T-cell Lymphomas

Name: T-cell Lymphomas: Mini Review for Clinicians, Algorithms & Cases
Creator: Dr. Haritha Chiramana
License: https://creativecommons.org/licenses/by-nc-nd/4.0/

Haematological cancers, part 4 · PTCL-NOS, T follicular helper (angioimmunoblastic), systemic anaplastic large cell (ALK+/ALK−), extranodal NK/T, ATLL and T-PLL · CD30 and BV-CHP · Consolidation · Relapse · Key points for clinicians · Last updated 17 October 2026

For health professionals. This section uses clinical terms and is general education for doctors, nurses and students, not advice for an individual patient. Patients and families: please read our patient guides instead, Cancer Myth Busters · Understanding your cancer report · Living through cancer treatment, or speak with your own doctor.

Who this page is for, and where to start

Printable PDFs for this moduleMini reviews, slides, algorithms, quick references and the MCQ booklet are on the Printable Teaching Resources page. No PDF downloads are kept on this page.

Printable Teaching Resources →

For your patientsPlain-language Telugu–English answers for patients and families: the Lymphoma Myth Busters (27 myths), symptoms and warning signs and the Telugu handouts.

Open the lymphoma myths →

SurgeonsScreening and workup (03), local therapy with surgery types (05), algorithms (07), cases (11)

Physicians & oncologistsBiomarkers (04), systemic therapy (06), algorithms (07), survivorship (08), cases (11)

Postgraduate residentsOncology and other specialities: case vignettes (11), landmark trials (09) and 0 cited trials (12) for exams and journal clubs

Medical studentsAt a glance (01), presentation and common traps (02), the figures, and follow-up (08)

Prepared and reviewed by Dr. Haritha Chiramana, MD, DM, Senior Medical Oncologist & Hemato-Oncologist, C.R. Reddy Cancer Center, Nellore, Andhra Pradesh, India. She teaches oncology to postgraduates and medical students; colleges and departments may write to info@drharitha.co.in for teaching sessions. Printable Teaching Resources and how to cite → Phone 0861 232 5344 · WhatsApp +91 79896 42272.

01 At a glance

Peripheral T-cell lymphomas (PTCL) are rare and varied: about 10% of non-Hodgkin lymphomas in the West and 15–20% in Asia. The main systemic types are PTCL, NOS; nodal T follicular helper (TFH) lymphoma, angioimmunoblastic type (AITL); systemic anaplastic large cell lymphoma (ALCL, ALK-positive or ALK-negative); extranodal NK/T-cell lymphoma, nasal type; ATLL; and T-PLL.
Diagnosis needs an excision biopsy and an expert haematopathologist: PTCL-NOS is a diagnosis of exclusion; CD30, ALK, TFH markers, EBER and HTLV-1 testing name the entity.
CD30 chooses first-line treatment: CD30-positive (at least 1% of cells, including all ALCL) → brentuximab vedotin with CHP (ECHELON-2^[1]); CD30-negative → CHOEP if fit and about 65 or younger, CHOP otherwise.
Outcome depends on the entity: ALK-positive ALCL does well (3-year OS about 90%); PTCL-NOS, AITL and ALK-negative ALCL relapse often; relapsed PTCL without transplant has a median survival of about 6 months.
Response-guided care: PET after three cycles and at the end; consolidation (RT for limited residual disease; autologous transplant for selected fit patients) is decided at the end of induction.
Relapse: biopsy; BV for BV-naïve ALCL, crizotinib for ALK-positive ALCL, single agents (belinostat, pralatrexate, romidepsin) or combination salvage for PTCL, and transplant as the only route to long-term control.
India: ALCL is relatively frequent (4.3% of NHL at Tata Memorial), and PTCL and nasal NK/T lymphoma are more common than in the West: a necrotic nasal mass needs a deep biopsy.

Figure 1. T-cell lymphomas at a glance (UpToDate PTCL-NOS, AITL, sALCL, ENKTL, ATLL and T-PLL reviews).

02 Clinical presentation, common traps & causes

Figure 2. Entities and clues (UpToDate diagnosis reviews); Indian data from Naresh 2000 and a 2020 Bihar series.

Who gets it, and why

PTCL-NOS: median age about 60; the commonest PTCL outside Asia (about a third of cases); in Asia, NK/T-cell lymphoma is commoner.
AITL: older adults with an acute systemic illness: generalised nodes (76–95%), splenomegaly (70%), B symptoms (70–85%), itchy rash (20–60%), arthritis, effusions; 90% stage III–IV; polyclonal hypergammaglobulinaemia, autoimmune haemolysis.
ALCL: about 2% of adult NHL; ALK-positive disease in children and young adults, ALK-negative in older adults; male predominance; fast-growing nodes with skin, bone, liver, lung or CNS disease.
NK/T-cell lymphoma: EBV in every case; commonest in East Asia and Central and South America; nose, sinus and palate (stage I 43%, II 22% in one series).
ATLL: HTLV-1 carriers, after decades of latency (lifetime risk 4–5% in endemic areas: southwest Japan, the Caribbean, west Africa, Peru, northeast Iran). T-PLL: older adults; much more common with ataxia-telangiectasia.
India: in 2773 lymphomas at Tata Memorial, ALCL was 4.3% and other nodal PTCL 2.9% of NHL; ALCL and T-lymphoblastic lymphoma were relatively commoner than in the West (Naresh 2000^[2]); a Bihar series found PTCL and nasal NK/T lymphoma less common than in some Asian countries but commoner than in the West (Bihar 2020^[3]).

Common traps

Fever, nodes and rash treated as infection or drug allergy for weeks. AITL looks like a systemic infection or autoimmune disease: biopsy a node early.
"Reactive" or "atypical lymphoid infiltrate" on a core. T-cell lymphomas need architecture and a large panel: excise a whole node.
A necrotic nasal ulcer called fungal sinusitis or granulomatosis. Superficial biopsies show only necrosis; ask for deep biopsies and EBER.
CD30 not reported. It decides first-line treatment: ask for it on every PTCL.
Hypercalcaemia and "Sézary-like" cells in a patient from an HTLV-1 area. Test HTLV-1 before calling it mycosis fungoides or PTCL.
Missing HLH. Fever, cytopenias, very high ferritin: hemophagocytic lymphohistiocytosis can complicate PTCL and needs urgent treatment.

