|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-04-1279.
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
From the International Extranodal Lymphoma Study Group
(IELSG). A complete list of the investigators of the IELSG appears in
"Appendix 1" and "Appendix 2."
A retrospective survey of patients with pathologically reviewed
extragastric mucosa-associated lymphoma tissue (MALT) lymphomas from 20 institutions was performed. A total of 180 patients with histologically
confirmed diagnosis of extragastric MALT lymphomas were studied. Their
median age was 59 years (range, 21-92 years). Ann Arbor stage I disease
was present in 115 patients (64%) and stage II disease in 16 (9%).
Most cases were in the low or low-intermediate risk groups according to
the International Prognostic Index (IPI). Forty-one (23%) patients had
involvement of more than one extranodal site at diagnosis and in 24 cases (13%) the lymphoma presented at multiple mucosal sites (9 of
them with only mucosal involvement, without bone marrow or nodal
disease). Lymph node involvement was present in 21%. Patients were
treated with a variety of therapeutic strategies, including
chemotherapy in 78 cases. The median overall survival (OS) was not
reached; the 5-year OS rate was 90% (95% CI, 82%-94%), the 5-year
cause-specific survival (CSS) was 94% (95% CI, 87%-97%), and the
5-year progression-free survival (PFS) was 60% (95% CI, 50%-70%).
Multivariate analysis showed that Ann Arbor stage was significantly
associated with longer OS, nodal involvement with longer CSS, and
favorable IPI score with better PFS. At a median follow-up of 3.4 years, 48 patients (27%; 95% CI, 20%-34%) had a relapse, 6 (3%;
95% CI, 1%-7%) showed histologic transformation, and 18 (10%; 95%
CI, 6%-15%) experienced the development of a second tumor. Our data
confirm the indolent nature of nongastric MALT lymphomas and the high
rate of patients presenting with disseminated disease, which, when
limited to mucosal sites, was not associated with a poorer outcome.
(Blood. 2003;101:2489-2495) The group of lymphomas previously classified as
low-grade MALT lymphomas includes a number of extranodal B-cell
neoplasms defined as extranodal marginal zone B-cell lymphomas of
mucosa-associated lymphoid tissue (MALT lymphoma) in the Revised
European-American Classification of Lymphoid Neoplasms
(REAL)1 and in the World Health Organization (WHO)
classification of neoplastic diseases of the hematopoietic and lymphoid
tissues.2
Far from being rare, MALT lymphomas account for approximately 7% to
8% of all non-Hodgkin lymphomas (NHLs), being the third most frequent
histologic subtype (after diffuse large B-cell lymphoma and follicular
lymphoma).2,3 The stomach is the most common and
best-studied site of involvement.4 MALT lymphomas have also been described in various nongastrointestinal sites, such as
salivary gland, thyroid, skin, conjunctiva, orbit, larynx, lung,
breast, kidney, liver, prostate, and even in the intracranial dura.5-20 Involvement of multiple mucosal sites is often
present and disseminated disease appears to be more common in
nongastrointestinal MALT lymphomas, in which one fourth of cases has
been reported to present with involvement of multiple mucosal sites or
nonmucosal sites such as bone marrow.8,9,21,22 It has been
postulated that this dissemination may be due to the specific
expression of special homing receptors or adhesion molecules on the
surface of the B cells of MALT.23-25 Nongastric MALT
lymphomas have been difficult to characterize because these tumors,
numerous when considered together, are distributed so widely throughout
the body that it is difficult to assemble adequate series of any given site. The International Extranodal Lymphoma Study Group (IELSG) conducted an analysis of a large series of patients who were diagnosed as having nongastric MALT lymphomas with the aim of better
characterizing this disease entity.
We considered eligible for the study the patients with an
initial diagnosis of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) according to the
REAL/WHO classification criteria and presenting with a clinically dominant nongastric site of localization. The primary site of lymphoma
involvement was operationally defined as the clinically dominant
extranodal component, which requires diagnostic investigation and to
which primary treatment must often be directed.
