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Blood, 1 April 2002, Vol. 99, No. 7, pp. 2541-2544
NEOPLASIA
Molecular follow-up in gastric mucosa-associated lymphoid tissue
lymphomas: early analysis of the LY03 cooperative trial
Francesco Bertoni,
Annarita Conconi,
Carlo Capella,
Teresio Motta,
Roberto Giardini,
Maurilio Ponzoni,
Ennio Pedrinis,
Domenico Novero,
Paolo Rinaldi,
Giovanni Cazzaniga,
Andrea Biondi,
Andrew Wotherspoon,
Barry William Hancock,
Paul Smith,
Robert Souhami,
Finbarr E. Cotter,
Franco Cavalli, and
Emanuele Zucca for the
International Extranodal Lymphoma Study Group and
the United Kingdom Lymphoma Group
From the Department of Experimental Haematology, Barts
and The London - Queen Mary's School of Medicine and Dentistry,
London, United Kingdom; Oncologia Medica, Istituto Oncologico della
Svizzera Italiana, Bellinzona, Switzerland; Divisione di Medicina
Interna, Dipartimento di Scienze Mediche, Università Amedeo
Avogadro del Piemonte Orientale, Novara, Italy; Istituto di Anatomia e
Istologia Patologica, Università dell'Insubria, Ospedale di
Circolo, Varese, Italy; Anatomia Patologica e Citologia, Ospedali
Riuniti, Bergamo, Italy; Patologia, OCS, Sondrio, Italy;
Dipartimento di Patologia, Ospedale San Raffaele, Milan, Italy;
Istituto di Patologia, Locarno, Switzerland; Universita' di Torino,
Torino, Italy; Ospedale Civile Infermi, Rimini, Italy; Centro di
Ricerca Tettamanti, Clinica Pediatrica Universita' Milano-Bicocca,
Monza, Italy; Histopathology, Royal Marsden Hospital, London, United
Kingdom; YCR Department of Clinical Oncology, Weston Park Hospital,
Sheffield, United Kingdom; MRC Clinical Trial Unit, London, United
Kingdom; Clinical Sciences, The Royal Free and University College
Medical School, London, United Kingdom.
 |
Abstract |
Gastric marginal zone lymphoma of mucosa-associated lymphoid tissue
(MALT)-type can regress after anti-Helicobacter pylori treatment. The International Extranodal Lymphoma Study Group, the
United Kingdom Lymphoma Group, and the Groupe d'Etude des Lymphomes de
l'Adulte have conducted a trial to ascertain whether the addition of
chlorambucil is of benefit after anti-H pylori therapy. At
the last interim analysis, 105 (55%) of 189 patients had achieved a
complete histologic remission after anti-Helicobacter therapy. To further assess the ability of treatment to eradicate the
lymphoma clone, we analyzed the gastric biopsies from a subset of the
patients by polymerase chain reaction (PCR) targeted to the
immunoglobulin heavy chain genes as a molecular marker for minimal
residual disease. Sixty-two cases were examined at diagnosis. Fifty-four cases were monoclonal by PCR. Forty-two of these patients achieved histologic complete remission (hCR) after
anti-Helicobacter treatment: 34 cases underwent molecular
follow-up analysis. Fifteen patients (44%) were in molecular remission
with a median follow-up of 2 years after antibiotic treatment and of 1 year after the achievement of hCR. Less than half of the patients with
MALT lymphoma can achieve sustained molecular remission after
anti-Helicobacter therapy. The presence of molecular
disease in the absence of histologic disease does not appear to be
associated with histologic relapse, but, given the indolent nature of
MALT lymphomas, a longer follow-up is needed.
