T CELL LYMPHOMA Flashcards
Preferred first line therapy for ALCL
Brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, and prednisone)
Other recommended regimens:
* CHOP
* CHOEP
* Dose-adjusted EPOCH
Preferred first line therapy for PTCL-NOS; EATL; MEITL; AITL; nodal PTCL, TFH; and FTCL
- Brentuximab vedotin + CHP for CD30+ histologies
- CHOEP
- CHOP
- Dose-adjusted EPOCH
Newcastle Regimen studied only in patients with EATL
CHOP followed by IVE (ifosfamide, etoposide, and epirubicin)
First line consolidation
Consider consolidation with autologous HCT
An uncommon and emerging PTCL most frequently arising around a textured surface breast implant or in a patient with a history of a textured surface device
BREAST IMPLANT-ASSOCIATED ANAPLASTIC LARGE CELL LYMPHOMA (BIA-ALCL)
Common presentation of BIA-ALCL
Delayed periprosthetic effusion and breast asymmetry occurring greater than 1 year (average, 7–9 years) after implantation
Treatment of BIA-ALCL
- Total capsulectomy and excision of associated mass with biopsy of suspicious node(s), explantation
- Removal of contralateral implant
- Consultation with surgical oncologist recommended for patients with preoperative tumor mass
Preferred Systemic Therapy for BIA-ALCL
- Brentuximab vedotin
- Brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, and prednisone)
- CHOP
- CHOEP
- Dose-adjusted EPOCH
An indolent T-cell lymphoproliferative disorder (LPD) of the mature cytotoxic lymphocytes of effector memory cell phenotype.
Most cases have an indolent and non-progressive clinical course, and moderate to severe autoimmune neutropenia is a frequent laboratory abnormality.
T-CELL LARGE GRANULAR LYMPHOCYTIC LEUKEMIA (LGLL)
Thrombocytopenia and anemia are less common and may accompany neutropenia leading to bilineage or trilineage cytopenias.
In the majority of patients with LGLL is
diagnosed concurrently with rheumatologic disease:
- Rheumatoid arthritis [RA]
- Systemic lupus erythematosus [SLE])
- Crohn’s disease
- Sjogren’s syndrome
- Psoriatic arthritis.
Morphologic features of LGLL
Large granular lymphocytes characterized by reniform or round nucleus, moderate to copious cytoplasm with prominent azurophilic granules) in the peripheral blood and the bone marrow of the patients (>2000/uL)
Persistence (>6 months)
Exclusion of other potential conditions or illnesses where LGL is part of the pathologic process (ie, viral infections, other malignancies, rheumatologic disease)
Typical immunophenotype for T-LGLL:
CD3+, CD8+, CD16+, CD57+, CD56+/-, CD28, CD5 dim, and/or CD7 dim, CD45RA+, CD62L-, TCRαβ+, TIA1+, granzyme B+, or granzyme M+
30% of LGLL cases has this mutation
STAT3 mutations affecting the SH2 domain
STAT5B SH2 mutations have also been reported.
Indications for treatment in T-Cell Large Granular Lymphocytic Leukemia
- ANC <0.5 x 109/L
- Hemoglobin <10 g/dL or need for red blood cell (RBC) transfusion
- Platelets <50 x 109/L
- Autoimmune diseases with T-LGLLs requiring therapy
- Symptomatic splenomegaly
- Severe B symptoms
- Pulmonary artery hypertension secondary to LGLL
- ANC <1500 with documented T-LGLL and recurrent infections
May be beneficial in patients with autoimmune disease
Methotrexate with or without steroids
May be used as a first- or second-line option in patients with anemia
Cyclophosphamide or cyclosporine
Treatment Response in LGLL
CR
- Hgb >12 g/dL
- ANC >1.5 x 109/L
- Platelet >150 x 109/L
- Resolution of lymphocytosis (<4 x 109/L), and
- Circulating LGLL counts within normal range (<0.5 x 109/L)
Treatment Response in LGLL
PR
- Hgb >8 g/dL
- ANC >0.5 x 109/L
- Platelet >50 x 109/L
- Absence of transfusions
Purine analogues used in LGLL
Pentostatin, cladribine, and fludarabine
First line therapy for T-LGLL
- Low-dose methotrexate
- Low-dose methotrexate + corticosteroid
- Cyclophosphamide
- Cyclophosphamide + corticosteroid
- Cyclosporine
- Cyclosporine + corticosteroid
Second-line Therapy for Progressive or refractory T-LGLL
- Ruxolitinib
- Pentostatin
- Cladribine
- Fludarabine
- Alemtuzumab
Typical immunophenotype of T-Cell Prolymphocytic Leukemia
CD1a-, TdT-, CD2+, sCD3+/-, cCD3+/-, CD5+, CD7++, CD52++, TCRαß+, CD4+/CD8- (65%), CD4+/CD8+ (21%), CD4-/CD8+ (13%).
