What is the recommended treatment for a patient with stage three disease with spleen involvement?

R-CHOP is the Standard First-Line Treatment for Stage III Diffuse Large B-Cell Lymphoma with Splenic Involvement

For patients with stage III diffuse large B-cell lymphoma (DLBCL) with splenic involvement, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) is the recommended first-line treatment regimen. 1

Treatment Regimen Details

R-CHOP consists of:

• Rituximab 375 mg/m² IV on day 1
• Cyclophosphamide 750 mg/m² IV on day 1
• Doxorubicin 50 mg/m² IV on day 1
• Vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1
• Prednisone 100 mg/day orally for 5 days
• Administered every 21 days for 6-8 cycles

Evidence Supporting R-CHOP

The Italian Society of Hematology guidelines explicitly recommend that patients with stage III-IV DLBCL should receive anthracycline-containing chemotherapy with rituximab 1. Multiple randomized trials have demonstrated that the addition of rituximab to CHOP significantly improves:

• Event-free survival
• Overall survival
• Complete response rates

Special Considerations for Splenic Involvement

Splenic involvement in stage III DLBCL requires particular attention to:

1. Infection prophylaxis: Patients with functional hyposplenism (due to disease involvement) or who may eventually undergo splenectomy should receive immunization against encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis) 1. Ideally, vaccinations should be given at least 14 days after any splenectomy procedure.

2. Monitoring for complications: Patients with splenic involvement should be monitored for:

   • Cytopenia due to hypersplenism
   • Risk of splenic rupture
   • Potential need for splenectomy in cases of massive splenomegaly or functional compromise

Treatment Duration and Modifications

The standard approach is 6-8 cycles of R-CHOP-21 (21-day cycles). Recent evidence suggests:

• For patients with favorable prognosis (normal LDH, limited stage disease), a shortened course of 4 cycles of R-CHOP may be sufficient 2
• However, for stage III disease with splenic involvement, the full 6-8 cycles is recommended due to higher disease burden

Alternative Regimens

While R-CHOP is the standard of care, alternative regimens may be considered in specific circumstances:

• Bendamustine plus rituximab: May be considered in older patients or those with cardiac comorbidities who cannot tolerate anthracyclines, though this is more commonly used for indolent lymphomas 3

• Dose-adjusted regimens: For elderly patients (60-69 years) with poor prognosis, increased anthracycline and cyclophosphamide doses with interval reduction (ACVBP regimen) has shown improved event-free survival rates compared to standard CHOP 1

Follow-up and Response Assessment

After completion of therapy:

• PET/CT scan to assess treatment response
• Regular clinical follow-up every 3 months for the first 2 years
• Monitor for potential long-term complications of therapy

Common Pitfalls to Avoid

1. Delaying treatment initiation: Stage III DLBCL with splenic involvement requires prompt treatment; watchful waiting is not appropriate for aggressive lymphomas 1

2. Inadequate rituximab dosing: Ensure the full dose of rituximab (375 mg/m²) is administered with each cycle as this significantly improves outcomes 4

3. Overlooking CNS prophylaxis: Consider CNS prophylaxis in high-risk patients (elevated LDH, involvement of specific extranodal sites)

4. Neglecting supportive care: Ensure appropriate antiemetics, growth factor support if needed, and infection prophylaxis

R-CHOP remains the gold standard first-line treatment for stage III DLBCL with splenic involvement based on strong evidence showing improved survival outcomes compared to chemotherapy alone.