(Blood. 2002;99:2541-2544)
© 2002 by The American Society of Hematology.
| |
Introduction |
Localized gastric marginal zone lymphoma of
mucosa-associated lymphoid tissue (MALT)-type is an indolent disease
with characteristic features.1,2 Gastric MALT lymphoma is
usually preceded by the occurrence of the Helicobacter
pylori-associated chronic gastritis, and it can regress after
antibiotic treatment. It is still not known whether antibiotics alone
might induce definitive cure of the lymphoma. The International
Extranodal Lymphoma Study Group (IELSG) and the United Kingdom Lymphoma
Group (UKLG), together with the Groupe d'Etude des Lymphomes de
l'Adulte (GELA), have conducted a trial to ascertain whether the
addition of chlorambucil is of benefit after anti-H pylori
therapy. At the last interim analysis, 105 (55%) of 189 patients had
achieved a complete histologic remission after antibiotics, and 15 lymphoma histologic relapses were observed in the total
group.3
To further assess the ability of treatment to eradicate the lymphoma
clone, we analyzed the gastric biopsies from a subset of the patients
by polymerase chain reaction (PCR) targeted to the immunoglobulin heavy
chain (IgH) genes.
| |
Patients, materials, and methods |
Patients with stage I primary gastric low-grade MALT lymphoma
were eligible. Histologic diagnosis was made according to the criteria
described in Isaacson and Norton4 and in the REAL/WHO classification.5,6 H pylori infection was
assessed at histologic examination (Giemsa stain or other specific
methods) or by serology (presence of immunoglobulin G anti-H
pylori antibodies). Baseline evaluations included patient history,
physical examination, routine laboratory tests, chest X-ray, computed
tomography scan of abdomen and pelvis, bone marrow aspirate and biopsy,
and gastric endoscopy with multiple biopsies. Patients were treated
with one of the following anti-Helicobacter regimens:
omeprazole 20 mg daily + clarithromycin 250 mg twice daily + tinidazole 500 mg twice daily for 1 week, omeprazole (40 mg twice daily
for 2 weeks) + amoxicillin (1 g 3 times daily for 2 weeks) + clarithromycin (250 mg 3 times daily for 2 weeks) or 2 weeks'
treatment with colloidal bismuth (120 mg 4 times daily) + metronidazole (400 mg 3 times daily) + tetracycline (500 mg 4 times daily) or amoxicillin (500 mg 4 times daily). Endoscopy was
repeated 2 to 3 months after treatment for H pylori
infection. If the latter had been eradicated, a further 4 to 6 months
had to elapse before assessment of tumor response by endoscopy.
Persistent H pylori infection was retreated with further
antibiotic treatment, with a maximum of 3 courses being given.
Patients were registered at the time of diagnosis, and, when in
complete remission, were assigned randomly to observation or to
chlorambucil (6 mg/m2 daily orally for 14 days repeated
every 28 days for 6 cycles). The trial had been approved by local
ethics committees, and written informed consent was obtained from all
the enrolled patients. Follow-up endoscopies had to be performed at
6-month intervals for the first 2 years, thereafter at yearly
intervals. At least 8 gastric biopsies had to be performed during
follow-up endoscopy.
Histologic examination of follow-up biopsies was performed by applying
the score proposed by Wotherspoon et al.7 Score 0-2 was
defined as histologic complete response (hCR), histologic score 3 as
partial response, and score 4-5 as persistent lymphoma. A panel of
pathologists reviewed all biopsies. Patients who failed to achieve hCR
after eradication of H pylori could still be randomly assigned to observation or chlorambucil if the physician felt it was
appropriate to do so. Otherwise, the nonresponders could be treated
with chemotherapy (chlorambucil as first choice).
DNA extraction, consensus IgH PCR amplification, and
allele-specific oligonucleotide PCR were performed as previously
described.8,9 Briefly, at diagnosis, samples were analyzed
with a combination of 2 different PCR assays to detect B-cell
monoclonality as molecular marker for follow-up tests. The third
complementarity-determining region was first amplified by seminested
PCR using the FR3A primer for the conserved framework region-3 (FR3)
segment of the variable region and the LJH and VLJH primers for the
joining region. A seminested PCR using the FR2A consensus primer was
then applied for the cases apparently polyclonal with FR3A-directed PCR.
