Treatment for T-Cell Lymphoma
Treatment for T-cell lymphoma depends critically on the specific histologic subtype, stage, and CD30 expression status, with combination chemotherapy followed by autologous stem cell transplantation representing the standard approach for most peripheral T-cell lymphomas, while cutaneous variants require stage-adapted skin-directed therapies for early disease.
Treatment by Histologic Subtype
Peripheral T-Cell Lymphomas (PTCL-NOS, AITL, ALCL)
First-Line Treatment for Systemic Disease
For previously untreated systemic ALCL or other CD30-expressing PTCL (≥1% CD30 expression), brentuximab vedotin plus CHP (cyclophosphamide, doxorubicin, prednisone) is the preferred first-line regimen, administered at 1.8 mg/kg (maximum 180 mg) every 3 weeks for 6-8 cycles. 1, 2 This represents a Category 1 recommendation for ALCL and Category 2A for other CD30-positive histologies. 1
For ALCL ALK-positive with low-risk profile (IPI ≤2), use 6 cycles of multiagent chemotherapy with or without involved-site radiotherapy for stage III-IV disease, or 3-4 cycles with radiotherapy for stage I-II disease. 1
For ALCL ALK-positive with high-risk profile (IPI >2), consolidation with autologous stem cell transplantation should be considered after achieving remission. 1
For PTCL-NOS, AITL, and ALCL ALK-negative without DUSP22 rearrangement, clinical trial enrollment is strongly preferred over standard chemotherapy. 1
Alternative chemotherapy regimens include CHOEP (CHOP plus etoposide), dose-adjusted EPOCH, or hyper-CVAD when brentuximab vedotin is unavailable. 1
Consolidation Strategy
For patients achieving complete or partial remission after induction chemotherapy, high-dose chemotherapy followed by autologous stem cell transplantation is recommended as consolidation therapy. 1 This approach has demonstrated improved progression-free and overall survival in multiple studies. 1
Enteropathy-Associated T-Cell Lymphoma (EATL)
CHOP followed by IVE (ifosfamide, etoposide, epirubicin) alternating with intermediate-dose methotrexate is recommended as first-line therapy, resulting in 5-year progression-free survival of 52% compared to 22% with conventional anthracycline-based regimens alone. 1, 3
Patients typically present with severe malabsorption, weight loss, and nutritional deficiencies requiring comprehensive nutritional support throughout treatment. 3
EATL carries an extremely poor prognosis with median overall survival of 10 months, necessitating aggressive multimodal therapy when feasible. 3
Extranodal NK/T-Cell Lymphoma (ENKTCL)
Stage I-II Disease
Concurrent chemoradiotherapy or sequential L-asparaginase-containing chemotherapy followed by radiation (>50 Gy alone or ~40 Gy with cisplatin radiosensitization) is the preferred treatment for localized nasal disease. 1
Central nervous system prophylaxis is not recommended even when nasal/paranasal areas are involved. 1
Stage III-IV Disease
L-asparaginase-containing chemotherapy regimens (SMILE or AspaMetDex) should be used as front-line treatment. 1
If complete remission is achieved, high-dose chemotherapy with autologous stem cell transplantation is recommended, preferred over allogeneic transplantation due to lower treatment-related mortality. 1
For elderly or frail patients, single-agent L-asparaginase or dose-modified regimens are appropriate. 1
Adult T-Cell Leukemia-Lymphoma (ATL)
Acute and Lymphoma-Type ATL
For acute ATL with nonbulky disease, either zidovudine/interferon-alpha or intensive chemotherapy may be considered where zidovudine/interferon-alpha is available. 1
For bulky acute subtypes or lymphoma-type ATL, intensive chemotherapy is required. 1
Early upfront allogeneic stem cell transplantation should be considered for all eligible patients with aggressive ATL. 1
Chronic and Smoldering ATL
Favorable chronic ATL may be managed with active monitoring or zidovudine/interferon-alpha with or without arsenic trioxide. 1
Unfavorable chronic ATL should receive zidovudine/interferon-alpha with or without arsenic trioxide continued indefinitely unless progressive disease occurs. 1
Cutaneous T-Cell Lymphomas (Mycosis Fungoides/Sézary Syndrome)
Early-Stage Disease (IA-IIA)
Skin-directed therapies including topical steroids, ultraviolet B phototherapy, PUVA (psoralen plus UVA), or localized radiotherapy are the preferred initial treatments for early-stage mycosis fungoides. 1
Stage I disease with limited skin involvement may be treated with shortened chemotherapy (3 courses) followed by radiotherapy. 1
Advanced-Stage Disease (IIB-IV)
Systemic therapies including extracorporeal photopheresis, interferon-alpha, low-dose methotrexate, or bexarotene are appropriate for advanced cutaneous disease. 1
For CD30-positive cutaneous ALCL with extensive disease or systemic progression, brentuximab vedotin at 1.8 mg/kg (maximum 180 mg) every 3 weeks for up to 16 cycles is indicated. 1, 2
Reduced-intensity allogeneic stem cell transplantation should be considered for selected patients with advanced refractory disease. 1
Relapsed/Refractory Disease
CD30-Positive Subtypes
Brentuximab vedotin monotherapy at 1.8 mg/kg (maximum 180 mg) every 3 weeks is the preferred treatment for relapsed systemic ALCL, achieving an 86% overall response rate. 1, 2 Responses have been observed even in patients with low CD30 expression. 1
Other Relapsed PTCL
Salvage chemotherapy regimens include DHAP (dexamethasone, high-dose cytarabine, cisplatin), ICE (ifosfamide, etoposide, carboplatin), or IVAC (ifosfamide, cytarabine, etoposide). 1
For early relapse (<12 months) after anthracycline-based treatment of ENKTCL, L-asparaginase-containing regimens are recommended. 1
Pralatrexate and romidepsin are FDA-approved options for relapsed/refractory disease (not EMA-approved). 1
Either autologous or allogeneic stem cell transplantation should be considered in transplant-eligible patients achieving chemosensitive disease. 1
Critical Treatment Considerations
Hepatosplenic T-Cell Lymphoma
This subtype has one of the worst prognoses among PTCLs with 5-year failure-free survival and overall survival rates less than 10%. 1
All cases require chemotherapy at diagnosis despite typically brief responses to anthracycline-based therapy. 1
Both autologous and allogeneic stem cell transplantation should be offered to all eligible patients. 1
Common Pitfalls
Avoid delaying stem cell transplantation in eligible patients with aggressive subtypes, as consolidation in first remission significantly improves outcomes. 1
Do not use aggressive chemotherapy for early-stage cutaneous T-cell lymphomas, as skin-directed therapies provide equivalent survival with better quality of life. 1
Ensure adequate L-asparaginase dosing in ENKTCL and do not substitute with less effective agents. 1
Monitor for progressive multifocal leukoencephalopathy (PML) in patients receiving brentuximab vedotin, as JC virus infection can result in PML and death. 2