Flashcards in T Cell Lymphoma Deck (45):
What is the immunophenotype of AITL?
+/- BCL6, CD10
May lose a subset of pan T-cell Antigens
=CD2, CD3, CD5, CD7
What are the 2 types of Enteropathy-associated T ell lymphoma
- Typically express CD3, but do not express CD4
- Mostly CD8-
- Large cells within tumor infiltrate CD30+
- TCR Beta gene is clonally rearranged.
- Many with a HLA haplotype-associated with celiac disease
- 50-60% have complex segmental amplification of the 9q34 region
- CD8+, CD56+, TCR Gamma-delta+
- often with application of c-myc 8q24
Most common T Cell Lymphoma?
EN NKT Cell
What are the common cytogenetic changes typical/diagnostic of AITL?
Trisomy 3, 5
Additional X chromosome
What is the Follicular Denditrtic Cell Network?
CD21, CD23, CD35
Usually present in AITL
What are the differentials for AITL?
EBV+ DLBCL, NOS
How is AITL distinguished from other PTCLs?
FDC mesh work present (CD21, CD23, CD35)
Tell me about Breast implant associated ALCL
Described as development of ALCL around the implant (involving the fibrous capsule and/or Serena only)
Natural Hx appears generally more favorable with surgical removal to he implant alone as adequate therapy for most
Rare cases with parenchymal breast or nodal involvement may have an aggressive course more in line with systemic ALK-positive ALCL
Optimal treatment not well-defined, management should be individualized
What is the Newcastle regimen?
CHOP --> IVE (Ifosfamide, Etoposide, epirubicin), alternating with intermediate dose MTX
- used only in patients with EATL
- includes HSCT
What are the options for first line treatment of PTCL?
No standard treatment
Clinical trial is an option
If ALCL, ALK+,
- to consider with high-dose therapy and stem cell rescue
- patients with low IPI ALCL, ALK+ disease in remission do not need Consolidative transplant
What are the possible 2nd-line treatment options for TCL that are single agents?
Brentuximab for CD30+ PTCL
What are the available combination regimens for PTCL?
DHAP (Dexa, CDDP, Cytarabine)
ESHAP(Etoposide, Methylprednisolone, Cytarabine, CDDP)
GDP (Gem, Dexa, CDDP)
GemOx (Gem, Ox)
ICE (Ifosfamide, Carboplatin, Etoposide)
Give me examples of primary nodal PTCLs
ALCL - ALK+/ALK-
Give me examples of primary Extranodal PTCL
Enteropathy-associated TCell lymphoma (EATL)
Extranodal-natural killer/T-Cell lymphoma (ENKTCL)
Hepatosplenic T cell lymphoma (HSTCL)
What is the general epidemiology of PTCLs?
Uncommon and heterogenous
Originate from post-thymic (peripheral) T cells or mature NK Cells
10-15% of all NHL
Male: Female 2:1
Median age 6th to 7th decade
Both sex & age patterns vary according to different subtypes.
Some association with certain conditions:
EBV - ENKTCL
Celiac disease - EATL
Crohn's - HSTCL
What suggests that a given T-cell population is neoplastic?
2) Aberrant T-Cell phenotype
3) Clonally rearranged T-Cell receptor (TCR) genes (alpha-beta vs gamma-delta)
What is the presumed cell of origin for:
1) PTCL-NOS : variable, mostly T-helper cell
2) AITL : Follicular T-helper
3) ALCL : Cytotoxic T cell
What suggests a cytotoxic profile?
TIA1, granzyme B, perforin
What is the difference in immunophenotype between EATL Type I and II?
EATL Type I = CD8+/CD56-
EATL Type II = CD8-/CD56+
Type II is also not a/w pre-existing enteropathy
What is the immunophenotype of ALCL?
CD30+, PAX5-, EMA+
If t(2:5) present, ALK+
What are the staging blood tests required?
Routine blood chemistry
LDH, Uric acid
HIV, HTLV-1, Hep B/C
What is the management of HSTCL?
One of the worst prognoses. 5y OS and FFS
What is the treatment for ENKTCL?
1st line - L-asparaginase containing regimens eg. SMILE and AspaMetDex
CHOP or CHOP-like tx not effective
Localized disease = Addition of RT to chemo
Stage I/II = concurrent = sequential
- RT ~>50Gy, but if radiosensitizers used, 40Gy
CNS prophylaxis not recommended
HDCT --> transplant controversial
Stage III/IV: L-asparaginase-containing regimens preferred. IF CR, then HDC with HSCT
After anthracycilne-based --> L-asparagine see regimens --> gemcitabine-based --> auto/also transplant
What are the treatment options for EATL?
Outcome after standard CHOP poor
If can tolerate more aggressive chemo, IVE/MTX = Ifosfamide/vincristine/Etoposide/MTX
- this is followed by autoSCT.