PCR products were visualized on 10% and 7% nondenaturing
polyacrylamide gels for FR3A and FR2A amplicons, respectively. The presence of a distinct single band was considered diagnostic for monoclonality, and the presence of a smear of amplified products was
considered diagnostic for polyclonality. In case of no PCR products,
samples were assessed for the presence of amplifiable DNA with a PCR
using primers for the beta-globin gene. We defined molecular complete
remission (mCR) as the disappearance, in the DNA extracted from
follow-up samples in hCR, of the lymphoma monoclonal population present
in the diagnostic sample. We defined molecular relapse as the
reappearance, having achieved a mCR, of the lymphoma monoclonal band in
a follow-up sample, still in hCR. Two different follow-up calculations
were performed: from antibiotic treatment and starting from the
achievement of hCR.
| |
Results |
Sixty-two cases were analyzed at diagnosis (Figure
1). Fifty-four (87%; 95% confidence
interval [CI], 76%-94%) cases were monoclonal and 8 polyclonal by
PCR for the IgH genes: 40 were FR3A+, 14 were
FR3A /FR2A+, and 8 were
FR3A/FR2A. To assess the reason of
false-negative FR3A result, the VDJ region was sequenced in the
FR3A/FR2A+ group of cases (Table
1). Somatic mutations, or polymorphisms, were detected within the DNA sequence recognized by the FR3A primer in
10 (71%; 95% CI, 42%-92%) of 14. These data showed that the false
polyclonal PCR results with FR3A alone may be due to somatic mutations
within the VDJ regions that decrease the annealing ability of the
consensus primer.
View larger version (21K):
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| Figure 1.
Flowchart showing the number of patients analyzed by PCR
assay for the rearrangement of the IgH genes as molecular marker.
The 62 patients represent the group of cases among the patients
enrolled in the study, whose diagnostic material had been sent for
molecular assays. See text for further details.
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View this table:
[in this window]
[in a new window]
|
Table 1.
DNA sequence recognized by FR3A primer in 14 cases of
mucosa-associated lymphomic tissue lymphomas, apparently polyclonal
with FR3A/JH seminested polymerase chain reaction, but monoclonal
with FR2A/JH
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|
Forty-six (74%; 95% CI, 62%-84%) of the 62 cases achieved hCR. The
rate of hCR was 77% (95% CI,64%-84%) in monoclonal and 50% (95%
CI, 16%-84%) in polyclonal cases: 42 of 54 and 4 of 8, respectively.
Follow-up material for molecular biology assays was available in 34 cases among the 42 monoclonal cases that had achieved hCR. The
molecular follow-up data obtained in these cases is shown in Figure
2.
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| Figure 2.
Molecular follow-up in 34 patients with MALT lymphoma.
Black circles represent histologic disease; white, mCR; black and
white, persistent molecular disease in hCR. The follow-up is expressed
in months; the first time point is at the diagnosis.
|
|
Fifteen (44%; 95% CI, 27%-62%) of the 34 patients failed to achieve
mCR. Of the 19 (56%; 95% CI, 38%-73%) patients who achieved mCR, 16 had their mCR documented within 1 year after hCR, and 3 needed
a longer period of time (up to 2 years) to convert their hCR into a
molecular one. There were 6 molecular relapses, with 2 patients
achieving a second mCR. Fifteen patients (44%; 95% CI, 27%-62%)
were in mCR with a median follow-up of 2 years (6-72 months) after
antibiotic treatment and of 1 year (0-48 months) after the achievement
of hCR.
Five patients (15%; 95% CI, 5%-31%) experienced histologic
relapses. Case 11 had a first histologic relapse in the presence of
molecular disease, achieved a second remission (both histologic and
molecular), followed by a second transient histologic relapse, which
resolved again, but now with persistent molecular disease. Cases 12 and
14 showed a transient histologic relapse in the presence of molecular
disease. In case 14, the relapse was followed by the persistence of the
lymphoma clone. Case 24 had histologic relapses after mCR, then
followed by a second mCR. Case 25 had persistent B-cell monoclonality.
As a whole, there were 6 histologic relapses in 5 patients: 2 of them
occurred in mCR, 4 in the presence of molecular disease. In all the
cases, the lymphoma at relapse showed the same IgH monoclonal band
detected by PCR at the time of diagnosis.
| |
Discussion |
The indolent nature of the disease in most cases of MALT lymphoma
permits a conservative approach with antibiotic therapy, as the sole
initial treatment. It is still not clear if antibiotic therapy alone
can achieve complete lymphoma eradication. Thus, the IELSG, the GELA,
and the UKLG have conducted a trial to determine whether the addition
of chlorambucil is of benefit after anti-H pylori therapy.