03 Diagnosis, workup & staging essentials

Making the diagnosis

Excision or incision biopsy of a node (or deep biopsies of the involved organ); fresh tissue for flow cytometry where possible; expert haematopathology review.
PTCL-NOS: one or more pan-T antigens (CD2, CD3, CD5, CD7), often with loss of CD5 or CD7; clonal TCR; no specific cytogenetics; diagnosis only after excluding other types.
TFH lymphoma (AITL): effaced node, arborising high endothelial venules, expanded CD21-positive dendritic meshworks; CD4 plus at least two TFH markers (PD-1, ICOS, CXCL13, BCL6, CD10); EBV-positive B blasts are common.
ALCL: sheets of large "hallmark" cells with strong membrane and Golgi CD30; ALK by IHC or FISH (NPM::ALK) separates ALK-positive from ALK-negative; DUSP22 rearrangement in up to a third of ALK-negative cases. Exclude primary cutaneous and breast implant-associated ALCL.
NK/T-cell lymphoma: necrosis, angioinvasion, CD56, cytoplasmic CD3, cytotoxic granules, and EBER in virtually all.
ATLL: flower cells, CD4+CD25+CD7−, and HTLV-1 serology (confirmatory blot or PCR); at least 5% abnormal T cells in blood plus HTLV-1 can establish leukaemic forms (Shimoyama 1991^[4], Cook 2019^[5]).
T-PLL: over 5000/µL clonal T cells with TCL1 or MTCP1 abnormality (inv(14), t(14;14), t(X;14)); HTLV-1 negative (Staber 2019^[6]).

Figure 3. T-cell lymphoma key (UpToDate PTCL-NOS, AITL, sALCL, ENKTL, ATLL and T-PLL diagnosis reviews; simplified).

Before treatment

Area	What to do	Why
History and examination	B symptoms, rash, nasal and palatal examination, skin, liver, spleen, performance status, comorbidities, country of origin (HTLV-1)	Entity, stage, fitness
Blood tests	CBC and smear, chemistry, calcium, LDH, uric acid, immunoglobulins, DAT, ferritin if febrile and cytopenic	IPI/PIT; hypercalcaemia (ATLL); haemolysis (AITL); HLH
Viruses	HBV, HCV, HIV; HTLV-1 where relevant; EBV (EBER on tissue)	Prophylaxis; ATLL; NK/T diagnosis
Imaging	PET-CT; MRI of nose and sinuses for NK/T lymphoma	Stage; baseline for interim and end PET
Marrow	Biopsy when it changes management (cytopenias, PIT, T-PLL)	PIT score; stage
Heart and fertility	Echocardiogram before anthracyclines; sperm banking, fertility counselling	CHOP-based treatment; transplant plans
Transplant assessment	Fitness and donor search planned early for fit patients	Relapses come early

Figure 4. Prognosis (Gallamini 2004, PIT; Vose 2008, International T-cell Project; UpToDate PTCL-NOS and sALCL reviews).

04 Biology and biomarkers that change treatment

Marker or feature	What it tells you	What it changes
CD30 (≥1% of tumour cells)	All ALCL; a share of PTCL-NOS and AITL	BV-CHP first line; BV at relapse
ALK (IHC or FISH)	ALK-positive ALCL: young, curable (3-year OS about 90% vs 62%)	No transplant in first CR; crizotinib at relapse
DUSP22 rearrangement (ALK− ALCL)	Up to a third; prognostic meaning debated	Not used for treatment choice yet
TFH markers (PD-1, ICOS, CXCL13, BCL6, CD10)	Nodal TFH lymphoma (AITL and related)	Same first-line approach; azacitidine studied at relapse (ORACLE^[7])
EBV (EBER)	NK/T-cell lymphoma (all); EBV+ B blasts in AITL	NK/T diagnosis; watch for EBV-driven B-cell proliferations
HTLV-1	ATLL in every case	Different disease, different treatment; family screening
TCL1 / MTCP1, inv(14)	T-PLL	Distinguishes it from ATLL and Sézary

Figure 5. First line (Horwitz 2019 and 2022, ECHELON-2; Ellin 2014, Swedish registry; UpToDate initial PTCL and sALCL reviews).

05 Local therapy: radiotherapy & surgery

Radiotherapy

Stage I PTCL with a favourable prognosis in complete or partial response after chemotherapy: adjuvant RT.
Limited-stage ALCL in complete response: observation or RT; limited residual disease: RT to convert the response, then transplant in eligible ALK-negative patients.
Advanced disease with a single residual site: RT, followed by autologous transplant in fit patients with PTCL-NOS, AITL or ALK-negative ALCL; RT alone for ALK-positive ALCL and for patients who cannot have a transplant.
NK/T-cell lymphoma: RT is part of combined-modality treatment for localised disease (about 50 Gy ISRT in sandwich protocols; inadequate RT dose is a cause of local failure); RT alone for less-fit patients with localised disease.

Surgery

Diagnosis: excision biopsy is the main role; deep biopsies for nasal disease.
Emergencies: perforation or bleeding from intestinal T-cell lymphoma; airway compromise from nasal or pharyngeal disease.

