Page 1437 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 79 Marginal Zone Lymphomas (Extranodal/Malt, Splenic, and Nodal) 1283

prednisone) and R-CNOP (rituximab, cyclophosphamide, mitoxan- Suggested Treatment Approach to Extranodal Marginal Zone Lymphoma
161
trone [Novantrone], vincristine [Oncovin], and prednisone). These
regimens have mostly been used in patients who were believed to Stage I/II
have more aggressive disease. CR rates vary from 61% to 100%, with Gastric H. pylori–Positive
relapse rates reaching up to 36% on long-term follow-up. Advanced/
transformed IPSID has usually been treated with combination che- • Antibiotic therapy
motherapy, such as CHOP. 7,162 • Repeat endoscopy in 3–6 months
• If still H. Pylori–positive and no progression, alternative antibiotic
therapy
• Repeat endoscopy in 3 months
Radioimmunotherapy
Nongastric, Gastric H. pylori–Negative or Not Responding to Antibiotic
Radioisotope-conjugated forms of anti-CD20 antibodies (ibritu- Therapy
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momab and tositumomab) have also been used both as first-line • Antibiotic trial for stage I gastric, ocular, or cutaneous?
therapy (eight CRs and one PR in nine patients with ocular adnexal • Involved field radiation therapy (30 Gy)
ENMZL) and for relapsed disease 164,165 (three CRs and three PRs in Stage III/IV or Relapsed After Antibiotic and Radiation Therapy
six patients with ocular adnexal ENMZL; four CRs and one PR in • Expectant observation until indication to treat
six patients with a variety of primary sites). The combination of • Rituximab ± single-agent alkylator/purine analogue or
conventional radiation therapy and rituximab has been studied for combination chemotherapy (CVP/FND)
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early-stage follicular lymphoma. There are no published studies of
its use on ENMZL.
The recent explosion of genomic analysis of these neoplasms has
also led to a plethora of findings that have been shown to have
Therapy for Relapsed Disease prognostic significance in ENMZL. For instance, the expression of
FOXP1 in tumors predicts poor prognosis and transformation to
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Limited relapses can be retreated, if feasible, with local therapy. diffuse large B-cell lymphoma. Although these findings are not yet
Otherwise, treatment considerations are similar to those described for incorporated into clinical practice, as they become more widely avail-
advanced disease. Symptomatic, relapsed extensive disease will usually able, they may be useful for risk stratification and therapeutic deci-
require an alternative regimen to those previously used. sions (see box on Suggested Treatment Approach to Extranodal
The role of hematopoietic stem cell transplantation is controversial Marginal Zone Lymphoma).
because most series do not directly address ENMZL and thus most
recommendations are again extrapolated from studies of FL. 167–171
Given that most young patients with relapsed systemic ENMZL are SPLENIC MARGINAL ZONE LYMPHOMA
likely to succumb to complications of their disease, considering them
for allogeneic stem cell transplantation is reasonable, although this Epidemiology and Manifestations
should preferably take place on a clinical trial. Encouraging results
have also recently been reported with high-dose therapy and autolo- SMZL (Fig. 79.3; E-Slide VM03955) is a rare disease, corresponding
8
gous stem cell transplantation specifically for MZL. 172 to <1% of all NHL, with a yearly incidence rate of 0.25 per 100,000
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adults in the United States according to SEER data. The median
age at diagnosis is around 65, but as with ENMZL, the age range
Prognosis is wide and there may be a slight female predominance. The vast
majority of patients present with advanced-stage disease involving the
Overall, prognosis of limited stage ENMZL is excellent, as mentioned spleen (with splenomegaly in more than 80% of patients), abdominal
in each of the treatment subsections. Even for advanced disease, (mainly splenic hilar) lymph nodes, and in 83%–94% of patients, the
the expected lymphoma-specific survival at 5 years is close to 90%, bone marrow. 178–181 Peripheral lymphadenopathy is, however, uncom-
with some series showing survivals similar to those of early disease. mon. Liver involvement is seen in up to one-fourth of patients, and
A recent retrospective analysis of SEER data lists the best 5-year rarely other nonhematopoietic sites can also be involved. B symptoms
overall survivals for cutaneous (88%), ocular (83%) and thyroid occur in approximately 25%–60% of patients, depending on the
(85%) forms, and worst for genitourinary (76%), intestinal (69%), series. 179,180
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and central nervous system (71%) forms. As in other indolent Circulating villous lymphocytes (with short polar villi) can be seen
lymphomas, transformation to aggressive forms (DLBCL) can occur, in approximately two-thirds of patients (see Fig. 79.3B) and frank
but this is thought to be a rare event (less than 10% of cases) lymphocytosis in up to one-half. This has led to a prior designation
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associated with acquisition of additional genetic abnormalities. of splenic lymphoma with villous lymphocytes being given to a specific
Regardless, even patients in CR after first-line therapy can develop presentation of this disorder and explains why the disease was called
DLBCL. For instance, 0.05% of individuals with gastric ENMZL SMZL with or without villous lymphocytes in a previous version of the
who underwent successful antibiotic treatment had evidence of WHO classification. Anemia is seen in about one-half to two-thirds
88
DLBCL between 6 months and 2 years after achieving remission. and thrombocytopenia in one-fifth of cases, which can be the result
On the other hand, untreated IPSID tends to evolve to large-cell of bone marrow involvement or an autoimmune process (seen in
transformation. 7,162 approximately 15% of patients). Between 25% and 40% of patients
As for other lymphomas, the International Prognostic Index have a low-level circulating monoclonal immunoglobulin (mostly
180
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(IPI) (see Chapter 82) predicts outcomes, with reported 5-year IgM), and in a few patients, especially in those with active hepatitis
overall survivals of >90%, 70%–80%, and 40%–50% for patients C virus (HCV) infection, mixed cryoglobulins can be demonstrated,
with low, low-intermediate/high-intermediate, and high-risk scores, which can be associated with vasculitis. 182,183
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respectively. Nonetheless, the utility of the IPI in ENMZL has been
174
disputed. One of the main criticisms to its use in patients with
indolent lymphomas is that prognostic subgroups do not have a good Pathobiology and Differential Diagnosis
discriminating power, because most patients are assigned to the favor-
able outcome groups and only very few patients are allocated to the Etiology
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adverse prognostic groups. To circumvent this issue, modifications
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of the original IPI have been proposed in some cases, but none has Approximately 10%–20% of SMZL patients from European series
been universally adopted. have evidence of HCV infection, 178,181 and a significant fraction of