What is the recommended treatment for a patient with high-grade T-cell lymphoma and a Ki-67 (proliferation index) of 100%?

Treatment for High-Grade T-Cell Lymphoma with Ki-67 of 100%

For high-grade T-cell lymphoma with a Ki-67 of 100%, intensive chemotherapy followed by early allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the recommended treatment approach.

Initial Treatment Strategy

Aggressive T-Cell Lymphoma Treatment Approach

For patients with high-grade T-cell lymphoma and a Ki-67 of 100%, the treatment should follow the recommendations for aggressive Adult T-cell Leukemia-Lymphoma (ATL) subtypes:

1. First-line therapy:

   • Intensive chemotherapy regimens 1:
     • Outside Japan: CHOP (cyclophosphamide, vincristine, doxorubicin, prednisolone), CHOEP (CHOP plus etoposide), or DA-EPOCH (dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin)
     • In Japan: VCAP-AMP-VECP (modified LSG15)

2. Consolidation therapy:

   • Early up-front allogeneic hematopoietic stem cell transplantation (allo-HSCT) for all eligible patients 1

Rationale for Intensive Approach

The extremely high Ki-67 proliferation index (100%) indicates a highly aggressive disease with rapid cell turnover. A Ki-67 index >30% is considered high-risk in lymphomas 1, and 100% represents the most aggressive end of the spectrum. This necessitates immediate intensive therapy.

CNS Prophylaxis

Prophylactic CNS therapy should be considered for all patients with aggressive T-cell lymphoma 1:

• Diagnostic lumbar puncture/intrathecal chemotherapy should be performed at the end of the first chemotherapy cycle
• Consider incorporating high-dose methotrexate into combination chemotherapy regimens for patients at high risk of CNS involvement

Treatment Considerations for Specific Patient Groups

For Transplant-Eligible Patients

• Complete intensive chemotherapy induction
• Proceed to allo-HSCT as consolidation while disease is controlled
• Early referral to a transplantation center at diagnosis is strongly recommended 1

For Elderly or Transplant-Ineligible Patients

• Reduced dose of chemotherapy
• Consider maintenance strategies after first-line therapy:
  • Oral chemotherapy (etoposide, sobuzoxane)
  • Where available, zidovudine/interferon-alpha (AZT/IFN) with or without arsenic trioxide (ATO) 1

Monitoring and Response Assessment

• Regular assessment of treatment response with imaging studies
• Careful monitoring for treatment-related toxicities
• Early identification of disease progression to allow for timely change in therapeutic approach

Management of Relapsed/Refractory Disease

For relapsed or refractory disease 1:

• Single agents or alternative combination chemotherapy regimens containing platinum, etoposide, and/or high-dose cytarabine
• Consider clinical trials when available
• Localized radiotherapy for palliation

Important Caveats

1. Prognostic significance of Ki-67: A very high Ki-67 index (100%) indicates extremely aggressive disease requiring immediate intensive therapy. In some lymphoma subtypes, very high Ki-67 (>80%) has been associated with better response to intensive chemotherapy, though with high risk of early relapse 2.

2. Treatment toxicity: Intensive chemotherapy regimens carry significant toxicity risks. Fatal toxic reactions occur in 1-6% of patients receiving intensive lymphoma regimens 3.

3. Importance of early transplantation: With progressive disease, clinical outcomes after allo-HSCT are poor. It is crucial to conduct up-front allo-HSCT while the lymphoma is controlled to maximize cure rates 1.

4. CNS risk: High-grade T-cell lymphomas have significant risk of CNS involvement, making prophylactic CNS therapy essential 1.