What is the recommended treatment for stage I diffuse large B‑cell lymphoma?

Treatment for Stage I Diffuse Large B-Cell Lymphoma

For stage I DLBCL, administer 3 cycles of R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days) followed by involved-field radiotherapy to the affected site. 1

Treatment Regimen Details

Standard Abbreviated Chemotherapy Plus Radiotherapy

• Young patients with stage I disease (aaIPI 0-1) should receive 3 cycles of R-CHOP-21 followed by involved-field radiation therapy. 1
• This abbreviated approach is specifically validated for early-stage (stage I-II) disease in good-risk patients. 1
• The R-CHOP-21 regimen 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 (maximum 2 mg) IV on day 1
  • Prednisone 40-100 mg/m² orally on days 1-5
  • Cycles repeated every 21 days 2, 3

Alternative Full-Course Chemotherapy

• If radiotherapy is contraindicated or declined, administer 6 cycles of R-CHOP-21 without radiation. 1, 2
• Six cycles of R-CHOP-21 alone represents the standard approach when radiotherapy cannot be delivered. 1, 2

Age-Specific Modifications

Patients Aged 60-80 Years

• If the patient is 60-80 years old with stage I disease, use 6-8 cycles of R-CHOP-21 (typically 8 cycles) rather than the abbreviated 3-cycle approach. 1, 2
• Consolidation radiotherapy after full-course chemotherapy provides no proven benefit in this age group and should not be routinely added. 1, 2

Patients Over Age 80

• Perform a comprehensive geriatric assessment before treatment to evaluate for frailty, cardiac function, renal function, and functional status. 2, 4
• Fit patients over 80 may receive standard R-CHOP-21 (6 cycles for stage I). 2, 4
• For frail patients over 80, consider R-miniCHOP (attenuated doses) which can still achieve complete remission and prolonged survival. 2, 4
• In patients with cardiac dysfunction (ejection fraction <50%), substitute doxorubicin with etoposide or liposomal doxorubicin, or omit doxorubicin after initial cycles. 4

Critical Pre-Treatment Measures

Tumor Lysis Syndrome Prevention

• Screen all patients for elevated LDH, high tumor burden, and renal function before starting treatment. 1
• For patients with bulky stage I disease or high tumor burden, administer prednisone 100 mg orally daily for 5-7 days as "pre-phase" treatment before starting R-CHOP. 5, 2, 4
• Ensure adequate hydration and provide allopurinol 300 mg daily or rasburicase in highest-risk patients. 2, 4

Infectious Disease Screening

• All patients must be screened for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before rituximab administration. 2
• HBsAg-positive patients require prophylactic entecavir throughout treatment and for 12 months after rituximab completion. 2
• Screen for HIV and hepatitis C as well. 1, 2

Cardiac Assessment

• Measure left ventricular ejection fraction (LVEF) before starting doxorubicin-containing chemotherapy. 1
• LVEF <50% requires doxorubicin modification or substitution. 4

Supportive Care Requirements

Growth Factor Support

• Administer primary prophylactic G-CSF (granulocyte colony-stimulating factor) to all patients over age 65 and to younger patients receiving curative-intent therapy who develop febrile neutropenia. 1, 2, 4
• G-CSF should be given starting 24-72 hours after chemotherapy and continued until neutrophil recovery. 2

Dose Management

• Avoid routine dose reductions for hematologic toxicity; maintain full doses to preserve treatment efficacy. 1, 5, 2, 4
• Dose reductions should only be made for life-threatening toxicity, not for uncomplicated neutropenia. 2, 4

CNS Prophylaxis Considerations for Stage I Disease

• CNS prophylaxis is generally NOT required for stage I disease unless specific high-risk features are present. 2
• Consider CNS prophylaxis if stage I disease involves:
  • Testicular involvement (mandatory CNS prophylaxis plus contralateral testis irradiation) 1, 2, 4
  • Paranasal sinus involvement 2
  • Elevated LDH with additional high-risk features 2
• When indicated, use intravenous high-dose methotrexate (3-3.5 g/m²) rather than intrathecal methotrexate alone. 2, 4

Response Assessment

Interim Evaluation

• Perform CT or PET-CT imaging after 3 cycles (before radiotherapy) to assess response. 1, 5
• If PET-CT is used, apply the Deauville 5-point scale for interpretation. 2, 4

End-of-Treatment Assessment

• Obtain PET-CT 6-8 weeks after completing all therapy (chemotherapy plus radiotherapy) to define complete remission. 1, 5, 2, 4
• Deauville score 1-3 indicates complete metabolic response. 2, 4
• If PET remains positive (Deauville 4-5) and will change management, obtain histologic confirmation via biopsy before declaring treatment failure. 1, 2, 4
• Bone marrow biopsy is NOT needed at end of treatment for stage I disease unless marrow was involved at diagnosis. 1, 2

Common Pitfalls to Avoid

• Do not use R-CHOP-14 (every 14 days) instead of R-CHOP-21; dose-dense scheduling provides no survival benefit and increases toxicity. 2, 3
• Do not omit radiotherapy in young patients with stage I disease receiving only 3 cycles of chemotherapy; the abbreviated regimen requires radiation consolidation. 1
• Do not add consolidation radiotherapy to 6-8 cycles of R-CHOP in patients over 60; this provides no benefit in the rituximab era. 1, 2
• Do not skip geriatric assessment in patients over 80 before committing to full-dose therapy. 2, 4
• Do not reduce chemotherapy doses after pre-phase corticosteroid treatment due to transient cytopenias; this compromises cure rates. 2, 4
• Do not forget CNS prophylaxis and contralateral testis irradiation in stage I testicular DLBCL. 1, 2, 4