Compared to B-NHL, Peripheral T cell Lymphomas: 

• Present in more advanced disease 
• Poorer performance status 
• Frequent B symptoms 
• Frequent paraneolastic features such as eosinophilia, HLH etc 
• Higher incidence of autoimmune phenomenon 

PTCL-NOS, includes those cases that do not belong to any of the better defined entities 

Epidemiology: 

• Account for 6% of all NHL 
• Usually seen in adults 
• Common in men 
• Median age- 61 years 
• PTCL-NOS accounts for 50% of all PTCLs. 

Etiology: 

• Risk factors include HTLV1 and EBV infections 

Clinical Features: 

• Bulky lymphadenopathy 
• B symptoms 
• Common extranodal involvement 
• Sometimes- HLH 

Investigations: 

• Lymph node biopsy- Features seen in PTCL- NOS are
  • Diffuse infiltrates of tumor cells with effacement of normal nodal architecture 
  • Very broad cytological spectrum mainly medium to large sized cells 
  • Nuclei are irregular, pleomorphic and may be hyperchromatic with prominent nucleoli 
  • Clear cells and RS like cells often present 
  • High endothelial venules increased 
  • An inflammatory, polymorphous background seen. 
• Immunohistochemistry:
  • T-Cell associated antigens are positive, but there can be loss of one or more antigens (Especially CD7) 
  • Positive- CD45, CD43, CD3
  • 80%  are CD4 + / CD8 –
  • 20% are CD4 – / CD8+ 
• Molecular studies: Clonal rearrangement of the T cell receptor gene 
• Cytogenetics: 
  • Loss of 9p, 5q or 12p.  
  • Gains of 7q, 17q.  
  • Complex cytogenetic abnormalities 
  • t (5:9)- Fusion of IL2 inducible T cell kinase with spleen tyrosine kinase 
• Hemogram- Eosinophilia 
• LDH- Increased 

Prognosis: 

• Generally Poor 
• Overall 5 year survival- 30%  
• T Cell specific International Prognostic Index score: One point given to each of these: 
  • Age >60 years 
  • Raised S. LDH levels 
  • PS- 2-4 
  • Stage III or IV 
  • Extranodal involvement > 1 site 

• Other poor prognostic markers include: 
  • High Ki 67 expression 
  • Extranodal disease 
  • Expression of cytotoxic molecules- TIA-1, Granzyme-B, nm23-H1 protein 
  • TP53 gene abnormality 
  • Chemokine receptor expression- Ex: CCR4 
  • B Symptoms 
  • Bulky disease- >10cm 
  • Raised CRP levels 
  • Platelet count <1,50,000/cmm 
• Loss of 5q, 10q and 12q carry better prognosis 

Pretreatment Work-up for PTCL NOS: 

• History 
  • B-Symptoms 
• Examination 
  • LN: 
  • Spleen: 
  • Full skin exam: 
• WHO P. S. 
• BSA 
• IHC 
• BMA and Bx 
• CT (CAP)/ PET 
• Stage 
• Hemoglobin 
• TLC, DLC 
• Platelet count 
• LFT - Bili- T/D      SGPT:       SGOT: Albumin:    Globulin: 
• Creatinine 
• Electrolytes: Na:       K:       Ca: Mg:        PO4:  
• Uric acid: 
• LDH 
• Beta2 microglobulin 
• HIV:
• HBsAg:
• HCV: 
• HTLV 1 Serology (In high risk population) 
• UPT 
• IPI score 
• ECHO (If anthracyclines planned) LVEF-               %
• Chemotherapy consent after informing about disease, prognosis, cost of therapy, side effects, hygiene, food and contraception
• Fertility preservation
• PICC line insertion and Chest X ray after line insertion
• Tumor board meeting and decision
• Attach supportive care drug sheet
• Inform primary care physician

Treatment Plan for PTCL-NOS:

Indications for CNS prophylaxis

• High IPI score
• High LDH
• Involvement of extranodal site

Other Treatment Options:Targeted therapies

• Sipilizumab:
  • Anti CD2 antibody
  • 0.4-1.2mg/kg- biweekly- for total of 8 doses
  • It triggers T cell apoptosis
• Anti-CD3 antibodies
  • Muromonab: Causes high INF alpha release with severe cytokine syndrome, hence not used
  • Visilizumab: Engages CD3, but does not cause release of TNF alpha
• Zanolimumab:
  • Anti CD4 antibody
  • Has cytotoxic and antiproliferative activity
  • Given biweekly for 6 weeks
  • Dose: early stage: 560mg, Late stage: 980mg
• Alemtuzumab- Anti CD52 antibody
• Brentuximab: Anti CD30 antibody
• Daclizumab- Anti CD 25 antibody
• Anti CD 194 antibody

Recent advances:

Allogeneic hematopoietic stem cell transplantation for NK/T-cell lymphoma: an international collaborative analysis

This retrospective analysis examined the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed/refractory natural killer/T-cell lymphomas (NKTCL). The study included 135 patients who underwent allo-HSCT between 2010 and 2020.  The three-year progression-free survival (PFS) and overall survival (OS) rates were 48.6% and 55.6%, respectively. Shorter time interval between diagnosis and allo-HSCT and transplantation not in complete or partial response were associated with reduced PFS. Pre-transplant treatment with programmed cell death protein 1 (PD-1/PD-L1) inhibitors did not affect graft-versus-host disease or survival. 

https://doi.org/10.1038/s41375-023-01924-x

CHOEP plus lenalidomide as initial therapy for patients with stage II–IV peripheral T-cell lymphoma

In this phase II study, a novel induction strategy for nodal-based peripheral T-cell lymphoma (PTCL) was evaluated using lenalidomide in combination with CHOEP chemotherapy. Patients received standard doses of CHOEP along with 10 mg of lenalidomide on days 1–10 of a 21-day cycle for six cycles. Among 39 evaluated patients, the objective response rate after six cycles was 69%, with complete response in 49% and partial response in 21%. However, hematologic toxicity, including febrile neutropenia, was a significant issue, leading to treatment discontinuation in some cases. Despite these challenges, the estimated 2-year progression-free and overall survival rates were 55% and 78%, respectively. 

https://doi.org/10.1111/bjh.18885