What is the recommended treatment for an adult male with low‑grade marginal‑zone B‑cell lymphoma involving the bone marrow, marked reduction of normal hematopoietic cells, mild fibrosis, and cytopenias?

Treatment of Low-Grade Marginal Zone B-Cell Lymphoma with Extensive Bone Marrow Involvement and Cytopenias

For this adult male with marginal zone lymphoma involving 90% of bone marrow with marked reduction of hematopoietic cells and cytopenias, rituximab monotherapy (375 mg/m² for 4-8 weekly doses) is the recommended first-line treatment, as it produces high response rates (>80%) with minimal toxicity and can rapidly restore cytopenias without the surgical risks of splenectomy. 1

Initial Treatment Approach

Rituximab as First-Line Therapy

• Rituximab monotherapy is the preferred initial treatment for patients with symptomatic marginal zone lymphoma and cytopenias, producing overall response rates exceeding 80% and complete response rates above 40% with rapid hematologic improvement 1

• The standard dosing is 375 mg/m² administered weekly for 4-8 doses, with responses typically being long-lasting (10-year progression-free survival exceeding 60%) 1

• Rituximab should only be administered by healthcare professionals with appropriate medical support to manage severe infusion-related reactions, with mandatory premedication before each infusion 2

• Screen for hepatitis B virus (HBsAg and anti-HBc) before initiating rituximab, as HBV reactivation can occur and result in fulminant hepatitis, hepatic failure, and death 2

Alternative to Splenectomy

• While splenectomy was traditionally considered first-line treatment for splenic marginal zone lymphoma with cytopenias (producing 5-year progression-free survival of 50-60%), it has been largely replaced by rituximab due to the risk of severe and potentially fatal acute and late complications 1

• Splenectomy cannot completely eradicate disease and is now reserved for specific situations where medical therapy has failed 1

Maintenance and Combination Therapy Considerations

Rituximab Maintenance

• Maintenance rituximab (every 2 months for 1-2 years) may improve progression-free survival after initial response to induction therapy 1

Combination Chemoimmunotherapy

• For patients with more aggressive disease features or those requiring more intensive therapy, rituximab plus bendamustine (BR) is the recommended first-line combination for marginal zone lymphoma, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma 1

• A study of 13 patients with Sjögren syndrome-associated marginal zone lymphoma (77% stage IV) showed BR combination achieved efficacy in all cases with good safety profile 1

• Rituximab plus fludarabine is an alternative combination regimen for marginal zone lymphoma 1

Critical Pre-Treatment Workup

Mandatory Assessments

• Complete blood counts with differential and platelet counts must be obtained prior to each rituximab dose to monitor cytopenias 2

• Hepatitis C virus serology (with HCV-RNA PCR and genotyping if positive) is mandatory, as HCV is associated with marginal zone lymphoma 1

• Hepatitis B virus markers and HIV serology are required before treatment initiation 1

• Serum and urine immunofixation, protein electrophoresis, lactate dehydrogenase, and β2-microglobulin should be measured 1

Diagnostic Confirmation

• MYD88 mutation testing is suggested to exclude lymphoplasmacytic lymphoma, as MYD88 mutations are detected in the majority of lymphoplasmacytic lymphomas but are rare in marginal zone lymphomas 1

• The CD20+, PAX-5+, BCL-2+, CD23+ immunophenotype with CD10 negativity is consistent with marginal zone lymphoma 1

Monitoring During Treatment

Response Assessment

• Monitor complete blood counts including platelets prior to each rituximab course during monotherapy 2

• Clinical examination should assess for resolution of cytopenias (hemoglobin >12 g/dL, platelets >100×10⁹/L, neutrophils >1.5×10⁹/L) and reduction in bone marrow infiltration 1

• Flow cytometry should demonstrate absence of circulating clonal B cells (light chain-restricted B cells) for complete response 1

• Bone marrow biopsy with immunohistochemistry should show no evidence of infiltration for complete response 1

Common Pitfalls and Caveats

Infusion-Related Reactions

• Approximately 80% of fatal infusion reactions occur with the first rituximab infusion, requiring close monitoring and immediate availability of resuscitation equipment 2

• Discontinue rituximab for severe reactions and provide medical treatment for Grade 3 or 4 infusion-related reactions 2

Differential Diagnosis Considerations

• The presence of CD23 positivity (as in this case) can occur in marginal zone lymphoma and does not exclude the diagnosis 1

• Paratrabecular involvement would favor lymphoplasmacytic lymphoma over marginal zone lymphoma, but this feature is not described in this case 3

• The extensive bone marrow involvement (90%) with marked reduction of hematopoietic cells indicates need for treatment rather than watchful waiting 1

Post-Treatment Monitoring

• When interpreting post-rituximab bone marrow biopsies, use CD79a antibody rather than CD20, as rituximab treatment may lead to false-negative interpretations of residual B-cell disease 4

• Progressive multifocal leukoencephalopathy (PML), including fatal PML, can occur in patients receiving rituximab and requires vigilance for neurologic symptoms 2

Watch-and-Wait Not Appropriate

• While watchful waiting may be considered for low-grade lymphomas confined to exocrine glands without constitutional symptoms, this patient's extensive bone marrow involvement (90%) with marked reduction of hematopoietic cells and cytopenias constitutes an indication for immediate treatment 1

• The presence of cytopenias and near-complete replacement of normal hematopoiesis represents high disease burden requiring active intervention 1