06 Systemic therapy: indications & options

PTCL-NOS, TFH lymphoma (AITL) and EATL: first line

CD30-positive (≥1%): BV-CHP for six cycles. In ECHELON-2 (452 patients, mostly ALCL), BV-CHP improved PFS and OS over CHOP; in the 72 patients with other subtypes the gain was not significant (AITL 5-year OS 68% vs 63%) (ECHELON-2^[1], five-year update^[8]).
CD30-negative, fit, about 65 or younger: CHOEP; in the Swedish registry CHOEP gave better PFS than CHOP under 60 (HR 0.49) (Ellin 2014^[9]; Schmitz 2010^[10]). Older or less fit: CHOP.
Interim PET after three cycles: CR or PR → complete six cycles; stable or progressive → treat as refractory.
After induction (end-of-treatment PET): stage I favourable → RT; advanced, fit, in CR → observation or autologous transplant (NLG-T-01^[11]); single residual site → RT then autologous transplant; extensive residual → refractory pathway. Not transplant-eligible → RT for CR or limited residual disease.

Figure 6. Consolidation (d'Amore 2012, NLG-T-01; meta-analyses as quoted in the UpToDate initial PTCL and sALCL reviews).

Systemic anaplastic large cell lymphoma: first line

BV-CHP for every systemic ALCL (ALK-positive or negative) rather than CHOP: in the 316 ALCL patients of ECHELON-2, 5-year PFS 61% vs 48% (HR 0.55) with a trend to better survival.
Interim PET after 3–4 cycles, then complete six cycles if responding.
ALK-positive, advanced, CR: observe (no transplant); limited PR → RT. ALK-negative, advanced, CR: observation or autologous transplant; limited PR → RT then autologous transplant. Extensive PR → relapsed/refractory pathway.
Frail patients: single-agent BV. Children: clinical trials or paediatric protocols.

Relapsed or refractory PTCL and ALCL

Figure 7. Relapsed disease (Pro 2012 and 2017, BV; Mossé 2013 and paediatric crizotinib series; O'Connor 2015, BELIEF; Falchi 2021; Dupuis 2024, ORACLE; UpToDate reviews).

Biopsy to confirm relapse and check for a change in histology; trials whenever possible.
sALCL, relapse after 6 months or BV-naïve refractory: BV alone (73% response, 46% complete in BV-naïve patients) (Pro 2012^[12], Pro 2017^[13]). Early or BV-refractory: ALK-positive → crizotinib (88% response in patients aged 21 or under; Mossé 2013^[14]); ALK-negative → belinostat, romidepsin or pralatrexate.
After response: ALK-positive, no prior transplant → autologous transplant; prior autologous transplant → observe. ALK-negative → autologous, allogeneic or observation.
PTCL-NOS and AITL, transplant-eligible: combination salvage as a bridge; CR without prior autologous transplant → autologous; prior autologous transplant, PR, or several lines needed → allogeneic (reduced intensity if older).
Primary refractory, relapse within 6 months, or multiple relapses: a newer agent rather than combination chemotherapy. Not transplant-eligible: sequential single agents (belinostat 26% response; BELIEF^[15]; PROPEL^[16]). Oral azacitidine for TFH lymphoma did not meet its endpoint (median PFS 5.6 vs 2.8 months; ORACLE^[7]); azacitidine-romidepsin was active in a phase 2 study (Falchi 2021^[17]).

Extranodal NK/T-cell lymphoma, nasal type

Figure 8. ENKTL (UpToDate ENKTL diagnosis and treatment reviews; Kim 2016, PINK; Yamaguchi 2009 and 2011; Kim 2009; Kwong 2017).

Evaluate at an experienced centre: examination, fibre-optic endoscopy, PET-CT, marrow, plasma EBV DNA. Localised = stage IE or contiguous IIE (cervical nodes); advanced = non-contiguous II, III–IV and all non-nasal disease. Prognosis: PINK and PINK-E (with EBV load) (Kim 2016^[18]).
Localised, fit: combined-modality treatment with asparaginase- or platinum-based chemotherapy and RT rather than anthracyclines, chemotherapy alone or RT alone. Options: concurrent chemoradiotherapy with reduced-dose DeVIC (JCOG0211^[19]) or RT with cisplatin followed by VIDL/VIPD (Kim 2009^[20]); or sequential/sandwich treatment with modified SMILE or P-GEMOX around ISRT of about 50 Gy. Systemic failure still occurs in 25–50%.
After treatment: CR → observation; less than CR → transplant (the only reliable cure in this setting), with bridging if needed.
Advanced: asparaginase-based induction (modified SMILE, DDGP or P-GEMOX; SMILE^[21]), then transplant for CR or PR.
Less fit: localised → RT alone or lower-intensity CMT (GDP or MGAD); advanced → GDP, with RT for bulky symptomatic disease.
Relapsed or refractory: salvage before transplant; a PD-1 antibody before planned autologous transplant (pembrolizumab highly active: Kwong 2017^[22]), asparaginase or other chemotherapy otherwise; transplant is the only proven cure.

ATLL and T-PLL

Figure 9. ATLL and T-PLL (UpToDate ATLL and T-PLL diagnosis and treatment reviews; Staber 2019; Tsukasaki 2007; Dearden 2001).

ATLL, acute, lymphomatous or unfavourable chronic: VCAP-AMP-VECP (better than biweekly CHOP; JCOG9801^[23]), with mogamulizumab where available (CR 52% vs 33%, median PFS 8.5 vs 6.3 months; Ishida 2015^[24]); avoid mogamulizumab before allogeneic transplant (graft-versus-host risk). Older or comorbid: CHOP or CHOP-like. Always intrathecal prophylaxis. Trials encouraged.
After remission: allogeneic transplant for patients with a donor (graft-versus-leukaemia effect). Zidovudine plus interferon alfa has been used, with median survival of 6–18 months in reported series (Bazarbachi 2010^[25]).
Typical chronic and smouldering ATLL: no immediate treatment; median survival of smouldering disease untreated is about 3 years. Treat infections and hypercalcaemia; prophylaxis against opportunistic infections.
T-PLL, inactive: close observation with monthly blood counts. Active (B symptoms, enlarging nodes, spleen or liver, marrow failure, extramedullary disease, rapidly rising count): IV alemtuzumab alone; add pentostatin if progression, stable disease at 4–6 weeks or less than CR at 10–12 weeks (Dearden 2001^[26]).
T-PLL consolidation: transplant in CR (allogeneic for younger fit patients; autologous if not a candidate). Relapse: trials. Median survival with modern treatment is 1–3 years.

