Molecular monitoring of low grade non-Hodgkin's lymphoma by gene amplification

Abstract

Molecular monitoring by the polymerase chain reaction was used to detect and follow minimal disease in working formulation category B and C on non-Hodgkin's lymphoma. Rearrangement of the bcl-2 gene served as the target for gene amplification. Thirty patients were studied. Bone marrow histology was compared to PCR analysis of bone marrow aspirate and blood. PCR upstaged disease status in approximately 50% of patients. Results are shown from a patient whose disease was followed with PCR during chemotherapy from initial remission to relapse. We conclude that PCR of bone marrow and blood can be used to upstage disease status in low grade lymphoma and PCR of blood may be used to monitor response to treatment with obvious patient benefit. The general approach of molecular monitoring provides a means for appraising therapies in the setting of subclinical disease. Images Figure 2 Figure 3

Detection of bcl-2/JH rearrangement in follicular and diffuse lymphoma: concordant results of peripheral blood and bone marrow analysis at diagnosis

“…Therefore, it may reduce the need for more invasive examinations. Similar results, with a lesser degree of concordance between bone marrow and peripheral blood analysis, have recently been published (Hickish et al, 1991) indicating the PCR can be an effective means for clinical monitoring of low-grade lymphomas. However, the clinical significance of detecting minimal disease in bone marrow by PCR has still to be established and will require prolonged follow-up because of the natural history of FL with a median survival than can exceed 8 years in advanced stages.…”

High-dose therapy and stem cell transplantation in follicular lymphoma

“…This technique can detect one lymphoma cell in a background of 10 6 normal cells. Similar evidence for the presence of PCR-detectable occult disease in the presence of histologically normal marrow has been reported from other centers [11,12,21,22,23]. Considering the studies of genetically marked autologous marrow cells, which suggest that reinfused tumor cells contribute to relapse [24,25], in a disease such as follicular NHL several approaches have been taken to provide a tumor-free stem cell preparation.…”

Occult lymphoma cells prevalent in autologous marrow from non‐Hodgkin's diffuse lymphoma

“…PCR amplifications at the major and minor breakpoint regions of the bcl-2 translocation or IgH locus were performed using nested oligonucleotides as described elsewhere [21]. In samples with no detectable PCR product, PCR amplification was repeated using oligonucleotide primers specific for the V region of the gene encoding the human B-cell activation antigen B7 and confirmed that PCR-amplifiable DNA was present in each of the samples analyzed.…”