DIAGNOSTIC CRITERIA FOR T-CELL PROLYMPHOCYTIC LEUKEMIA (T-PLL)
Major Criteria
* >5 x109/L cells of T-PLL phenotype in peripheral blood or bone marrow
* T-cell clonality (by PCR for TRB/TRG, or by flow cytometry)
* Abnormalities of 14q32 or Xq28 OR expression of TCL1A/B, or MTCP1
Minor Criteria (at least 1 required)
* Abnormalities involving chromosome 11 (11q22.3; ATM)
* Abnormalities in chromosome 8: idic(8)(p11), t(8;8), trisomy 8q
* Abnormalities in chromosomes 5, 12, 13, 22, or complex karyotype
* Involvement of T-PLL–specific site (eg, splenomegaly, effusions)
The diagnosis of T-PLL is established if all 3 major criteria are met or if the first 2 major criteria and 1 minor criterion are met.
Test used in distinguishing T-PLL from Sézary syndrome or ATLL
TCL1 and TRA Translocation
Most T-PLL have an inversion or translocation of chromosome 14 with breakpoints in the long arm at q11 and q32 [inv(14)(q11q32) and
t(14;14)(q11;q32)].
These translocations and inversions cause gene overexpression due to juxtaposition with TCRα or TCRß regulatory elements and activate the oncogenes TCL1A and MTCP1-B1.
Preferred regimen for T-Cell Prolymphocytic Leukemia
- Clinical trial
- Alemtuzumab (IV) alone
Other recommended regimens
* FMC (fludarabine, mitoxantrone, cyclophosphamide) followed by alemtuzumab (IV) in selected patients
* Alemtuzumab (IV) and pentostatin in selected patients
Preferred regimen as Second-line or subsequent therapy for T-Cell Prolymphocytic Leukemia
- Clinical trial
- Pentostatin
Typical morphologic features of ATLL cells
(“flower cells”) have distinctly polylobated nuclei with homogeneous and condensed chromatin, small or absent nucleoli, and agranular and basophilic cytoplasm
Adult T-Cell Leukemia/Lymphoma
Presence of ______ % atypical cells by morphology in peripheral blood is required for diagnosis of blood involvement in the absence of other criteria
≥5%
Typical immunophenotype of ATLL:
CD2+, CD3+, CD4+, CD5+, CD7-, CD8-, CD25+, CD30-/+, TCRαβ+
First-line therapy for Symptomatic Smoldering ATLL
- Clinical trial
- Skin-directed therapies as clinically indicated
- Zidovudine and interferon
Chronic ATLL
- Low Risk:
- Intermediate risk:
- High risk:
Chronic ATLL
- Low Risk: (sIL-2R <1000 U/mL)
- Intermediate risk: (sIL- 2R 1000-6000 U/mL)
- High risk:(elevated LDH, low albumin, high BUN, sIL-2R >6000 U/mL)
MODIFIED PROGNOSTIC INDEX FOR AGGRESSIVE ATLL
- Clinical subtype of acute ATLL
- CRP level ≥2.5 mg/dL
- ECOG PS 2–4
- sIL-2R >5,000 U/mL
- Adjusted Ca level ≥12 mg/dL
- Low 0–1
- Intermediate 2–3
- High 4–5
Preferred initial therapy for ATLL
- Clinical trial
- Brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, and prednisone) for CD30+ cases
- Dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)
- Zidovudine and interferon (acute, chronic, and symptomatic smoldering subtypes)
Useful in those unable to tolerate intensive regimen or non-CD30 expressing ATLL
CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
A rare, systemic, mature T-cell malignancy most often characterized by spleen, liver, and bone marrow involvement and an aggressive clinical course.
Bulky lymphadenopathy is uncommon.
Hepatosplenic T-Cell Lymphoma
- Median age of 35 years
- Up to 20% of cases arise in chronic immune suppression
Typical immunophenotype of HTCL:
CD3+, generally TCRδ+ and TCRβ- (GM3 positive, βF-1 negative), CD4 -, CD8-/+, CD56 +/-, CD5-.