India now (October 2026)

Indian frequencies (Tata Memorial 2000; Bihar 2020) are web-verified; HTLV-1 is not endemic in India, but ATLL is seen in people from endemic regions.
Availability and cost of brentuximab vedotin, crizotinib, belinostat, pralatrexate, romidepsin, pegaspargase, PD-1 antibodies, mogamulizumab and alemtuzumab in India, and access to transplant, to be confirmed by the treating team.

Quick reference (also as a printable PDF on the Printable Teaching Resources page)

Table A. Diagnosis and staging tests and what they change

Test	When	What it changes	Pitfalls
Excision biopsy (deep biopsies for nasal disease)	Every suspected case	Entity	Cores and superficial biopsies miss architecture or show only necrosis
IHC: CD3, CD4, CD8, CD30, ALK, PD-1/ICOS/CXCL13, CD56, granzyme; EBER	Every biopsy	ALCL ALK±, TFH lymphoma, NK/T, PTCL-NOS	CD30 must be quantified (≥1% counts)
HTLV-1 serology (blot or PCR)	Abnormal T cells in blood, hypercalcaemia, origin in endemic areas	ATLL	Healthy carriers can have flower cells
Flow cytometry, TCL1, karyotype/FISH	High T-cell counts	T-PLL vs ATLL vs Sézary	TCL1-negative T-PLL exists (minor criteria)
PET-CT; MRI nose and sinuses	Staging; interim (after 3 cycles) and end of treatment	Stage; response-guided plan	Inflammation and infection take up FDG
LDH, calcium, ferritin, DAT, immunoglobulins	Baseline	IPI/PIT; ATLL; HLH; haemolysis in AITL	Ferritin very high with cytopenias: think HLH
HBV, HCV, HIV	Before treatment	Prophylaxis	—

Table B. Treatment by setting

Setting	Standard choice	Key evidence	Notes
CD30-positive PTCL (incl. all systemic ALCL)	BV-CHP × 6	ECHELON-2^[1]	Benefit clearest in ALCL
CD30-negative PTCL, fit ≤65	CHOEP × 6	Ellin 2014^[9]	Interim PET after 3 cycles
CD30-negative PTCL, older or less fit	CHOP × 6	UpToDate initial PTCL review	RT for residual disease
PTCL/ALK− ALCL, advanced, fit, CR	Observation or autologous HCT	NLG-T-01^[11]	No randomised proof of survival gain
ALK+ ALCL, CR	Observation	UpToDate sALCL review	No transplant in first CR
Stage I favourable PTCL, CR/PR	Adjuvant RT	UpToDate initial PTCL review	—
Relapsed sALCL, late or BV-naïve	BV	Pro 2012^[12]	Then HCT if fit
Relapsed ALK+ ALCL, early or BV-refractory	Crizotinib	Mossé 2013^[14]	Young patients best studied
Relapsed PTCL, transplant-eligible	Combination salvage → auto or allo HCT	UpToDate relapsed PTCL review	Newer agent if early or multiple relapse
Relapsed PTCL, not eligible	Sequential single agents	BELIEF^[15], PROPEL^[16]	Trials; palliative care
NK/T, localised	Asparaginase- or platinum-based chemotherapy + RT (concurrent or sandwich)	JCOG0211^[19], Kim 2009^[20]	No anthracyclines; CR → observe
NK/T, advanced	m-SMILE, DDGP or P-GEMOX → HCT	SMILE^[21]	Relapse: PD-1 antibody before auto-HCT
ATLL, aggressive types	VCAP-AMP-VECP ± mogamulizumab (or CHOP if unfit), IT prophylaxis → allo-HCT	JCOG9801^[23], Ishida 2015^[24]	No mogamulizumab before allo-HCT; chronic/smouldering: watch
T-PLL, active	IV alemtuzumab (+ pentostatin if suboptimal) → HCT in CR	Dearden 2001^[26]	Inactive: watch with monthly counts

Table C. Regimens and drugs: evidence and best fit

Regimen or drug	Best fit	Evidence	Main toxicity
BV-CHP	CD30-positive PTCL, all systemic ALCL	ECHELON-2: sALCL 5-year PFS 61% vs 48%	Neuropathy, neutropenia
CHOEP	Fit, ≤65, CD30-negative	Swedish registry: PFS HR 0.49 vs CHOP (≤60)	More myelosuppression than CHOP
CHOP	Older or less fit	Historical standard	Neutropenia, neuropathy, cardiotoxicity
Brentuximab vedotin alone	Relapsed CD30+ disease; frail sALCL	Relapsed sALCL: 73% response, 46% complete	Peripheral neuropathy
Crizotinib	Relapsed ALK+ ALCL	88% response in patients ≤21 years	See product information
Belinostat / pralatrexate / romidepsin	Relapsed PTCL, ALK− ALCL	Belinostat: 26% response (11% complete)	Belinostat: nausea (42%), fatigue, fever; cytopenias
Oral azacitidine (± romidepsin)	Relapsed TFH lymphoma	ORACLE: PFS 5.6 vs 2.8 months (not significant); combination 61% response (phase 2)	Cytopenias, GI effects
Autologous / allogeneic HCT	Responding relapse; selected first CR	Only route to long-term control after relapse	Transplant-related mortality (allo)

Table D. Managing problems during treatment

Problem	Prevent	Recognise	Act
Hypercalcaemia (ATLL)	Check calcium at diagnosis and during treatment	Confusion, thirst, constipation, kidney injury	IV fluids and calcium-lowering treatment; treat the lymphoma
HLH	High suspicion in febrile cytopenic patients	Fever, splenomegaly, ferritin very high, falling fibrinogen	Urgent specialist treatment alongside the lymphoma
Peripheral neuropathy (BV, vincristine)	Ask about tingling every cycle	Numbness, weakness, falls	Dose delay or reduction per protocol
Hepatitis B reactivation	HBsAg and anti-HBc before treatment	Rising ALT, HBV DNA	Antiviral prophylaxis; hepatology
Infections (incl. Strongyloides in ATLL)	Screen and treat Strongyloides before steroids in people from endemic areas; non-live vaccines	Fever, diarrhoea, chest signs	Early antibiotics; specialist advice
Tumour lysis	Hydration ± allopurinol in bulky disease	Rising potassium, phosphate, uric acid, creatinine	Monitor closely in the first days

07 Management algorithms

Five decision paths pull together sections 02–06.