Standardized forms were submitted to participating institutions to
obtain data on age, sex, Eastern Cooperative Oncology Group (ECOG)
performance status (PS), disease stage defined according to the Ann
Arbor criteria,26 location of extranodal disease, presence
of B symptoms, serum lactate dehydrogenases (LDH) and All cases were reviewed by a panel of pathologists to confirm
the diagnosis and to stratify them according to the percentage of large
cells (< 10% versus > 10%). Immunophenotyping was performed whenever required to exclude other small lymphocytic neoplasms. The
presence of solid clusters (> 20 cells) or sheetlike proliferations of large cells was considered to indicate transformation into a diffuse
large cell lymphoma and was an exclusion criteria. A preliminary
analysis of this series has been already presented,28,29 including 66 additional patients from a series that underwent separate
histology evaluation and had already been published
elsewhere.9 In the present analysis, only the cases
reviewed by the IELSG pathology panel were included. The databases of
the 20 participating centers included 365 eligible patients whose
lymphoma diagnosis was made from 1983 to 1999. Adequate pathologic
material for histologic revision was available in 243 cases: 52 patients were ineligible on review (20 with diffuse large B-cell
lymphoma with accompanying MALT lymphoma component, 9 with reactive
lymphoid proliferation, 9 with mantle cell lymphoma, 8 with follicular
lymphoma, 3 with plasmacytoma, 2 with peripheral T-cell lymphoma, and 1 with lymphoplasmacytoid lymphoma). Of the remaining 191 cases, 2 patients were excluded from the study because of a primary gastric
localization and 9 because of incomplete or inadequate follow-up data.
The staging procedures were not standardized but varied depending on
different centers and periods and included chest and abdomen imaging
investigations (computed tomography [CT] or ultrasound [US] scans),
digestive tract endoscopic investigations, and bone marrow biopsy.
All evaluations of clinical stage and response to treatment were based
on the original data recorded by local physicians. Complete remission
(CR) was defined as the disappearance, for at least 1 month, of all
clinical evidence of the disease, including the normalization of all
laboratory values and radiographs that were abnormal at presentation
including a normalization of bone marrow, if initially involved. A CR
to the initial treatment was assigned when patients with stage I
disease had no evidence of disease after diagnostic surgical excision
with or without subsequent adjuvant chemotherapy or radiation. Partial
remission (PR) was defined as a more than 50% reduction in the largest
dimension of involved sites. Stable disease (SD) was defined as a less
than 50% regression or less than 50% increase of the known sites of disease. Relapsing or progressive disease (PD) was defined as appearance of any new lesion or increase of at least 50% in the size
of the previously involved sites. Statistical analysis was conducted
using the STATA 5.0 software package (Computing Resource Centre, Santa
Monica, CA). According to the National Cancer Institute (NCI)
criteria,30 overall survival (OS) was calculated from time
of diagnosis to time of death from any cause or last follow-up. Progression-free survival (PFS) was measured from time of diagnosis to
the time of primary treatment failure, relapse/progression, or death
from lymphoma. Cause-specific survival (CSS) was measured from time of
diagnosis to the time of death from disease or treatment-related causes. The median follow-up was computed by the reverse Kaplan-Meier method.31 Survival probabilities were calculated using the
life table method and survival curves were estimated by the method of
Kaplan-Meier and differences between curves were analyzed using the
log-rank test.32 The binomial exact 95% confidence
interval (95% CI) was calculated for percentages. The
Pathology review
Patient characteristics
Treatment and outcome A total of 174 (97%) patients had lymphoma-directed treatment; in the remaining, a "wait and see" policy was adopted. Primary treatment included chemotherapy in 78 patients (in 36 cases with an anthracycline-based regimen); 12 of them had a combined modality approach (chemoradiotherapy). Forty-one patients had radiotherapy as the sole primary treatment. Sixty-eight patients had a surgical resection, alone (n = 27), followed by chemotherapy (n = 14), radiotherapy (n = 22), or both (n = 5). Four patients received interferon- therapy and one, with a skin localization, had
tumor regression after antibiotic therapy against Borrelia
burgdorferi.34 Table 3
shows the first-line therapy according to the Ann Arbor stage.
