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Chapter 79 Marginal Zone Lymphomas (Extranodal/Malt, Splenic, and Nodal) 1285

with IFN-α had a relapse of the lymphoma with detectable levels of Suggested Treatment Approach to Splenic Marginal Zone Lymphoma
HCV RNA; treatment with IFN-α and ribavirin resulted in second
complete virologic and hematologic responses. Given that newer HCV-Positive
anti-HCV drugs are less toxic and more effective than IFN-α, these • Anti-HCV therapy
may become first choice for these patients. Of note, evidence of
monoclonal immunoglobulin gene rearrangement may persist after HCV-Negative (or Not Responding to Anti-HCV Therapy) or Relapsed
successful treatment of HCV and SMZL. 183 • Expectant observation until indication to treat
• Rituximab
• Splenectomy?
Rituximab • Rituximab + single-agent alkylator/purine analogue or
combination chemotherapy (CVP/FND)
• If contraindication to splenectomy and systemic therapy, low-dose
Rituximab has been used as single agent or in combination with splenic irradiation
chemotherapeutic drugs in symptomatic HCV-negative patients or
in those whose disease did not respond to anti-HCV treatment. The
response rate to single-agent rituximab in a retrospective subseries of
25 patients with splenic and nonsplenic MZL was 88%, which
compared favorably with that of 11 patients who received chemo-
196
therapy alone (55%). In two other retrospective studies, rituximab low-dose radiation (around 4 Gy) can result in resolution of spleno-
208
was found to be an effective therapy in 90%–95% patients with megaly and correction of cytopenias, at least temporarily.
SMZL, with reduction in splenomegaly and improvement in blood Although it is tempting to compare the results of observation,
counts. 197,198 Because of its low toxicity, single agent rituximab is often splenectomy and systemic therapy, this is not prudent. All published
proposed as initial therapy for symptomatic SMZL. series have considerable selection bias, because patients who are
believed to have more aggressive disease have been usually offered
more-intensive therapies.
Splenectomy
Before rituximab was widely available and studied in SMZL, Prognosis
splenectomy was frequently used as first-line therapy. A benefit
of this procedure, which may be done for diagnostic purposes Reported 5-year overall survival rates vary from 65%–78%, 180,194 with
10
in patients with localized disease, is the usual improvement of a median survival of 10.4 years. The Italian Lymphoma Intergroup
cytopenias occurring as a result of hypersplenism. Precise response (ILI) has proposed a prognostic model using hemoglobin less than
rates to splenectomy are difficult to ascertain. All of 25 patients in 12 g/dL, LDH higher than normal, and albumin less than 3.5 g/dL
178
a series treated with splenectomy alone had responses, including as risk factors. Low-risk (no factors), intermediate-risk (one factor),
10
two CRs. Most responses were durable: only eight of these 25 and high-risk (two or more factors) patients have 5-year overall sur-
patients experienced disease progression on long-term follow up, vivals of 83%, 72%, and 56%, respectively. Shorter survival has been
with a median time to progression of 32 months (with a range of associated with CD38 expression, unmutated variable region immu-
199
4–137 months). Moreover, all of 16 patients treated with first-line noglobulin genes, and expression of a specific set of NFκB pathway
188
splenectomy in an earlier series had good responses, most likely genes (by gene expression array). The presence of both del(8p) and
partial (complete responses could not be assessed because of a lack del(17p) involving TP53 is associated with worse prognosis, although
77
of bone marrow assessment after treatment); two patients progressed isolated deletion 17p is not. Transformation to aggressive lymphoma
10
195
subsequently. Finally, another series of 28 patients documented may occur in around 10% of cases (see box on Suggested Treatment
a 5-year overall survival of 71% after splenectomy; no CRs were Approach to SMZL).
194
reported. Although an effective procedure with very low operative
mortality, splenectomy is associated with a long-term increased risk
of infection and sepsis, and possibly a hypercoagulable state with
200
potential cardiovascular complications. On the other hand, retro- NODAL MARGINAL ZONE LYMPHOMA
spective analysis of SEER data showed no advantage of splenectomy
201
over other treatment approaches for SMZL. Given these consid- Epidemiology and Manifestations
erations, the role of therapeutic splenectomy in SMZL has been
questioned. 202,203 NMZL represents approximately 2% of all NHL, corresponding to
a yearly incidence rate of 0.83 per 100,000 adults in the United States
according to SEER data. The reported incidence of NMZL has
Chemotherapy increased significantly over the previous decade, but it is unclear
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whether this is the result of a true increase in the number of cases or
Single alkylating agents (chlorambucil or cyclophosphamide) have of an increased recognition of this entity. The diagnosis requires the
also been used for treatment of SMZL. Most series are very small, absence of extranodal or splenic disease, the presence of which makes
but all report a significant fraction of responses, albeit mostly partial. ENMZL and SMZL more likely. The median age at presentation is
Fludarabine has produced encouraging results also, 204,205 but the around 60, and in most series there is a slight female predominance.
efficacy of cladribine is controversial. 206,207 The use of combination Most patients present with asymptomatic lymphadenopathy, most
chemotherapy (including CVP and CHOP) has also been reported, often in peripheral lymph nodes (especially cervical and inguinal),
but differences between CHOP (or CHOP-like) therapy and other which is frequently associated with mediastinal or abdominal involve-
180
less-intensive regimens could not be demonstrated. In a subseries ment. The most recent series report the presence of B symptoms in
of 19 patients treated with chemotherapy alone, the 5-year overall less than 20% of patients. 32,179,209–213 Except in three of the published
survival rate was 64%. 194 series, 210–212 the majority of patients present with stage III or IV
disease (approximately 70%–80% of cases), with bone marrow
involvement detected in up to two-thirds of cases. Anemia and
Radiation Therapy thrombocytopenia have been described in up to 30% and 10% of
cases, respectively. A monoclonal IgM is seen in approximately 10%
In patients ineligible for any of the aforementioned therapies, radia- of patients. A pediatric form, with excellent prognosis, has been
tion therapy to the spleen can be used for symptomatic control. Even recognized, reported in 2003. 214