The aim of this preliminary report on the molecular follow-up is not to
analyze the effect of chlorambucil after antibiotic treatments but
rather to determine the ability to correlate molecular residual disease
to clinical status. We present the molecular follow-up data obtained in
a series of patients enrolled in the trial. Of the patients treated
with anti-H pylori therapy, 74% achieved hCR, and 56% of
these patients had a mCR; 44% were still in mCR at the last follow-up
biopsy. Our data are similar to those reported by other
groups.10-12 After antibiotic treatment, it is common to
observe the persistence of the lymphoma clone, even in the absence of
histologic disease. Thiede et al11 found that the
persistent monoclonality might be due to aggregates of morphologically unsuspicious lymphocytes in the basal gastric mucosa. The relevance of
these cells bearing the same immunoglobulin rearrangement of the
lymphoma clone is not yet clear. Monoclonal populations have been
described in other situations with apparently no increased risk of
relapse or tumor occurrence. B-cell clones bearing the lymphoma-associated t(14;18)(q32;q21) can be detected in patients apparently cured for localized follicular lymphoma,13 and
tumor-associated translocations can be detected, even if at low levels,
in healthy individuals.14-16 Monoclonal B-cell populations
can be seen in benign H pylori-associated chronic
gastritis, Sjögren syndrome, and Hashimoto
thyroiditis.17 However, in all of the study patients the
clonal IgH rearrangement is initially detected from the malignant B
cells, and, as such, it may be regarded that the subsequent clonal
detection represents a marker from the initial malignant cells and,
thus, representative of minimal residual disease. Because the follow-up
of all published studies in MALT lymphoma is short, due to the indolent
natural history of the localized forms, it is not possible to rule out
a higher risk of relapse in cases that fail to achieve mCR.
Two of the 6 histologic relapses observed occurred despite the
previous achievement of an mCR. This finding might be explained by
unrepresentative biopsy samples, resulting in false-negative histologic
and molecular results. We agree with Thiede et al11 who
suggested 2 consecutive examinations are required before stating that a
patient is in complete remission to avoid misinterpretation.
In conclusion, the molecular follow-up analysis in gastric MALT
lymphoma reveals the persistence of the malignant clone in more than
half of the cases in hCR after antibiotic treatments. The significance
of this finding is still unclear. It is likely that the addition of
further genetic tests, such as the demonstration of the t(11;18) or
nuclear localization of the BCL10 protein,18 might improve
our understanding of the response of MALT lymphoma clone to antibiotic
treatment. Improved clinical and histologic criteria in assessing the
response to antibiotics and further follow-up and monitoring of
additional cases will define the significance of the persistent B-cell
monoclonality occurring in hCR and the role of chlorambucil after
antibiotic treatment in eradicating the lymphoma clone.
| |
Acknowledgments |
We thank Miss Michela Gisi for her expert technical assistance.
| |
Footnotes |
Submitted August 10, 2001; accepted November 20, 2001.
Supported by grants from the Swiss National Science Foundation (No.
32-45993.95) and from the Schweizerische Krebsliga/Krebsforschung Schweiz (No. AKT 623).
The publication costs of this
article were defrayed in part by
page charge payment. Therefore,
and solely to indicate this fact,
this article is hereby marked
"advertisement"
in accordance with 18 U.S.C.
section 1734.
Reprints: Francesco Bertoni, International Extranodal
Lymphoma Study Group (IELSG), Oncology Institute of Southern
Switzerland, Ospedale San Giovanni, 6500 Bellinzona, Switzerland;
e-mail: frbertoni{at}tin.it.
| |
References |
1.
Zucca E, Bertoni F, Roggero E, Cavalli F.
The gastric marginal zone B-cell lymphoma of MALT type.
Blood.
2000;96:410-419[Free Full Text].
2.
Isaacson PG, Muller-Hermelink HK, Piris MA, et al.