A total of 139 patients (77%; 95% CI, 70%-83%) patients achieved a CR and 29 (16%; 95% CI, 11%-22%) a PR after initial therapy with an overall response rate (ORR) of 93% (95% CI, 89%-97%). Among patients with stage IV disease, 28 (57%) had a CR and 17 (35%) a PR with an ORR of 92%. Among the patients receiving chemotherapy, the ORR was 92% with 72% CRs. The use of regimens containing anthracycline did not significantly improve the response rate in comparison with a single alkylating agent or CVP (cyclophosphamide, vincristine, prednisone) regimen, neither in localized nor in advanced stage disease. Moreover, a chemotherapy program, with or without anthracycline, had no significant effect on OS, CSS, and PFS, even in disseminated disease. The median follow-up time was 3.4 years with 75% of cases followed for
at least 4.9 years. The median OS was not reached. The estimated 5-year
OS was 90% (95% CI, 82%-94%) in the whole series (Figure
1). Twelve patients died, 6 patients from
lymphoma progression and 4 of them after histologic transformation. All the lymphoma-related deaths occurred within 4 years from diagnosis. Table 4 provides information regarding
the causes of death and their relationship with the main prognostic
factors. The estimated 5-year CSS was 94% (95% CI, 87%-97%; Figure
1). The 5-year PFS was 60% (95% CI, 50%-70%), with a median PFS of
8 years (Figure 1). Table 5 shows the
outcome according to the primary site of localization, whereas Table
6 summarizes the main clinical features at diagnosis according to the primary extranodal localization.
Analysis of prognostic factors At univariate analysis, limited stage, a single extranodal site of involvement, absence of nodal involvement, and favorable IPI score were the main clinical features significantly associated with better OS, CSS, and PFS (Table 7). Normal serum LDH levels were associated with longer OS and PFS. An increased number of large cells (ie, ranging between 10% and 20%) displayed no statistically significant association with outcome. However, the cases with less than 10% large cells had a longer median PFS in comparison with those with 10% to 20% large cells (8 years versus 4 years), but this difference was not statistically significant, probably because of the very small number of events.
Within the category of stage IV disease, only the subgroup of patients
with involvement of multiple MALT sites had a better survival (5-year
OS, 100% versus 70%) than the remaining cases with stage IV,
comprising those with multiorgan involvement or multifocal involvement
of a single organ and additional bone marrow or nodal involvement
(Figure 2).
Table 8 summarizes the results of
multivariate analysis. Despite the obvious limitations of Cox models
with restricted number of events (only 10% death rate at 5 years), Ann
Arbor stage retained its prognostic significance at multivariate
analysis of OS. Nodal involvement was associated with a significantly
higher relative risk of cause-specific death; a favorable IPI score was
associated with a better PFS (Figures
2-4).
Histologic transformation and development of second tumor Histologic transformation into diffuse large B-cell lymphoma was reported in 6 cases (3%; 95% CI, 1%-7%); notably, all these cases had no excess of large cells in their initial histology. The variables significantly associated with high-grade transformation were primary hepatic localization (P = .005), advanced stage disease (P = .03), and serologic evidence of previous HCV infection (P = .002). Large B-cell transformation was associated with a worse CSS (P < .05).Eighteen patients (10%; 95% CI, 6%-15%) experienced the development of a second tumor.
