What is the initial treatment approach for a patient with Non-Hodgkin's Lymphoma (NHL) of the spleen?

Initial Treatment Approach for Non-Hodgkin's Lymphoma of the Spleen

For NHL involving the spleen, treatment is determined by whether disease is truly isolated to the spleen/splenic hilum (extremely rare) versus systemic disease with splenic involvement, with the latter requiring systemic chemotherapy based on histologic subtype and stage.

Diagnostic Workup and Staging

Before initiating treatment, complete staging is essential to distinguish isolated splenic disease from systemic involvement:

• PET-CT is the preferred imaging modality for staging FDG-avid NHL subtypes, as it is more sensitive than CT alone for detecting nodal and extranodal disease sites 1
• Contrast-enhanced CT of chest, abdomen, and pelvis is mandatory if PET-CT is unavailable or for non-FDG-avid histologies 1
• Bone marrow biopsy can be omitted if PET-CT is performed and shows no bone/marrow involvement in DLBCL, as PET-CT is more sensitive (94% detection rate vs 40% for biopsy) 1
• For indolent lymphomas with clinical stage III disease, bone marrow biopsy may be deferred if observation is planned, but is essential for evaluating potentially early-stage (I-II) disease 1
• Laboratory evaluation must include complete blood count, LDH, comprehensive metabolic panel, and screening for hepatitis B, hepatitis C, and HIV 1, 2

Treatment Based on Disease Extent

True Primary Splenic Lymphoma (Spleen + Splenic Hilum Only)

This presentation is exceedingly uncommon, representing isolated stage I disease 3:

• Splenectomy followed by observation or abbreviated chemotherapy may be appropriate, as pathologically staged primary splenic NHL has favorable prognosis approximating limited-stage NHL at other sites 3
• Consider 2-4 cycles of systemic chemotherapy based on histologic subtype even for isolated disease, given the systemic nature of most NHL 2

Systemic NHL with Splenic Involvement (Stage III-IV)

This is the typical presentation, as the spleen is considered nodal tissue and involvement indicates advanced disease 1:

For Diffuse Large B-Cell Lymphoma (most common aggressive NHL):

• Six to eight cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) every 21 days is standard treatment for CD20-positive disease 2
• R-CHOP-14 (every 14 days) may be considered in selected patients 2
• Treatment stratification should be based on International Prognostic Index (IPI) score 2

For Indolent B-Cell NHL (follicular, marginal zone):

• Bendamustine 120 mg/m² IV on days 1 and 2 of a 21-day cycle for up to 8 cycles is FDA-approved for indolent NHL that has progressed during or within 6 months of rituximab-containing therapy 4
• Alternative regimens include R-CHOP or R-CVP (rituximab, cyclophosphamide, vincristine, prednisone) 1
• Observation ("watch and wait") is appropriate for asymptomatic, low-burden follicular lymphoma even with splenic involvement 1

For Mantle Cell Lymphoma:

• R-hyper-CVAD (rituximab with fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate and cytarabine) is preferred for younger patients (<65 years) 1
• R-CHOP or R-bendamustine are alternatives for older patients or those unable to tolerate intensive therapy 1
• Endoscopy/colonoscopy is necessary to confirm stage I-II disease and assess response, given the 88-92% rate of GI involvement in MCL 1

Critical Treatment Considerations

Dose Modifications for Bendamustine

If using bendamustine for indolent NHL 4:

• Delay treatment for Grade 4 hematologic toxicity or clinically significant ≥Grade 2 non-hematologic toxicity
• Reduce to 90 mg/m² for Grade 4 hematologic toxicity; further reduce to 60 mg/m² if toxicity recurs
• Reduce to 90 mg/m² for Grade 3+ non-hematologic toxicity; further reduce to 60 mg/m² if toxicity recurs

Role of Radiotherapy

• Radiotherapy has limited role in splenic NHL and is not part of standard treatment for systemic disease 5
• Involved-field radiotherapy may be considered only for truly localized stage I disease after splenectomy, similar to other localized NHL sites 5
• Palliative radiotherapy remains an option for symptomatic bulky masses regardless of subtype 5

Common Pitfalls to Avoid

• Do not assume isolated splenic disease without complete staging, as most splenic NHL represents systemic involvement requiring systemic therapy 1, 3
• Do not perform routine bone marrow biopsy if PET-CT is available for DLBCL staging, as it rarely changes management 1
• Do not use bendamustine in patients with creatinine clearance <30 mL/min 4
• Monitor for tumor lysis syndrome in patients with high tumor burden, particularly with aggressive histologies 4
• Screen for hepatitis B reactivation before and during rituximab-containing therapy 2