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

Abstract

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.

Next‐generation sequencing‐based detection of circulating tumour DNA After allogeneic stem cell transplantation for lymphoma

“…An effective MRD assay that could identify lymphoma patients at increased risk for relapse after HSCT would be a powerful tool for developing relapse prevention strategies. However, MRD monitoring techniques are not available for most lymphoma subtypes, particularly when there is no peripheral blood involvement or characteristic chromosomal rearrangement (Gribben et al , , ; Corradini et al , ; Mancuso et al , ).…”

Rapid and sustained clearance of circulating lymphoma cells after chemotherapy plus rituximab: clinical significance of quantitative t(14;18) PCR monitoring in advanced stage follicular lymphoma patients†

“…Disease relapses are thought to arise from residual lymphoma cells that persist despite a complete clinical remission (minimal residual disease, MRD) and can only be detected by very sensitive methods, such as polymerase chain reaction (PCR; Gribben et al , 1991; Finke et al , 1993). Myeloablative chemotherapy with autologous bone marrow (BM) transplantation was the first widely available treatment option associated with the potential of eradicating residual lymphoma cells in a substantial proportion of patients (Gribben et al , 1993; Corradini et al , 1997). However, even though patients who achieved and maintained a MRD‐negative status had a significantly better progression‐free survival (PFS) (Gribben et al , 1993; Apostolidis et al , 2000), survival curves after myeloablative chemotherapy and autologous stem cell transplantation (ASCT) for FL showed a pattern of continuing relapses without clear evidence of a plateau (Freedman et al , 1999; Apostolidis et al , 2000).…”

Effective in vivo purging with rituximab and autologous peripheral blood stem cell transplantation in a woman with CD5 positive primary cutaneous diffuse large B‐cell lymphoma

“…One major obstacle to APBSCT is peripheral blood contaminations with lymphoma cells. Several studies have shown that reduction of the tumor burden in vivo and purging of autografts reduce the risk of contamination by lymphoma cells of the graft and may improve the outcome (12, 13). Rituximab can cause a rapid depletion of peripheral blood B cells.…”