Extranodal marginal zone B-cell lymphoma is a discrete clinicopathologic entity arising in the MALT. Two types of MALT can be identified in disparate organs that do not correspond to peripheral sites of the immune system. The native type consists of lymphoid tissue physiologically present in the gut (eg, Peyer patches), whereas acquired MALT develops in sites of inflammation in response to either infectious conditions, such as Helicobacter pylori gastritis, or autoimmune processes, such as Hashimoto thyroiditis or myoepithelial sialadenitis associated with Sjögren syndrome.4,35,36 In the context of these prolonged lymphoid reactive proliferations, the growth of a pathologic clone can progressively replace the normal lymphoid population, giving rise to a MALT lymphoma.5,6,37,38 The peculiar pathogenetic features of primary gastric MALT lymphomas, with their implications on the clinical behavior of this entity,4 and data suggesting a distinct pattern of disease relapse and survival of the primary intestinal localizations39 led us to collect a series of primary nongastric MALT lymphomas including primary lymphomas of the small and large bowel. In our series of cases collected from a variety of cancer centers, most of the patients had the lymphoma primarily localized in the salivary glands, in the ocular adnexa, or in the skin, but primary localizations in the lungs and upper airways were also often reported. The presence of a previous autoimmune disease, most often Sjögren syndrome, was significantly associated with a primary lymphoma of the salivary glands. A primary parotid lymphoma was also significantly associated with evidence of HCV infection. This result supports the possible, but controversial,40,41 role of HCV infection in the pathogenesis of salivary gland lymphomas, a role suggested at the molecular level by a peculiar pattern of rearrangement of the antigen receptor genes of salivary MALT lymphomas,42 analogous to the pattern of other HCV-related NHLs.43,44 A variable rate of large cells represents a common feature in marginal-zone lymphomas1,2; the presence of clusters or sheets of large cells suggests the emergence of a transformed clone and has been indicated as a marker of initial transformation into aggressive histiotypes. Many efforts have been made in identifying reliable criteria for the stratification of the low-grade lesions45 with respect to the percentage of infiltrative large cells, but they are confronted with the scarce reproducibility of the morphologic criteria.8 In the present series of histologically reviewed cases, despite the presence of a trend toward a poorer outcome for cases with an increased large cell rate, the small number of events probably prevented the statistical relevance of the finding. Stage IV disease was present in more than one fourth of patients and multiple MALT organ localizations were observed at diagnosis in 13% of all patients. This proportion, apparently higher than that observed in primary gastric localizations, is comparable to those reported in other series and contradicts the common opinion of the MALT lymphomas as a typically localized disease,8,9 thus emphasizing the need of complete staging procedures in patients with MALT lymphomas.46 The preferential dissemination within the organs of the MALT system, likely due to the specific expression of special homing receptors or adhesion molecules on the surface of the B cells of MALT,23-25 may reflect an earlier phase of the natural history of the disease. According to this observation, in the group of patients with disseminated disease, the presence of multiple MALT-organ localizations without bone marrow or nodal disease appears to be associated with a better prognosis (Figure 2). On the contrary, the presence of nodal involvement or stage IV disease (characterized by cases with both nodal and extranodal disease and including cases with bone marrow involvement) identifies a group of patients with a worse prognosis (possible expression of a more advanced disease where the distribution of the B cells does not reflect anymore the physiologic lymphocyte traffic). Based on these observations, a 2-stage dissemination of MALT lymphomas could be postulated: one phase in which the disease first disseminates to other MALT sites and a second in which lymph node involvement occurs. The higher rate of multiple extranodal localizations in cases with nodal involvement appears in keeping with this hypothesis at least in a portion of cases. In this multicentric retrospective survey of cases observed over a long period of time, patients were treated according to the current policy of each institution at the time of diagnosis, and the presence of organ-specific problems presumably had a role in the choice of treatment. At a median follow-up of 3.4 years there was no evidence of a clear advantage for any type of therapy and, despite the high proportion of cases with disseminated disease, which should require a systemic approach, no clear advantage was associated with a chemotherapy program. In conclusion, as previously reported,46-48 nongastric MALT lymphomas, despite presenting with stage IV disease in approximately one fourth of cases, usually have a quite indolent course regardless of treatment type (5-year survival of 90%). The rate of histologic transformation seems much lower than in follicular lymphomas.49 Patients at high risk according to the IPI and those with lymph node involvement at presentation, but not those with involvement of multiple MALT sites, have a worse prognosis. Localization can be an important factor because of organ-specific problems, which result in particular management strategies. It seems that the incidence of the API2-MALT1 rearrangement or still unknown genetic lesions may be different at different sites.29,50 Whether different sites have a distinct natural history remains an open question; dissimilar prognostic variables at diagnosis might explain the observed differences (Table 6). In this IELSG series the patients with the disease initially presenting in the upper airways appeared to have a slightly poorer outcome (5-year OS, 46%), but their small number prevented any definitive conclusion. The optimal management of MALT lymphomas has not been yet clearly defined. Surgery, chemotherapy, and radiotherapy alone or in combination have been used. The treatment choice should be "patient-tailored," taking into account the site, the stage, and the clinical characteristics of the individual patient. Preliminary data support the activity of the anti-CD20 antibody rituximab in MALT lymphoma51 and the efficacy of its combination with chemotherapy needs to be explored.