Preferred regimen for HTCL
- Clinical trial (preferred)
- ICE
CHOP is not adequate therapy
Typical NK-cell immunophenotype:
CD20-, CD2+, cCD3ɛ+ (surface CD3-), CD4-, CD5-, CD7-/+, CD8-/+, CD43+, CD45RO+, CD56+, TCRαß-, TCRγδ-, EBER+.
TCR and Ig genes are germline (NK lineage).
Cytotoxic granule proteins (TIA1, perforin, granzyme B) are usually expressed.
Typical T-cell immunophenotype:
CD2+, sCD3+, cCD3e+, CD4, CD5, CD7, CD8 variable, CD56+/-, EBER+, TCRαß+ or TCRγδ+, cytotoxic granule proteins +.
TCR genes are clonally rearranged.
PROGNOSTIC INDEX OF NATURAL KILLER LYMPHOMA (PINK)
- Age >60 y
- Stage III or IV disease
- Distant lymph-node involvement
- Non-nasal type disease
Low 0
Intermediate 1
High ≥2
PROGNOSTIC INDEX OF NATURAL KILLER CELL LYMPHOMA WITH EPSTEIN-BARR VIRUS DNA (PINK-E)
- Age >60 y
- Stage III or IV disease
- Distant lymph-node involvement
- Non-nasal type disease
- Epstein-Barr virus DNA
Low 0–1
Intermediate 2
High ≥3
Preferred chemotherapy for ENKL
Asparaginase-based
* Modified SMILE (steroid [dexamethasone], methotrexate, ifosfamide, pegaspargase,e and etoposide) x 4–6 cycles for advanced stage
* P-GEMOX (gemcitabine, pegaspargase, and oxaliplatin)
* DDGP (dexamethasone, cisplatin, gemcitabine, and pegaspargase) x 3–6 cycles
Preferred chemotherapy for R/R ENKL
- Clinical trial
- Pembrolizumab
- Nivolumab
A rare leukemic form of an NK cell neoplasm with an aggressive clinical course
Predominantly occurs in younger patients with a median age of 40 years, frequently presenting with B symptoms and concomitant HLH
Patients can also have hepatosplenomegaly and lymphadenopathy
In comparison to ENKL, ANKL does not usually have nasal or skin involvement
AGGRESSIVE NK-CELL LEUKEMIA (ANKL)
ALK expression is often associated with what translocation
t(2;5)(p23;q35)
Leading to the fusion of NPM1 to ALK and resulting in a chimeric protein
Test to support diagnosis of AITL versus other PTCLs
TET2/IDH1/IDH2/RHOA/DNMT3A Mutations
High incidence of somatic mutations in IDH2 and TET2 genes has been identified in AITLs.
This pathway has been preliminarily associated with higher rates of response to histone deacetylase (HDAC) inhibitors and other epigenetic modifiers.
Clinical trials of this approach are currently ongoing.
Syndrome of extreme immune activation resulting in life-threatening inflammation
Hemophagocytic Lymphohistiocytosis (HLH)
HLH in adults is often associated with an underlying T-cell lymphoma.
Clinical signs and symptoms of HLH may include: (these may overlap with features of underlying lymphoma):
- Fever
- Hepatosplenomegaly
- Cytopenias (affecting 2 of 3 lineages in the peripheral blood)
◊ Hemoglobin <9 g/dL
◊ Platelets <100 x 103/mL
◊ Neutrophils <1 x 103/mL - Hypertriglyceridemia and/or hypofibrinogenemia
◊ Fasting triglycerides >3.0 mmol/L (ie, >265 mg/dL)
◊ Fibrinogen <1.5 g/L - Hemophagocytosis in bone marrow or spleen or lymph nodes
- Ferritin >500 ng/mL
- sIL-2R (also known as soluble CD25 [sCD25]) >2400 U/mL
- Elevated transaminases and bilirubin
- Elevated LDH
- Elevated D-dimer
- Elevated CSF cells and/or protein
Optimized HLH inflammatory (OHI) index
Simplify the diagnosis of HLH in patients with hematologic malignancies
- sCD25 (>3900 U/mL) and
- Ferritin (>1000 ng/mL)]
Management of HLH
- Treatment of the underlying T-cell lymphoma with preference for etoposide- and steroid-containing regimens.
- Start with HLH-directed therapy if cytopenias preclude standard anti-lymphoma therapy, and then initiate standard anti-lymphoma therapy when cytopenias improve.
- Antiviral therapy
