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.
