Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow.

Polymerase chain reaction (PCR) amplification of the t(14;18) has been shown to be a highly sensitive method to detect minimal residual disease in patients with non-Hodgkin's lymphoma (NHL) whose tumors bear this translocation. The ideal tissue source to detect residual lymphoma would be from a previously involved lymph node. However, lymphoid tissue is rarely available once patients achieve complete remission. Although PCR amplification has been used to detect residual lymphoma cells in both bone marrow (BM) and peripheral blood (PB) of patients in complete remission, it is presently unknown whether BM and PB are equivalent tissue sources to detect residual disease. In the present study, we compared the clinical utility of the detection of residual lymphoma in both the BM and the PB of patients with advanced-stage non-Hodgkin's lymphoma before, at the time of, and after high-dose therapy and autologous BM transplantation (ABMT). The detection of residual lymphoma in either the BM or PB was associated with decreased disease-free survival. However, in the present study, 44% of patients who relapsed had no evidence of circulating lymphoma cells in their PB. At the time of BM harvest, PCR-detectable residual lymphoma cells were detected in 211 of 212 patients; although, in a subset of these patients analyzed, lymphoma cells were detected in the peripheral blood of only 49% of patients. When residual lymphoma cells within the autologous BM are infused into the patient these cells are rapidly detectable circulating in the PB in the patient. These cells continue to circulate during the immediate posttransplant period and be detectable in the PB in the majority of patients who are infused with marrow containing residual lymphoma. We conclude that BM is a more informative tissue source than PB in detecting minimal residual disease at the time of and after ABMT, and that contamination of PB early after ABMT appears to be the consequence of reinfusion of lymphoma cells within autologous marrow.

Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma.

Although molecular biologic techniques can now detect minimal numbers of residual cancer cells in patients in complete clinical remission, the clinical significance of minimal residual disease has never been conclusively established. If the detection of minimal residual disease predicts which patients will relapse, then therapy could be altered based upon the detection of these cells. The t(14;18) can be detected by polymerase chain reaction (PCR) amplification in 50% of patients with B-cell non-Hodgkin's lymphoma and allows detection of one lymphoma cell in up to 1 million normal cells. To determine the clinical significance of the detection of minimal residual lymphoma cells in the bone marrow (BM) PCR amplification was used to detect the presence of residual lymphoma cells after autologous BM transplantation (ABMT) in serial BM samples from 134 patients with B-cell lymphoma in whom a bcl-2 translocation could be detected. PCR analysis was performed on a total of 542 BM samples obtained while these patients were in complete remission. Disease-free survival was markedly increased in patients with no PCR-detectable lymphoma cells in the marrow compared with those in whom residual lymphoma cells were detected (P < .00001), and the presence of detectable lymphoma cells was associated with a 48-fold increase in the risk of relapse. Of the 77 patients (57%) with no PCR-detectable lymphoma cells in their most recent BM sample, none have relapsed. In contrast, all 33 patients (25%) who have relapsed had PCR-detectable lymphoma cells detected in their BM before clinical relapse occurred. In 19 patients (14%), residual lymphoma cells in the BM were detected early following transplantation and subsequently were no longer detectable, although these patients received no further therapy. In these patients, residual lymphoma cells may already have been irreversibly damaged by the high-dose therapy or an endogenous immune mechanism may be capable of eliminating residual lymphoma cells in some patients. Therefore, although the detection of minimal residual disease by PCR following ABMT in patients with lymphoma identifies those patients at high risk of relapse, the presence of residual minimal disease early after transplantation may not be associated with poor prognosis in a small subset of patients. Confirmatory studies will be required to determine more definitively the role of minimal disease detection to identify which patients require additional therapy.