The IELSG thanks all the investigators involved in the study (see "Appendix 1" and "Appendix 2") for their essential contribution, with each of them completely regarded as a coauthor of the present manuscript, and Cristina Morinini for her valuable assistance in data management.
Submitted April 30, 2002; accepted October 17, 2002.
Prepublished online as Blood First Edition Paper, November 27, 2002; DOI 10.1182/blood-2002-04-1279.
Supported in part by the Swiss Cancer League/Cancer Research Switzerland (grant no. SKL 652-2-1998).
E.Z. and A.C. contributed equally to this work.
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: Emanuele Zucca, International Extranodal Lymphoma Study Group, c/o Oncology Institute of Southern Switzerland, Ospedale San Giovanni, 6500 Bellinzona, Switzerland; e-mail: ielsg{at}ticino.com.
1.
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 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. Pathology & Genetics: Tumours of Haematopoietic and Lymphoid Tissues. World Health Organization Classification of Tumours. Lyon, France: IARC Press; 2001:157-160.
3.
The Non-Hodgkin's Lymphoma Classification Project.
A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma.
Blood.
1997;89:3909-3918
4.
Zucca E, Bertoni F, Roggero E, Cavalli F.
The gastric marginal zone B-cell lymphoma of MALT type.
Blood.
2000;96:410-419 5. Hyjek E, Isaacson PG. Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's thyroiditis. Hum Pathol. 1988;19:1315-1326[Medline] [Order article via Infotrieve]. 6. Hyjek E, Smith WJ, Isaacson PG. Primary B-cell lymphoma of salivary glands and its relationship to myoepithelial sialadenitis. Hum Pathol. 1988;19:766-776[Medline] [Order article via Infotrieve]. 7. Thieblemont C, Bastion Y, Berger F, et al. Mucosa-associated lymphoid tissue gastrointestinal and nongastrointestinal lymphoma behavior: analysis of 108 patients. J Clin Oncol. 1997;15:1624-1630[Abstract].
8.
Thieblemont C, Berger F, Dumontet C, et al.
Mucosa-associated lymphoid tissue lymphoma is a disseminated disease in one third of 158 patients analyzed.
Blood.
2000;95:802-806
9.
Zinzani P, Magagnoli M, Galieni P, et al.
Nongastrointestinal low-grade mucosa-associated lymphoid tissue lymphoma: analysis of 75 patients.
J Clin Oncol.
1999;17:1254-1258
10.
Zucca E, Roggero E, Bertoni F, Cavalli F.
Primary extranodal non-Hodgkin's lymphomas, part 1: gastrointestinal, cutaneous and genitourinary lymphomas.
Ann Oncol.
1997;8:727-737
11.
Zucca E, Roggero E, Bertoni F, Conconi A, Cavalli F.
Primary extranodal non-Hodgkin's lymphomas, part 2: head and neck, central nervous system and other less common sites.
Ann Oncol.