Algorithm 1Suspected T-cell lymphoma: to an entity and a plan

Nodes with fever, rash or itching; a necrotic nasal mass; or abnormal T cells in blood → excision or deep biopsy before steroids; HLH screen if febrile and cytopenic

Name the entity

IHC: CD3, CD4, CD8, CD30, ALK, TFH markers, CD56, granzyme; EBER

CD30 strong → ALCL (ALK?)

TFH markers → AITL type

CD56 + EBER → NK/T

HTLV-1 → ATLL; TCL1 → T-PLL; none of these → PTCL-NOS

Stage and score

PET-CT; MRI nose/sinus for NK/T

Marrow if it changes management

IPI and PIT; ALK status

Skin-limited? → cutaneous module

Before cycle 1

HBV, HCV, HIV; calcium, LDH, ferritin

Echo; fertility

Transplant assessment for fit patients

Trial whenever available

All: expert haematopathology · CD30 reported on every case · plan the end-of-treatment decision at the start.

Algorithm 2PTCL-NOS, AITL and EATL: first line

Confirmed PTCL → CD30, age, fitness

CD30-positive (≥1%)

BV-CHP × 6

PET3: CR/PR → finish; SD/PD → refractory

ECHELON-2

CD30-negative, fit ≤65

CHOEP × 6

PET3 as above

Swedish registry: better PFS than CHOP

Older or less fit

CHOP × 6 (BV-CHP if CD30+)

PET3 as above

Goal: control with acceptable toxicity

End of treatment: stage I favourable → RT · fit, CR → observe or auto-HCT · single residual site → RT then auto-HCT · extensive residual → refractory pathway.

Algorithm 3Systemic ALCL by ALK status

Systemic ALCL (exclude cutaneous and breast implant-associated) → ALK, stage, fitness

ALK-positive

BV-CHP × 6

CR → observe (no transplant)

Limited PR → RT

3-year OS about 90%

ALK-negative

BV-CHP × 6

CR → observe or auto-HCT

Limited PR → RT then auto-HCT

3-year OS about 62%

Frail or children

Frail: BV alone

Children: trial or paediatric protocol

Limited stage, CR: observe or RT

All: interim PET after 3–4 cycles · extensive PR or progression → relapsed/refractory pathway.

Algorithm 4Relapsed or refractory PTCL and ALCL

Suspected relapse → biopsy (histology may change) → PET → transplant plan

sALCL

Late or BV-naïve → BV

Early / BV-refractory → ALK+: crizotinib; ALK−: belinostat, pralatrexate, romidepsin

Response → ALK+: auto-HCT (if none before); ALK−: auto, allo or observe

PET after 3 cycles

PTCL-NOS / AITL, fit

Combination salvage → HCT

Early or multiple relapse → newer agent

No prior auto, CR → auto-HCT

Prior auto or PR → allo-HCT

Not transplant-eligible

Sequential single agents (BV if CD30+, belinostat, pralatrexate, romidepsin, others)

Continue while benefiting

Median OS about 6 months without HCT: trials, palliative care

All: clinical trial first · infection prophylaxis and vaccines · early palliative care alongside treatment.

Algorithm 5Extranodal NK/T-cell lymphoma

NK/T-cell lymphoma confirmed (EBER+) → endoscopy, PET-CT, marrow, plasma EBV DNA → stage and fitness

Localised (IE / contiguous IIE)

CMT: concurrent CRT (DeVIC or cisplatin → VIDL) or sandwich (m-SMILE, P-GEMOX + RT)

CR → observe

Less than CR → HCT

Less fit: RT alone or GDP/MGAD + RT

Advanced or non-nasal

Asparaginase-based: m-SMILE, DDGP or P-GEMOX

CR or PR → HCT

Less fit: GDP ± RT to bulky sites

Relapsed or refractory

Salvage before transplant

Auto-HCT planned → PD-1 antibody

Allo-HCT planned → asparaginase-based if not recent

Transplant is the only proven cure

All: no anthracycline-based regimens · response by endoscopy, PET-CT and EBV DNA · experienced centre and trials.

08 Survivorship, follow-up & late effects

Figure 10. A simple follow-up rhythm, adapted from the UpToDate PTCL and sALCL treatment reviews. Individualise.

End of treatment: PET-CT; biopsy residual uptake if it would change management; record the transplant decision.
Years 1–2: relapses come early: visits every 3 months with history, examination, blood count and LDH; imaging for symptoms.
Late effects: anthracycline heart effects, neuropathy after BV or vincristine, radiation effects (nasal and sinus RT: dry mouth and eyes, hormone deficiencies), and transplant effects.
Infections: vaccinate with non-live vaccines; HBV prophylaxis as planned; prompt treatment of fever.

Figure 11. When relapses happen (UpToDate PTCL-NOS, initial and relapsed PTCL and sALCL reviews).

09 Landmark trials

Figure 12. How to read a survival curve (illustrative). Use the absolute gap at a fixed time and overall survival, not the median or PFS alone, when weighing benefit against toxicity and cost.

Figure 13. Landmark results as reported in the UpToDate PTCL and sALCL reviews.

