). The risk of acute transplantation-related deaths was not influenced by prior XRT (P = .68). Of patients who received XRT, 12.5% developed secondary myelodysplasia compared with 5.8% of patients not receiving XRT (P = .01). Patients receiving XRT to the mediastinum or axilla had a significantly higher risk of late respiratory death (P = .002). In conclusion, XRT allows refractory patients to become eligible for transplantation and experience a disease-free survival interval equivalent to that of patients who do not receive XRT. However, a higher incidence of non-relapse-associated deaths was observed in patients who received XRT. Future work should explore alternative conditioning strategies and altered timing of XRT, in an attempt to limit these late toxicities.

The role of high-dose therapy and autologous stem cell transplantation in diffuse large B cell lymphoma (DLBCL) after transformation is controversial. We have retrospectively analyzed patients with chemosensitive disease and a history of follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma who underwent high-dose chemoradiotherapy and bone marrow transplantation (BMT) with anti-B cell monoclonal antibody-purged autologous marrow for DLBCL. Between December 1982 and August 1997, 27 patients underwent autologous BMT using a uniform ablative regimen with cyclophosphamide, total-body irradiation, and bone marrow purging. All patients received multiple chemotherapy regimens before autologous BMT. At bone marrow (BM) harvest, only 44% of patients were in complete remission, and overt BM infiltration was present in 37%. After cyclophosphamide and total-body irradiation, no treatment-related deaths were seen. Eleven of the 27 patients relapsed, and four patients developed myelodysplasia/acute myelogenous leukemia. In seven patients in whom pathologic studies were available after relapse, the histology remained DLBCL. Twelve patients remained alive and in complete remission with a median follow-up of 36 months (range 10-132). The disease-free survival and overall survival are estimated to be 46% (90% confidence interval 28-64) and 58% (40-76) at 5 years, respectively. Patients whose disease underwent histologic transformation within 18 months of their initial diagnosis of indolent lymphoma had significantly better overall survival. Selected patients with histologic transformation, particularly those whose transformation occurs early in the course of their disease and who remain chemosensitive, may experience prolonged survival after autoBMT.