Relapse: no evidence. Consider allo.
What is the treatment for nodal PTCL?
- those 60yo or younger. With older patients, toxicity is a limiting factor.
- consolidated by AutoSCT
2) localized Stage I disease: shortened chemo, followed by local RT
3) Brentuzimab in relapse
- ORR 86% with CR rate 60% and median response duration 12.6m
- can serve as a bridge to transplant as well
What is the most common T Cell Lymphoma?
In Asia, PTCL-NOS and NKTL are almost as equally common
What is the average 5y OS for the TCell Lymphomas
1) Cutaneous ALCL
3) Nasal NK
6) Extranasal NKT
1) Cutaneous ALCL 90%
2) ALK+ ALCL 60%
3) Nasal NKT 40%
4) PTCL-NOS 35%
5) ALK-ALCL 35%
6) Extranasal NKT 10%
Tell me about AITL
1) Age: middle-aged to elderly
2) P/w: generalized LAN, HSM, prominent systemic symptoms
3) Bloods: Polyclonal Ig increase, hemolytic anemia, cold agglutinin, cryoglobulinemia
4) Morphology: polymorphic infiltrate of small-medium lymphocyte with clear cytoplasm. Arborizing high endothelial venules. Proliferation of Follicular dendritic cells
5) IHC: CD4+, loss of pan TCell Ag uncommon. CD20+, CD10+, BCL6+
Tell me about PTCL-NOS
1) Age: 60yo
2) P/w: nodal involvement. Can be a combination of nodal and Extranodal involvement. Majority p/w advanced disease
3) Morphology: inter follicular, diffuse infiltrates. Medium-large cells, multilobulated forms with prominent nucleoli and focal necrosis.
4) IHC : CD2, D3, CD5, CD7,
- most single CD4+ or less often CD8+
- sometimes CD4- CD8-, rarely both positive
- >85% express TCR alpha-beta.
What are the different patterns of AITL?
Pattern 1: Hyperplastic GC
Pattern 2: Regressed GC
Pattern 3: Effaced GC
Patterns 2 &3 a/w with worse survival outcome.
What are the common molecular aberrations in AITL?
TET2 mutation 80%
DNMT3A mutation 30%
IDH2 mutation 20%
RHOA mutation 70%
Tell me about ALCL
1) Age: ALK+ most frequent in 1st 3 decades with male predominance
- ALK+ with better prognosis
2) p/w: mostly with advanced stage and B symptoms
3) Morhpology: Large cells, horse-shoe or kidney-shaped nuclei. Donut cells tat appear to have cytoplasmic inclusions
- ALK+ ALCL: EMA+ CD3-
Nasal cavity + other regions of upper aero digestive tract, skin, GI, Testis, soft tissue
Aggressive tumor with poor prognosis
Morphology : small--> Moderate --> Large cells
- CD2+ ,surface CD3-, cytoplasmic CD3+, CD56+
- CD4, CD8, TCR alpha-beta, TCR gamma-delta negative
- TIA-1, granzyme B, Perforin usually positive
- EBER +
What are the first-line therapeutic options available for ALCL, ALK+?
Low IPI ALCL, ALK+ disease in remission, do not need Consolidative therapy.
What are the therapeutic options available for other T Cell lymphoma (excluding ALCL ALK+)
CHOP--> IVE (Ifosfamide, Etoposide, epirubcin) alternating with intermediate dose methotrexate
>> known as the Newcastle regimen, but studied only in EATL patients
HyperCVAD alternating with HD MTX/Cytarabine
Consider consolidation with HD Therapy and stem cell rescue
What is Denileukin diffitox?
Denileukin Diffitox is a fusion protein that combines fragments of diphtheria toxin with IL2.
IL2 domain targets tumor cells bearing IL2 receptor.
What are the risks a/w Denileukin Diffitox?
What is Denileukin Diffitox best used for?
AITL. ORR 80%
What is the BENTLY trial?
Damaj JCO 2013
Ph II R/R TCL,
What are the FDA approved agents for R/R PTCL?
Tell me about Romidepsin
Coiffier JCO 2012
2 prior lines of treatment
ORR 25% with CR 15%
Median duration of response 17m
Med PFS 4m
Tell me about pralatrexate
It is an anti-folate agent
Binds DHFR and presents dihydrofolate coversion to tetrahydrofolate.
Tetrahydrofolate is required for purine/pyrimidine and aa synthesis.
Why does conventional chemotherapy not work well in PTCL?
1) Higher rate of primary refractory disease
2) Higher rate of relapse disease
3) Lack of efficacy of anthracyclines
What is the NKT cell Lymphoma prognostic index?
Serum LDH > Normal
LN - N1 to N3, not M1
Ann Arbor Stage IV
No of risk factors
Low - 0
Low intermediate - 1
High intermediate - 2
High - 3 or 4