ECHELON-2^[1]: BV-CHP vs CHOP in CD30-positive PTCL → better PFS and OS overall, driven by ALCL → BV-CHP standard for CD30-positive disease.
Swedish registry^[9] and DSHNHL^[10]: etoposide helps younger patients.
NLG-T-01^[11]: CHOEP then autologous transplant in first remission → the basis for consolidation in fit patients (no randomised proof).
BV phase 2^[12]: high response rates in relapsed ALCL, some long remissions.
BELIEF^[15] and PROPEL^[16]: modest single-agent activity in relapsed PTCL.
ORACLE^[7]: oral azacitidine in relapsed TFH lymphoma → longer median PFS, endpoint not met.

10 Practice pearls & pitfalls

A febrile patient with nodes, rash and high globulins may have AITL: biopsy a node rather than adding antibiotics or steroids.
Ask for CD30 on every PTCL: at 1% or more, BV-CHP is the first-line choice.
ALK-positive ALCL in a young patient is usually curable with chemotherapy alone; do not transplant in first remission.
A necrotic nasal mass: deep biopsies and EBER; superficial necrotic tissue misses NK/T lymphoma.
Hypercalcaemia with flower cells: test HTLV-1 (ATLL).
Very high lymphocyte count with skin infiltration and effusions in an older adult: think T-PLL; ask for TCL1.
Interim PET after three cycles: refractory disease needs a change of plan early.
Plan transplant work-up during induction for fit patients with PTCL-NOS, AITL or ALK-negative ALCL.
At relapse, biopsy: the histology may have changed, and EBV-driven B-cell lymphoma can arise in AITL.
Screen for HLH (ferritin, triglycerides, fibrinogen) in a febrile, cytopenic patient with T-cell lymphoma.

11 Case vignettes: lines of management

Six cases from the clinic.

Case 1AITL · CD30 negative · fit

Fever, rash and nodes treated as typhoid

58 years, manStage IVPIT 2

A 58-year-old shopkeeper has 6 weeks of fever, an itchy rash, generalised nodes and a palpable spleen. He received two courses of antibiotics for presumed typhoid. Haemoglobin 9.8 g/dL with a positive DAT; globulins high; LDH raised.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Diagnose
Excision of an axillary node: T follicular helper lymphoma, angioimmunoblastic type (PD-1, ICOS, CXCL13 positive; CD21 meshworks; EBV-positive B blasts); CD30 under 1%.
Stage
PET-CT: nodes above and below the diaphragm, spleen and marrow involved: stage IV; PIT 2 (raised LDH, marrow involvement).
Treat
Fit and under 65: CHOEP × 6 with steroids for the haemolysis; PET after 3 cycles: partial response → complete six; end PET: complete response.
Consolidate
Fit, advanced, in CR: autologous transplant discussed (observation is an option; no randomised proof); he chooses transplant.

Teaching points

AITL mimics infection and autoimmune disease: biopsy early.
CD30 under 1%: CHOEP if fit; BV-CHP if CD30 positive.
Decide consolidation at end-of-treatment PET.

See: Sections 02, 03 and 06, Algorithm 2.

Case 2ALK-positive ALCL · young

A 22-year-old with fast-growing neck nodes and bone pain

22 years, womanStage IVALK+

A 22-year-old student has neck nodes that doubled over 3 weeks, fever and pain in the right hip. LDH is raised.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Diagnose
Excision: sheets of large hallmark cells, CD30 strong (membrane and Golgi), ALK positive (nuclear and cytoplasmic: NPM::ALK). Systemic ALK-positive ALCL.
Stage
PET-CT: cervical and mediastinal nodes, right iliac bone: stage IV.
Treat
BV-CHP × 6 (ECHELON-2); fertility counselling before treatment; interim PET complete response.
After
End PET complete response: observation, no transplant. If she relapses: BV or crizotinib, then autologous transplant.

Teaching points

ALK-positive ALCL: young, curable; BV-CHP first line.
No transplant in first CR.
Relapse is still treatable: BV, crizotinib, transplant.

See: Sections 04 and 06, Algorithm 3.

Case 3ALK-negative ALCL · relapse

Relapse four months after BV-CHP

61 years, manEarly relapseBV-refractory

A 61-year-old with stage III ALK-negative ALCL achieved a partial response to BV-CHP. Four months later new nodes and fever appear.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Biopsy
Node excision: ALK-negative ALCL again, CD30 strong.
Classify
Early (under 6 months) and BV-refractory relapse.
Treat
Single-agent belinostat, pralatrexate or romidepsin rather than combination chemotherapy (UpToDate); PET after 3 cycles.
Plan
If CR: autologous or allogeneic transplant in a fit patient; otherwise continue while benefiting; clinical trial preferred.

Teaching points

Early or BV-refractory ALK-negative ALCL: newer single agents.
Transplant is the only route to long-term control.
Trials whenever possible.

See: Section 06 (relapse), Algorithm 4.

Case 4NK/T-cell lymphoma · nasal

A nasal ulcer called fungal sinusitis

44 years, manLocalisedEBER+

A 44-year-old farmer has 3 months of nasal blockage, foul discharge and a palatal ulcer. Two superficial biopsies showed "necrosis and acute inflammation"; antifungals did not help.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Diagnose
Deep biopsy under anaesthesia: angiocentric infiltrate with necrosis; CD56, cytoplasmic CD3, granzyme positive; EBER positive. Extranodal NK/T-cell lymphoma, nasal type.
Stage
MRI of nose and sinuses; PET-CT: disease confined to the nasal cavity and palate.
Treat
Localised and fit: combined-modality treatment (asparaginase- or platinum-based chemotherapy with RT, concurrent or sandwich) at an experienced centre; plasma EBV DNA, endoscopy and PET to assess response; CR → observe.
Teach
Superficial necrotic biopsies miss lymphoma; EBER is required for the diagnosis.

Teaching points

Deep biopsy and EBER for every destructive midline lesion.
No anthracycline regimens: asparaginase- or platinum-based chemotherapy with RT.
Nasal NK/T lymphoma is seen in India more than in the West.

