The inability to purge residual lymphoma cells was the most important prognostic indicator in predicting relapse. These results provide evidence of the clinical usefulness of ex vivo purging of autologous bone marrow in the treatment of patients with lymphoma and suggest that the reinfusion of malignant cells in autologous marrow contributes to relapse

A s bstract. The expression of B cell associated and restricted antigens on tumor cells isolated from 138 patients with non-T cell acute lymphoblastic leukemia (non-T cell ALL) was investigated by flow cytometric analysis by means of a panel of monoclonal antibodies. Tumor cells from these patients could be assigned to one of four subgroups: human leukocyte antigen-DR-related Ia-like antigens (Ia) alone (4%, stage I); IaB4 (14%, stage II); IaB4CALLA (33%, stage III); and IaB4CALLAB, (49%, stage IV). The expression of B cell-restricted antigens (B4 and B,) and rearrangements of Ig heavy chain genes provided strong evidence for the B cell lineage of stages II, III, and IV tumors. The lineage of the Ia alone group is still unknown. The B4 antigen was expressed on -95% of all non-T cell ALLs tested, and given its absence on T cell and myeloid tumors, it appears to be an exceptional marker to define cells of B lineage.The demonstration that Ia alone, IaB4, IaB4CALLA, and IaB4CALLAB, positive cells can be readily identified by dual fluorescence analysis in normal fetal and adult bone marrow provided critical support for the view that these leukemic pre-B cell phenotypes were representative of the stages of normal pre-B cell differentiation. It was interesting that the IaB4+ cell was more frequently identified in fetal bone marrow than in adult marrow, whereas the predominant cell found in adult marrow expressed

Despite advances in the primary treatment of non-Hodgkin's lymphoma, relapse is common and treatment after relapse is unsatisfactory. Autologous bone marrow transplantation, although sometimes successful, has generally had disappointing results. We conducted a trial of such transplantation in patients with relapsed non-Hodgkin's lymphoma, using strict criteria in selecting patients; we included only those in whom disease was minimal after conventional treatment (nodal disease less than 2 cm and bone marrow involvement less than or equal to 5 percent on histologic examination) and whose tumor cells expressed the B1 antigen. Forty-nine patients meeting these criteria received cyclophosphamide and whole-body irradiation supported by transplantation of autologous bone marrow that had been treated in vitro with anti-B1 monoclonal antibody and complement. All patients had features of a poor prognosis, including relapse from primary chemotherapy, histologic conversion to more aggressive disease, and extra-nodal dissemination. Thirty-three patients had a history of bone marrow involvement--16 at the time that marrow was obtained. Hematologic and immunologic engraftment was achieved in all patients. Only two treatment-related deaths occurred, from venoocclusive disease of the liver and intracerebral hemorrhage, respectively. Disease-free remission without maintenance therapy has lasted from greater than 2 to greater than 52 months in 34 patients (median follow-up, greater than 11 months). These results are similar to those obtained in patients with advanced, high-grade non-Hodgkin's lymphoma treated with primary combination chemotherapy. This study demonstrates that autologous bone marrow transplantation has tolerable toxicity and high efficacy in a subset of patients who are otherwise incurable but still responsive to cytoreductive therapy. The results suggest a role for such transplantation in the treatment of selected patients with newly diagnosed non-Hodgkin's lymphoma.

These studies suggest that, despite careful attention to sterile procedures, low-level contamination of hematopoietic stem cell components can be introduced before or during manipulation as well as at thawing, and that standards for monitoring of the procedures for collection, processing, cryopreservation, thawing, and transfusion of hematopoietic progenitor cells are necessary.

One hundred patients with B-cell non-Hodgkin's lymphoma (NHL) in sensitive relapse or incomplete first remission underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MAb)-treated autologous bone marrow transplantation (ABMT). These patients demonstrated good performance status with a Karnofsky score of 80% or greater. The majority of these patients had one or more adverse prognostic features including a failure to achieve a complete remission (CR) with conventional combination chemotherapy (37 patients), bone marrow infiltration (69 patients), a history of extranodal disease other than bone marrow infiltration (42 patients), and histologic conversion (18 patients). At the time of ABMT, only 52 patients were in CR; however, all patients achieved a minimal disease state following conventional intensive therapy. Moreover, at the time of marrow harvest, 37 of these patients had histologic evidence of lymphoma cells infiltrating the marrow. Following high-dose ablative therapy, two acute in-hospital treatment-related deaths were observed. Two late deaths were observed, not due to recurrent lymphoma. Of the remaining 96 patients, 61 are in unmaintained CR with a median follow-up of 13 months. Kaplan-Meier actuarial analysis predicts 50% probability of disease-free survival (DFS) at 37.8 months. This very low treatment-related mortality provides the rationale to apply high-dose therapy and ABMT as consolidative therapy for patients in first remission who are at high risk for relapse following conventional therapy.