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). In:
Jaffe ES,Harris NL,Stein H,Vardiman JW, eds.
World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001:157-160
3.
Zucca E, Roggero E, Traulle C, et al.
Early interim report of the LY03 randomised cooperative trial of observation vs chlorambucil after anti-Helicobacter therapy in low-grade gastric lymphoma [abstract].
Ann Oncol.
1999;10 (suppl 3):25.
4.
Isaacson PG, Norton AJ.
Malignant lymphoma of the gastrointestinal tract. In:
Isaacson PG,Norton AJ, eds.
Extranodal Lymphomas. Edinburgh United Kingdom: Churchill Livingstone; 1994:15-65
5.
Harris NL, Jaffe ES, Diebold J, et al.
The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997.
Ann Oncol.
1999;10:1419-1432[Abstract/Free Full Text].
6.
Harris NL, Jaffe ES, Stein H, et al.
A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group.
Blood.
1994;84:1361-1392[Free Full Text].
7.
Wotherspoon AC, Doglioni C, Diss TC, et al.
Regression of primary low-grade B-cell gastric lymphoma of mucosa- associated lymphoid tissue type after eradication of Helicobacter pylori.
Lancet.
1993;342:575-577[CrossRef][Medline]
[Order article via Infotrieve].
8.
Zucca E, Bertoni F, Roggero E, et al.
Molecular analysis of the progression from Helicobacter pylori-associated chronic gastritis to mucosa-associated lymphoid-tissue lymphoma of the stomach.
N Engl J Med.
1998;338:804-810[Free Full Text].
9.
Conconi A, Bertoni F, Pedrinis E, et al.
Nodal marginal zone B-cell lymphomas may arise from different subsets of marginal zone B lymphocytes.
Blood.
2001;98:781-786[Abstract/Free Full Text].
10.
Savio A, Franzin G, Wotherspoon AC, et al.
Diagnosis and posttreatment follow-up of Helicobacter pylori-positive gastric lymphoma of mucosa-associated lymphoid tissue: histology, polymerase chain reaction, or both?
Blood.
1996;87:1255-1260[Abstract/Free Full Text].
11.
Thiede C, Wundisch T, Alpen B, et al.
Persistence of monoclonal B cells after cure of Helicobacter pylori infection and complete histologic remission in gastric mucosa-associated lymphoid tissue B-cell lymphoma.
J Clin Oncol.
2001;19:1600-1609[Abstract/Free Full Text].
12.
Montalban C, Santon A, Boixeda D, et al.
Treatment of low grade gastric mucosa-associated lymphoid tissue lymphoma in stage I with Helicobacter pylori eradication. Long-term results after sequential histologic and molecular follow-up.
Haematologica.
2001;86:609-617[Abstract/Free Full Text].
13.
Finke J, Slanina J, Lange W, Dolken G.
Persistence of circulating t(14;18)-positive cells in long-term remission after radiation therapy for localized-stage follicular lymphoma.
J Clin Oncol.
1993;11:1668-1673[Abstract/Free Full Text].
14.
Biernaux C, Loos M, Sels A, Huez G, Stryckmans P.
Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individuals.
Blood.
1995;86:3118-3122[Abstract/Free Full Text].
15.
Dolken G, Illerhaus G, Hirt C, Mertelsmann R.
BCL-2/JH rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases.
J Clin Oncol.
1996;14:1333-1344[Abstract/Free Full Text].
16.
Trumper L, Pfreundschuh M, Bonin FV, Daus H.
Detection of the t(2;5)-associated NPM/ALK fusion cDNA in peripheral blood cells of healthy individuals.
Br J Haematol.
1998;103:1138-1144[CrossRef][Medline]
[Order article via Infotrieve].
17.
Bertoni F, Cotter FE, Du M.
MALT lymphoma: genetics and biology. In:
Bertoni F,Zucca E, eds.
MALT Lymphomas. Georgetown, TX: Eurekah.com; 2002. Available at http://www.eurekah.com/register/oncology.html.
18.
Liu H, Ye H, Dogan A, et al.
T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10.
Blood.
2001;98:1182-1187[Abstract/Free Full Text].
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Top
Abstract
Introduction