See: Sections 02, 03 and 06 (NK/T).

Case 5ATLL · hypercalcaemia

Confusion, high calcium and abnormal lymphocytes

52 years, womanBorn in the CaribbeanHTLV-1+

A 52-year-old woman visiting family in Nellore is admitted with confusion, calcium 15 mg/dL, a white count of 38,000/µL with lobulated "flower" cells and a papular rash.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Stabilise
IV fluids and treatment of hypercalcaemia; check for Strongyloides before steroids.
Diagnose
Flow cytometry: CD4+, CD25+, CD7−; HTLV-1 antibodies positive and confirmed: adult T-cell leukaemia-lymphoma, acute variant.
Treat
Acute ATLL: VCAP-AMP-VECP (± mogamulizumab, avoided if allogeneic transplant is planned) or CHOP-like if unfit, with intrathecal prophylaxis; donor search for allogeneic transplant.
Family
HTLV-1 counselling for partner and children (breastfeeding and sexual transmission).

Teaching points

Hypercalcaemia with flower cells: ATLL until proven otherwise.
HTLV-1 testing separates ATLL from PTCL and Sézary syndrome.
Screen for Strongyloides.

See: Sections 02, 03 and 06 (ATLL).

Case 6PTCL-NOS · older

A 74-year-old with nodes and weight loss

74 years, manStage IIICD30 negative

A 74-year-old with diabetes and ischaemic heart disease (LVEF 50%) has 3 months of weight loss and generalised nodes.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Diagnose
Excision: PTCL-NOS (CD3+, CD5 lost, CD30 negative; no TFH profile; EBER negative).
Treat
Older, less fit, CD30-negative: CHOP × 6 with growth factor support; PET after 3 cycles.
After
Complete response at the end: observation (not a transplant candidate); limited residual site: RT.
At relapse
Sequential single agents and palliative care; median survival after relapse without transplant is short.

Teaching points

CHOP for older or less fit CD30-negative PTCL.
RT for limited residual disease when transplant is not possible.
Honest goals-of-care discussions at relapse.

See: Section 06, Algorithms 2 and 4.

12 References & guidelines

NCCN Guidelines: T-Cell Lymphomas (current version); ESMO lymphoma guideline (2025); WHO Classification, 5th edition, and the International Consensus Classification (2022); Lugano classification (2014).
Cross-checked in October 2026 against UpToDate topic reviews: PTCL-NOS diagnosis; T follicular helper cell lymphoma, angioimmunoblastic type; systemic ALCL diagnosis; extranodal NK/T-cell lymphoma diagnosis; ATLL diagnosis; T-PLL diagnosis; initial treatment of PTCL; initial treatment of systemic ALCL; relapsed or refractory PTCL; relapsed or refractory systemic ALCL; treatment of NK/T-cell lymphoma; treatment of ATLL; treatment of T-PLL. Citations from their reference lists. Indian data web-verified on 17 October 2026. Reviewed and approved by Dr. Haritha Chiramana, 17 October 2026.

Core trials and papers cited on this page (30)

Journal, year, volume and first page (or a PubMed search); each links to PubMed.