1999;10:1023-1033 12. Kaplan MA, Pettit CL, Zukerberg LR, Harris NL. Primary lymphoma of the trachea with morphologic and immunophenotypic characteristics of low-grade B-cell lymphoma mucosa-associated lymphoid tissue. Am J Surg Pathol. 1992;16:71-75[Medline] [Order article via Infotrieve]. 13. Nicholson AG, Wotherspoon AC, Diss TC, et al. Pulmonary B-cell non-Hodgkin's lymphomas: the value of immunohistochemistry and gene analysis in diagnosis. Histopathology. 1995;26:395-403[Medline] [Order article via Infotrieve]. 14. Isaacson PG, Chan JKC, Tang C, Addis BJ. Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue arising in the thymus: a thymic lymphoma mimicking myoepithelial sialadenitis. Am J Surg Pathol. 1990;14:342-351[Medline] [Order article via Infotrieve]. 15. Mattia AR, Ferry JA, Harris NL. Breast lymphoma: a B-cell spectrum including the low grade B-cell lymphoma of mucosa associated lymphoid tissue. Am J Surg Pathol. 1993;17:574-587[Medline] [Order article via Infotrieve]. 16. Bailey EM, Ferry JA, Harris NL, Mihm MC Jr, Jacobson JO, Duncan LM. Marginal zone lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type) of skin and subcutaneous tissue. Am J Surg Pathol. 1996;20:1011-1023[CrossRef][Medline] [Order article via Infotrieve]. 17. Isaacson PG, Banks PM, Best PV, McLure SP, Muller-Hermelink HK, Wyatt JI. Primary low-grade hepatic B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)-type. Am J Surg Pathol. 1995;19:571-575[Medline] [Order article via Infotrieve]. 18. Wotherspoon AC, Hardman-Lea S, Isaacson PG. Mucosa-associated lymphoid tissue (MALT) in the human conjunctiva. J Pathol. 1994;174:33-37[CrossRef][Medline] [Order article via Infotrieve]. 19. Parveen T, Navarro-Roman L, Medeiros LJ, Raffeld M, Jaffe ES. Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue arising in the kidney. Arch Pathol Lab Med. 1993;117:780-783[Medline] [Order article via Infotrieve]. 20. Kumar S, Kumar D, Kaldjian EP, Bauserman S, Raffeld M, Jaffe ES. Primary low-grade B-cell lymphoma of the dura: a mucosa associated lymphoid tissue-type lymphoma. Am J Surg Pathol. 1997;21:81-87[CrossRef][Medline] [Order article via Infotrieve].
21.
Du MQ, Xu CF, Diss TC, et al.
Intestinal dissemination of gastric mucosa-associated lymphoid tissue lymphoma.
Blood.
1996;88:4445-4451
22.
Du MQ, Peng HZ, Dogan A, et al.
Preferential dissemination of B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma to the splenic marginal zone.
Blood.
1997;90:4071-4077 23. Drillenburg P, van der Voort R, Koopman G, et al. Preferential expression of the mucosal homing receptor integrin alpha 4 beta 7 in gastrointestinal non-Hodgkin's lymphomas. Am J Pathol. 1997;150:919-927[Abstract]. 24. Dogan A, Du M, Koulis A, Briskin M, Isaacson P. Expression of lymphocyte homing receptors and vascular addressing in low-grade gastric B-cell lymphomas of mucosa-associated lymphoid tissue. Am J Pathol. 1997;151:1361-1369[Abstract].
25.
Drillenburg P, Pals ST.
Cell adhesion receptors in lymphoma dissemination.
Blood.
2000;95:1900-1910
26.
Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M.
Report of the Committee on Hodgkin's Disease Staging Classification.
Cancer Res.
1971;31:1860-1861
27.
The International Non-Hodgkin's Lymphoma Prognostic Factors Project.
A predictive model for aggressive non-Hodgkin's lymphoma.
N Engl J Med.
1993;329:987-994 28. Zucca E, Conconi A, Roggero E, et al. Non-gastric MALT lymphomas: a survey of 369 European patients. The International Extranodal Lymphoma Study Group [abstract]. Ann Oncol. 2000;11:99. 29. Cavalli F, Isaacson PG, Gascoyne RD, Zucca E. MALT lymphomas Hematology (American Society of Hematology Education Program).; 2001:241-258.
30.
Cheson BD, Horning SJ, Coiffier B, et al.
Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas.
J Clin Oncol.
1999;17:1244-1253 31. Altman DG, De Stavola BL, Love SB, Stepniewska KA. Review of survival analyses published in cancer journals. Br J Cancer. 1995;72:511-518[Medline] [Order article via Infotrieve]. 32. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457-481[CrossRef]. 33. Cox DR. Regression models and life tables. J R Stat Soc. 1972;34:187-220. 34. Roggero E, Zucca E, Mainetti C, et al. Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin. Hum Pathol. 2000;31:263-268[CrossRef][Medline] [Order article via Infotrieve].
35.
Isaacson P.
Gastric MALT lymphoma: from concept to cure.
Ann Oncol.
