Abstract

Seventy-four patients from a prospective randomized trial comparing autologous bone marrow (ABM) versus blood stem call (BSC) transplantation after high-dose chemotherapy for intermediate and high grade non-Hodgkin's lymphoma (NHL) were studied for the presence of residual lymphoma prior to transplantation. Pre-transplant bone marrow (BM), peripheral blood (PB) and the ABM or BSC harvest were studied by molecular assays immediately after collection and at weekly intervals after the initiation of in vitro cultures. B-NHLs with t(14;18) at the major breakpoint region (mbr) were monitored by detecting cells with the translocation. Other B-NHLs were monitored with tumour-specific primers and probes to the immunoglobulin heavy chain (IgH) gene complementary determining region (CDR) III. T-NHLs were similarly monitored using the T-cell receptor gamma chain gene V-J junctional region as the tumour-specific marker. Of the 74 patients, seven did not have adequate tumour biopsies for molecular characterization. Of the remaining 67 cases, 35 had identifiable markers for follow-up studies and 20/35 cases (52%) had tumour cells detected in either the pretransplant BM/PB samples or the ABM/BSC harvest. Residual tumours were detected at a high frequency in T-NHL (100%) and t(14:18)+ B-NHL (86%) but at a lower frequency in B-NHLs without t(14,18) (44%). In five cases, one or more of the samples were initially negative for residual lymphoma but became positive after a period of culture; additional studies confirmed that in vitro culture enhanced the sensitivity of turnout detection in about half of these samples. Molecular assay for minimal residual disease can be performed in the setting of multicentre prospective clinical trials. The substantial frequency of failure of obtaining tumour-specific IgH CDRIII sequences in paraffin-embedded B-NHLs argues for the storage of frozen tumour samples for possible molecular studies.

Original languageEnglish (US)
Pages (from-to)873-881
Number of pages9
JournalBritish Journal of Haematology
Volume99
Issue number4
DOIs
StatePublished - Jan 1 1997

Fingerprint

Lymphoma
Bone Marrow
Non-Hodgkin's Lymphoma
Residual Neoplasm
Neoplasms
Transplantation
T-Cell Receptor gamma Genes
Immunoglobulin Heavy Chain Genes
Immunoglobulin Heavy Chains
Tumor Biomarkers
Paraffin
Clinical Trials
Transplants
Biopsy
Drug Therapy
In Vitro Techniques

Keywords

  • IgH
  • Minimal residual disease
  • Non-Hodgkin's lymphoma
  • T-cell receptor

ASJC Scopus subject areas

  • Hematology

Cite this

The detection of minimal lymphoma by molecular and combined culture- molecular methods. / Wu, G. Q.; Sharp, John G; Wu, G.; Vose, Julie Marie; Greiner, Timothy Charles; Chan, W. C.

In: British Journal of Haematology, Vol. 99, No. 4, 01.01.1997, p. 873-881.

Research output: Contribution to journalArticle

@article{abb25b4793da4f21a977014262a4700f,
title = "The detection of minimal lymphoma by molecular and combined culture- molecular methods",
abstract = "Seventy-four patients from a prospective randomized trial comparing autologous bone marrow (ABM) versus blood stem call (BSC) transplantation after high-dose chemotherapy for intermediate and high grade non-Hodgkin's lymphoma (NHL) were studied for the presence of residual lymphoma prior to transplantation. Pre-transplant bone marrow (BM), peripheral blood (PB) and the ABM or BSC harvest were studied by molecular assays immediately after collection and at weekly intervals after the initiation of in vitro cultures. B-NHLs with t(14;18) at the major breakpoint region (mbr) were monitored by detecting cells with the translocation. Other B-NHLs were monitored with tumour-specific primers and probes to the immunoglobulin heavy chain (IgH) gene complementary determining region (CDR) III. T-NHLs were similarly monitored using the T-cell receptor gamma chain gene V-J junctional region as the tumour-specific marker. Of the 74 patients, seven did not have adequate tumour biopsies for molecular characterization. Of the remaining 67 cases, 35 had identifiable markers for follow-up studies and 20/35 cases (52{\%}) had tumour cells detected in either the pretransplant BM/PB samples or the ABM/BSC harvest. Residual tumours were detected at a high frequency in T-NHL (100{\%}) and t(14:18)+ B-NHL (86{\%}) but at a lower frequency in B-NHLs without t(14,18) (44{\%}). In five cases, one or more of the samples were initially negative for residual lymphoma but became positive after a period of culture; additional studies confirmed that in vitro culture enhanced the sensitivity of turnout detection in about half of these samples. Molecular assay for minimal residual disease can be performed in the setting of multicentre prospective clinical trials. The substantial frequency of failure of obtaining tumour-specific IgH CDRIII sequences in paraffin-embedded B-NHLs argues for the storage of frozen tumour samples for possible molecular studies.",
keywords = "IgH, Minimal residual disease, Non-Hodgkin's lymphoma, T-cell receptor",
author = "Wu, {G. Q.} and Sharp, {John G} and G. Wu and Vose, {Julie Marie} and Greiner, {Timothy Charles} and Chan, {W. C.}",
year = "1997",
month = "1",
day = "1",
doi = "10.1046/j.1365-2141.1997.4903295.x",
language = "English (US)",
volume = "99",
pages = "873--881",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - The detection of minimal lymphoma by molecular and combined culture- molecular methods

AU - Wu, G. Q.