Numbered in order of first citation in the text

ECHELON-2: Horwitz S, O'Connor OA, Pro B, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2). Lancet 2019;393:229. PubMed First-line treatment
Lymphoma subtypes in India (Naresh 2000): Naresh KN, Srinivas V, Soman CS. Distribution of various subtypes of non-Hodgkin's lymphoma in India: a study of 2773 lymphomas. Ann Oncol 11 Suppl 1:S63. 2000. PubMed India
Lymphoma subtypes in Bihar (2020): Distribution of lymphoma subtypes in Bihar: analysis of 518 cases using the WHO classification (2017). J Lab Physicians 12:103. 2020. doi:10.1055/s-0040-1716633. PubMed India
ATLL diagnostic criteria (Shimoyama 1991): Shimoyama M. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. Br J Haematol 1991;79:428. PubMed Classification, diagnosis and prognosis
ATLL consensus (Cook 2019): Cook LB, Fuji S, Hermine O, et al. Revised adult T-cell leukemia-lymphoma international consensus meeting report. J Clin Oncol 2019;37:677. PubMed Classification, diagnosis and prognosis
T-PLL consensus criteria (Staber 2019): Staber PB, Herling M, Bellido M, et al. Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia. Blood 2019;134:1132. PubMed Classification, diagnosis and prognosis
ORACLE (Dupuis 2024): Dupuis J, et al. Oral azacitidine versus investigator's choice in relapsed or refractory T follicular helper cell lymphoma (ORACLE): an open-label randomised phase 3 study. Lancet Haematol 2024;11:e406. PubMed Relapsed or refractory disease
ECHELON-2 five-year (Horwitz 2022): Horwitz S, O'Connor OA, Pro B, et al. The ECHELON-2 trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive PTCL. Ann Oncol 2022;33:288. PubMed First-line treatment
Swedish registry CHOEP vs CHOP (Ellin 2014): Ellin F, Landström J, Jerkeman M, Relander T. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood 2014;124:1570. PubMed First-line treatment
German DSHNHL T-cell analysis (Schmitz 2010): Schmitz N, Trümper L, Ziepert M, et al. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of the German High-Grade NHL Study Group. Blood 2010;116:3418. PubMed First-line treatment
NLG-T-01 (d'Amore 2012): d'Amore F, Relander T, Lauritzsen GF, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol 2012;30:3093. PubMed First-line treatment
BV in relapsed sALCL (Pro 2012): Pro B, Advani R, Brice P, et al. Brentuximab vedotin in relapsed or refractory systemic anaplastic large-cell lymphoma: a phase II study. J Clin Oncol 2012;30:2190. PubMed Relapsed or refractory disease
BV in sALCL five-year (Pro 2017): Pro B, Advani R, Brice P, et al. Five-year results of brentuximab vedotin in relapsed or refractory systemic ALCL. Blood 2017;130:2709. PubMed Relapsed or refractory disease
Crizotinib in children (Mossé 2013): Mossé YP, Lim MS, Voss SD, et al. Crizotinib for paediatric refractory solid tumours or anaplastic large-cell lymphoma: a COG phase 1 consortium study. Lancet Oncol 2013;14:472. PubMed Relapsed or refractory disease
BELIEF belinostat (O'Connor 2015): O'Connor OA, Horwitz S, Masszi T, et al. Belinostat in relapsed or refractory PTCL: results of the pivotal phase II BELIEF study. J Clin Oncol 2015;33:2492. PubMed Relapsed or refractory disease
PROPEL pralatrexate (O'Connor 2011): O'Connor OA, Pro B, Pinter-Brown L, et al. Pralatrexate in relapsed or refractory PTCL: results from the pivotal PROPEL study. J Clin Oncol 2011;29:1182. PubMed Relapsed or refractory disease
Oral azacitidine + romidepsin (Falchi 2021): Falchi L, Ma H, Klein S, et al. Combined oral 5-azacytidine and romidepsin are highly effective in PTCL: a multicenter phase 2 study. Blood 2021;137:2161. PubMed Relapsed or refractory disease
PINK (Kim 2016): Kim SJ, Yoon DH, Jaccard A, et al. A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment (PINK). Lancet Oncol 2016;17:389. PubMed NK/T-cell lymphoma, ATLL and T-PLL treatment
JCOG0211 RT-DeVIC (Yamaguchi 2009): Yamaguchi M, Tobinai K, Oguchi M, et al. Phase I/II study of concurrent chemoradiotherapy for localized nasal NK/T-cell lymphoma: JCOG0211. J Clin Oncol 2009;27:5594. PubMed NK/T-cell lymphoma, ATLL and T-PLL treatment
CCRT then VIPD (Kim 2009): Kim SJ, Kim K, Kim BS, et al. Concurrent radiation and weekly cisplatin followed by VIPD in stage IE to IIE nasal NK/T-cell lymphoma. J Clin Oncol 2009;27:6027. PubMed NK/T-cell lymphoma, ATLL and T-PLL treatment
SMILE (Yamaguchi 2011): Yamaguchi M, Kwong YL, Kim WS, et al. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed or refractory NK/T-cell lymphoma. J Clin Oncol 2011;29:4410. PubMed NK/T-cell lymphoma, ATLL and T-PLL treatment
Pembrolizumab in NK/T (Kwong 2017): Kwong YL, Chan TSY, Tan D, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing L-asparaginase. Blood 2017;129:2437. PubMed NK/T-cell lymphoma, ATLL and T-PLL treatment
JCOG9801 VCAP-AMP-VECP (Tsukasaki 2007): Tsukasaki K, Utsunomiya A, Fukuda H, et al. VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: JCOG9801. J Clin Oncol 2007;25:5458. PubMed NK/T-cell lymphoma, ATLL and T-PLL treatment
Mogamulizumab + mLSG15 (Ishida 2015): Ishida T, Jo T, Takemoto S, et al. Dose-intensified chemotherapy alone or with mogamulizumab in newly diagnosed aggressive ATL: a randomized phase II study. Br J Haematol 2015;169:672. PubMed NK/T-cell lymphoma, ATLL and T-PLL treatment
AZT + interferon meta-analysis (Bazarbachi 2010): Bazarbachi A, Plumelle Y, Carlos Ramos J, et al. Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma. J Clin Oncol 2010;28:4177. PubMed NK/T-cell lymphoma, ATLL and T-PLL treatment
Alemtuzumab in T-PLL (Dearden 2001): Dearden CE, Matutes E, Cazin B, et al. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood 2001;98:1721. PubMed NK/T-cell lymphoma, ATLL and T-PLL treatment

Further reading (not cited in the text above)

WHO 5th edition lymphoid (Alaggio 2022): Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the WHO Classification of Haematolymphoid Tumours: lymphoid neoplasms. Leukemia 2022;36:1720. PubMed Classification, diagnosis and prognosis
International Consensus Classification (Campo 2022): Campo E, Jaffe ES, Cook JR, et al. The International Consensus Classification of mature lymphoid neoplasms. Blood 2022;140:1229. PubMed Classification, diagnosis and prognosis
International T-cell Project (Vose 2008): Vose J, Armitage J, Weisenburger D. International peripheral T-cell and NK/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 2008;26:4124. PubMed Classification, diagnosis and prognosis
PIT (Gallamini 2004): Gallamini A, Stelitano C, Calvi R, et al. Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model. Blood 2004;103:2474. PubMed Classification, diagnosis and prognosis

How to cite this page

VancouverChiramana H. T-cell Lymphomas: a mini review for clinicians. Oncology Knowledge Hub [Internet]. Nellore (India): drharitha.co.in; 2026 [updated 2026 Oct 17; cited year month day]. Available from: https://drharitha.co.in/professionals/t-cell-lymphomas

APA 7Chiramana, H. (2026, October 17). T-cell Lymphomas: A mini review for clinicians. Oncology Knowledge Hub. Retrieved Month Day, Year, from https://drharitha.co.in/professionals/t-cell-lymphomas

Free to use and share for education with attribution; please do not alter or use commercially (CC BY-NC-ND 4.0). Replace the italic parts with the date you accessed the page.

Educational summary for health professionals, written in our own words from current guidelines and primary trials. No drug doses are given. Hodgkin, aggressive B-cell and indolent B-cell lymphomas are parts 1–3 and cutaneous lymphomas part 5; leukaemias will follow as a separate module. Verify current guidelines, Indian regulatory approvals and individual patient factors before treatment decisions.

Written by Dr. Haritha ChiramanaSenior Medical Oncologist & Hemato-Oncologist · MD, DM (Medical Oncology) · C.R. Reddy Cancer Center, Nellore, Andhra Pradesh, India

Medically reviewed by Dr. Haritha Chiramana on 17 October 2026. This page is general education and cannot replace an individual consultation.