Page 1435 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 79 Marginal Zone Lymphomas (Extranodal/Malt, Splenic, and Nodal) 1281

with an appropriate test, such as the urea breath test, at least 4 for H. pylori were seen. Whether most complete remissions equate
weeks after finishing antibiotherapy and 2 weeks after discontinuing to cures is a question that will require longer follow-up studies.
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PPI. Pooled data from several prospective and retrospective studies An additional argument in favor of periodic endoscopies is that
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suggest more than 90% eradication rates after initial antibiotherapy. H. pylori may be associated with an increased risk for gastric
Persistent infection should be treated with a different course of adenocarcinoma. 121
antibiotics, preferably guided by sensitivity tests, because the same Molecular studies should not be done routinely in follow-up
data suggest an eradication rate close to 100% after second- or biopsy samples, outside of a research protocol. Several studies have
third-line treatments. Repeat endoscopy with biopsies should be shown that molecular disease, defined by the presence of residual
obtained 3 months after completion of antibacterial therapy to t(11;18) or monoclonal immunoglobulin as evidenced by PCR
assess tumor response and also to allow histologic confirmation of methods, may still be detected even with complete pathologic
H. pylori eradication. If H. pylori is still detected, a different antibiotic remissions. 100,122,123 However, this finding is not associated with an
combination should be tried and the patient reassessed as mentioned increased relapse rate and thus is not currently helpful for clinical
previously. 9,11 management.
Responses to therapy are classified according to biopsy findings on
endoscopy. Complete histologic response (complete remission [CR])
should be confirmed by a second endoscopy 3 months later and is Ocular Extranodal Marginal Zone Lymphoma
managed by observation and regular follow up thereafter as clinically
indicated. The presence of small residual lymphoid aggregates early Localized forms of ocular adnexal ENMZL are most frequently
after H. pylori eradication, corresponding to a category of prob- managed with radiation therapy, with treatment specifics dependent
able minimal residual disease in the French Study Group of Adult on the exact location of the tumor in the orbit. Reported responses
Lymphomas (GELA) grading system for posttreatment evaluation, are very good, with CR rates of 83%–100%. 124–133 Local recurrence
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should also be managed as CR. In some cases, these lymphoid rates vary between 0% and 17%, and distant recurrences can occur
aggregates have been shown to harbor cells with the same monoclonal up to 25% over 10 years, although disease-specific survival approaches
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rearrangements of the original tumor. Nevertheless, these patients 100% in most series. The exact site of presentation correlates with
do not seem to have an increased risk for relapse and most will have the risk for systemic recurrence, the lowest being for conjunctival and
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evidence of complete response in a subsequent evaluation. 87 the highest for eyelid primaries. Long-term complications, such as
Patients with overt residual (partial remission [PR]) or stable cataract formation and xerophthalmia, occur in approximately half
disease, as long as asymptomatic, can also be managed conservatively, the patients. 134
with observation or antibiotherapy as appropriate, for several months. Based on the success of antibiotherapy for H. pylori–associated
Of interest, responses may occur as late as more than 18 months ENMZL and reports of the presence of Chlamydophila psittaci (by
after completion of antibiotic therapy. 43,87 Progressive or symptomatic PCR, immunofluorescence, or electron microscopy) in ocular tissues
disease should be managed with local therapy, with radiotherapy of patients affected by ocular adnexal ENMZL, a course of an anti-
being preferred. Despite its established efficacy in disease control, chlamydial antibiotic has been evaluated as initial management for
gastrectomy, because of its immediate morbidity and long-term these patients. 45–55 A few of these studies have reported PR or CR in
metabolic complications, is currently reserved for management of a significant fraction of these patients, with a recent prospective study
rare complications such as perforation or bleeding that cannot be documenting an overall response rate (CR+PR) of 65% and suggest-
controlled endoscopically. 9,11 ing improved response rate and progression-free survival in patients
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A recent meta-analysis of 1436 patients with early stage (IE-IIE1) in whom C. psittaci eradication was documented. However, the
H. pylori–positive disease on prospective or retrospective studies recommendation to treat with a tetracycline at initial diagnosis is still
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estimates an overall CR rate of 78% after eradication of H. pylori, controversial because the reported rates of association with C. psittaci
but with individual study remission rates anywhere from 47% to are highly variable—some studies suggest prevalences as high as 80%,
100%. 15,17,41–43,86,89–113 On univariate analysis of available data from whereas others are not able to detect the organism in any of the
the same studies, adverse risk factors for achieving remission included patients. A meta-analysis has suggested that the benefit of antibio-
the presence of t(11;18), stage greater than IE1, proximal (body or therapy may be restricted to specific geographic areas and, even then,
fundus) location of lesions, and Western (versus Asian) residence. is likely to be limited. 135
No good evidence is available to support adjuvant chemotherapy
after anti–H. pylori treatment as a means to prevent recurrence in
localized gastric MALT lymphomas, although this has only been Cutaneous Extranodal Marginal Zone Lymphoma
formally addressed with an additional single agent (chlorambucil). 114
The management of early-stage H. pylori–negative disease is Results for both surgical excision and radiation therapy for limited
controversial, with some groups suggesting involved field radiation disease are comparable, with CR rates approaching 100%. Both
therapy or, if radiation therapy is contraindicated, systemic therapy approaches have a relapse rate (usually limited to the skin) of around
9
with rituximab as initial treatment, whereas others propose a trial 45%. Encouraging results have also been obtained with intralesional
11
of anti-Helicobacter therapy. The rationale for the latter derives injection of rituximab or α-interferon. 38
from anecdotal reports of CR in H. pylori–negative gastric ENMZL Studies from Europe have suggested an association between Bor-
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patients who were treated exclusively with antibacterials, with relia burgdorferi infection and ENMZL of the skin, although this has
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a metaanalysis suggesting a response rate of up to 19%. These not been reproduced in Asian and American studies. 56–59 In view of
patients are assumed to have been infected with H. pylori that was this, similar to ocular lymphoma, it has been suggested that a course
missed by diagnostic tests or with a different species of Helicobacter, of a tetracycline may be a reasonable first approach, especially in
several of which have been recently recognized. 117,118 locations where the association has been documented or when infec-
Responses to radiation therapy are excellent, with some series tion by B. burgdorferi is detected.
reporting CR rates of up to 100% with total doses as low as
30 Gy. 119,120 Recurrence rate is very low in these patients, but follow
up is limited for most series reported. IPSID
The optimal follow-up schedule is unknown, although most
recommend periodic endoscopies every 3–6 months for the first 5 Antibiotherapy (varying from single-agent tetracycline to triple-
years and yearly thereafter. 9,11 Long-term follow-up data in patients antibiotic therapy with ampicillin, metronidazole, and tetracycline,
with complete remission after H. pylori eradication document a 7.2% or an H. pylori regimen) 136–139 has long been recognized as being able
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relapse rate overall (2.2% per year). Some of these relapses were to induce CR in early-stage disease. Recently, IPSID has been associ-
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associated with H. pylori recurrence, and responses to retreatment ated with chronic infection with Campylobacter jejuni. Therefore