AU - Sharp, John G

AU - Wu, G.

AU - Vose, Julie Marie

AU - Greiner, Timothy Charles

AU - Chan, W. C.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Seventy-four patients from a prospective randomized trial comparing autologous bone marrow (ABM) versus blood stem call (BSC) transplantation after high-dose chemotherapy for intermediate and high grade non-Hodgkin's lymphoma (NHL) were studied for the presence of residual lymphoma prior to transplantation. Pre-transplant bone marrow (BM), peripheral blood (PB) and the ABM or BSC harvest were studied by molecular assays immediately after collection and at weekly intervals after the initiation of in vitro cultures. B-NHLs with t(14;18) at the major breakpoint region (mbr) were monitored by detecting cells with the translocation. Other B-NHLs were monitored with tumour-specific primers and probes to the immunoglobulin heavy chain (IgH) gene complementary determining region (CDR) III. T-NHLs were similarly monitored using the T-cell receptor gamma chain gene V-J junctional region as the tumour-specific marker. Of the 74 patients, seven did not have adequate tumour biopsies for molecular characterization. Of the remaining 67 cases, 35 had identifiable markers for follow-up studies and 20/35 cases (52%) had tumour cells detected in either the pretransplant BM/PB samples or the ABM/BSC harvest. Residual tumours were detected at a high frequency in T-NHL (100%) and t(14:18)+ B-NHL (86%) but at a lower frequency in B-NHLs without t(14,18) (44%). In five cases, one or more of the samples were initially negative for residual lymphoma but became positive after a period of culture; additional studies confirmed that in vitro culture enhanced the sensitivity of turnout detection in about half of these samples. Molecular assay for minimal residual disease can be performed in the setting of multicentre prospective clinical trials. The substantial frequency of failure of obtaining tumour-specific IgH CDRIII sequences in paraffin-embedded B-NHLs argues for the storage of frozen tumour samples for possible molecular studies.

AB - Seventy-four patients from a prospective randomized trial comparing autologous bone marrow (ABM) versus blood stem call (BSC) transplantation after high-dose chemotherapy for intermediate and high grade non-Hodgkin's lymphoma (NHL) were studied for the presence of residual lymphoma prior to transplantation. Pre-transplant bone marrow (BM), peripheral blood (PB) and the ABM or BSC harvest were studied by molecular assays immediately after collection and at weekly intervals after the initiation of in vitro cultures. B-NHLs with t(14;18) at the major breakpoint region (mbr) were monitored by detecting cells with the translocation. Other B-NHLs were monitored with tumour-specific primers and probes to the immunoglobulin heavy chain (IgH) gene complementary determining region (CDR) III. T-NHLs were similarly monitored using the T-cell receptor gamma chain gene V-J junctional region as the tumour-specific marker. Of the 74 patients, seven did not have adequate tumour biopsies for molecular characterization. Of the remaining 67 cases, 35 had identifiable markers for follow-up studies and 20/35 cases (52%) had tumour cells detected in either the pretransplant BM/PB samples or the ABM/BSC harvest. Residual tumours were detected at a high frequency in T-NHL (100%) and t(14:18)+ B-NHL (86%) but at a lower frequency in B-NHLs without t(14,18) (44%). In five cases, one or more of the samples were initially negative for residual lymphoma but became positive after a period of culture; additional studies confirmed that in vitro culture enhanced the sensitivity of turnout detection in about half of these samples. Molecular assay for minimal residual disease can be performed in the setting of multicentre prospective clinical trials. The substantial frequency of failure of obtaining tumour-specific IgH CDRIII sequences in paraffin-embedded B-NHLs argues for the storage of frozen tumour samples for possible molecular studies.

KW - IgH

KW - Minimal residual disease

KW - Non-Hodgkin's lymphoma

KW - T-cell receptor

UR - http://www.scopus.com/inward/record.url?scp=0031471217&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031471217&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2141.1997.4903295.x

DO - 10.1046/j.1365-2141.1997.4903295.x

M3 - Article

C2 - 9432036

AN - SCOPUS:0031471217

VL - 99

SP - 873

EP - 881

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 4

ER -