1999;10:637-645 36. Isaacson P. Mucosa-associated lymphoid tissue lymphoma. Semin Hematol. 1999;36:139-147[Medline] [Order article via Infotrieve].
37.
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 38. Jonsson V, Wiik A, Hou-Jensen K, et al. Autoimmunity and extranodal lymphocytic infiltrates in lymphoproliferative disorders. J Intern Med. 1999;245:277-286[CrossRef][Medline] [Order article via Infotrieve]. 39. Cortelazzo S, Rossi A, Roggero E, et al. Treatment outcome and prognostic factors in patients with localized primary gastrointestinal (gi) diffuse large cell lymphoma [abstract]. Blood. 1999;94:599a.
40.
Royer B, Cazals-Hatem D, Sibilia J, et al.
Lymphomas in patients with Sjögren's syndrome are marginal zone B-cell neoplasms, arise in diverse extranodal and nodal sites, and are not associated with viruses.
Blood.
1997;90:766-775 41. Aceti A, Talianai G, Sorice M, Amendolea MA. HCV and Sjögren's syndrome. Lancet. 1992;339:1425-1426[Medline] [Order article via Infotrieve].
42.
Miklos JA, Swerdlow SH, Bahler DW.
Salivary gland mucosa-associated lymphoid tissue lymphoma immunoglobulin V(H) genes show frequent use of V1-69 with distinctive CDR3 features.
Blood.
2000;95:3878-3884
43.
Marasca R, Vaccari P, Luppi M, et al.
Immunoglobulin gene mutations and frequent use of VH1-69 and VH4-34 segments in hepatitis C virus-positive and hepatitis C virus-negative nodal marginal zone B-cell lymphoma.
Am J Pathol.
2001;159:253-261
44.
Chan CH, Hadlock KG, Foung SK, Levy S.
V(H)1-69 gene is preferentially used by hepatitis C virus-associated B cell lymphomas and by normal B cells responding to the E2 viral antigen.
Blood.
2001;97:1023-1026 45. Ferreri AJ, Freschi M, Dell'Oro S, Viale E, Villa E, Ponzoni M. Prognostic significance of the histopathologic recognition of low- and high-grade components in stage I-II B-cell gastric lymphomas. Am J Surg Pathol. 2001;25:95-102[Medline] [Order article via Infotrieve]. 46. Raderer M, Vorbeck F, Formanek M, et al. Importance of extensive staging in patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma. Br J Cancer. 2000;83:454-457[CrossRef][Medline] [Order article via Infotrieve].
47.
Sancho JM, Ribera JM, Vaquero M, Oriol A, Hernandez-Rivas JA, Feliu E.
Non-gastrointestinal malt lymphomas: a study of 10 cases and comparison with 27 patients with gastrointestinal MALT lymphoma.
Haematologica.
2000;85:557-559 48. Ferrer A, Lopez-Guillermo A, Bosch F, et al. Non-gastric mucosa-associated lymphoid tissue (MALT) lymphomas: analysis of 14 patients [in Spanish]. Med Clin (Barc). 1999;112:577-580[Medline] [Order article via Infotrieve]. 49. Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin's lymphomas. N Engl J Med. 1984;311:1471-1475[Abstract].
50.
Remstein ED, Kurtin PJ, James CD, Wang XY, Meyer RG, Dewald GW.
Mucosa-associated lymphoid tissue lymphomas with t(11;18)(q21;q21) mucosa-associated lymphoid tissue lymphomas with aneuploidy develop along different pathogenetic pathways.
Am J Pathol.
2002;161:63-71 51. Conconi A, Thieblemont C, Martinelli G, et al. Activity of rituximab in extranodal marginal-zone lymphomas (MALT-type) [abstract]. Blood. 2001;98:807a.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Top
Abstract
Introduction
2-microglobulin levels, hepatitis C virus (HCV)
infection serology, and association with previous autoimmune
disease. The distribution among the International Prognostic Index
(IPI) risk groups was defined according to the published
criteria.
2 test was used for testing associations in 2-way
tables. The Cox proportional hazards model was used for
multivariate analysis of OS, CSS, and PFS and estimation of relative
risk.
