Role of Chemotherapy in Laryngeal Diffuse Large B-Cell Lymphoma
Chemotherapy is the cornerstone of treatment for laryngeal diffuse large B-cell lymphoma (DLBCL), with anthracycline-based regimens combined with rituximab (R-CHOP or modified R-COP) representing the standard approach, followed by involved-field radiotherapy in early-stage disease or completion of 6-8 cycles in advanced disease.
Treatment Algorithm Based on Stage and Risk Factors
Early-Stage Disease (Stage I-II)
For patients with stage I-II laryngeal DLBCL without adverse prognostic factors:
- Abbreviated chemotherapy (3-4 cycles) with an anthracycline-containing regimen plus rituximab, followed by involved-field radiotherapy (35-40 Gy) is the preferred approach 1
- Alternatively, a full course of chemotherapy alone (6-8 cycles) can be used 1
- Adverse prognostic factors include: bulky disease, elevated LDH, or ECOG performance status >1 1
For patients with stage I-II disease and at least one adverse prognostic factor:
- Treat according to advanced-stage protocols (see below) 1
Advanced-Stage Disease (Stage III-IV)
Standard first-line therapy consists of:
- R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) administered every 21 days for 6-8 cycles 2, 3, 4
- This regimen achieves 5-year overall survival rates of approximately 76% in young patients with low-risk disease 2
- In elderly patients (60-80 years), R-CHOP results in 2-year overall survival of 70% 2
Specific Considerations for Laryngeal DLBCL
Case reports demonstrate successful treatment approaches:
- Standard R-CHOP protocols (3 cycles followed by involved-field radiotherapy, or 6-8 cycles alone) are applied to laryngeal DLBCL 4
- For elderly patients or those with cardiac dysfunction, modified regimens such as R-COP (omitting doxorubicin) at reduced doses may be necessary 4
- Combination of chemotherapy and radiotherapy is an effective strategy for laryngeal lymphoma 5
Rituximab Dosing and Administration
Initial dosing:
- Rituximab 375 mg/m² IV weekly for 4 doses when used as monotherapy 6, 3
- When combined with chemotherapy (R-CHOP), rituximab is given at 375 mg/m² on day 1 of each 21-day cycle 6, 3
Critical safety monitoring:
- Screen all patients for hepatitis B virus (HBsAg and anti-HBc) before initiating treatment 3
- Monitor for infusion-related reactions, which can be fatal and occur most commonly with the first infusion 3
- Premedicate before each infusion 3
Relapsed or Refractory Disease
For patients under 65 years without complete remission after first-line therapy:
- Non-cross-resistant salvage regimens (ICE, DHAP, MIME, or HDS) with or without rituximab 1
- Patients demonstrating chemosensitivity should proceed to high-dose chemotherapy with autologous stem cell transplant (HDT/autoSCT) 1
- Patients with chemoresistant disease should be enrolled in clinical trials or receive supportive therapy 1
For patients 65 years or older:
- Radioimmunoconjugates or non-cross-resistant chemotherapy 1
Prognostic Factors and Risk Stratification
The International Prognostic Index (IPI) strongly predicts survival:
- Patients with IPI score = 0 (normal LDH, ECOG performance status <2, stage I-II, no bulky disease) have 10-year overall survival of 87-95% 1
- Age ≤65 years is associated with better outcomes 2
- Elevated LDH, poor performance status, and bulky disease indicate higher risk 1, 2
Common Pitfalls and Caveats
Diagnostic challenges:
- Laryngeal lymphoma diagnosis can be difficult, often requiring multiple biopsies to obtain sufficient tissue 4
- Consider lymph node biopsy if laryngeal biopsies are non-diagnostic 4
Treatment modifications:
- Dose-dense chemotherapy is not recommended for very limited-stage disease due to toxicity concerns without clear survival benefit 1
- In elderly patients over 69 years with stage I-II disease, chemotherapy alone may be preferable to combined chemoradiotherapy to avoid radiation toxicity 1
Monitoring requirements: