Lymphoma
AJ Winer
Background
- Definition: malignant disorder of lymphoid cells that reside mostly in lymphoid tissues
- Generally categorized as Hodgkin lymphoma (HL) / non-Hodgkin lymphoma (NHL)
Clinical Manifestations
Classically characterized by lymphadenopathy (usually nontender) & constitutional “B” symptoms (fevers, drenching sweats, weight loss).
- HL (10%): superficial nodal disease with orderly, anatomic spread to adjacent nodes
- NHL (90%): diffuse nodal +/- extranodal disease with non-contiguous spread
Diagnostic and staging evaluation
- Physical Exam:
- LN (painless, firm, fixed, >1cm), head and neck, tonsils, axilla, testes, liver, spleen
- Lab tests:
- CBC, CMP, LDH, uric acid, phosphorus
- Consider HBV panel, HCV, HIV, EBV, Quant gold, treponemal Ab, ANA
- Imaging:
- CT chest, abdomen, pelvis; most will eventually need PET-CT to assess extent of disease and guide bx/therapy; MRI brain if neuro symptoms
- Pathology: diagnosis requires tissue (excisional preferred to see tissue architecture):
- Excisional lymph node biopsy: Surgical Oncology, EGS, or ENT consult
- Core biopsy: CT guided procedure consult
- Of note, steroids may impact value of biopsy results
- LP: consider for NHL with high risk of CNS involvement or presence of neurological sx
- Risk factors: Burkitt, lymphoblastic, testicular involvement, double/triple hit
- Multiple LPs may be required to diagnose CNS lymphoma
- Staging: Lugano Classification
- I. 1 LN region or single extra lymphatic organ/site without nodal involvement
- II. >2 LN regions, same side of diaphragm
- III. LN regions on both sides of diaphragm
- IV. Disseminated disease w/ 1+ extra lymphatic organ
General Management
- ECG and TTE to establish pre-chemo cardiac function—many regimens with anthracyclines
- Daily labs: CBC, TLS, LDH - TLS prophylaxis: mIVF, allopurinol
- Treatment: see below
HL vs. NHL
Features |
HL (10%) |
NHL (90%) |
|---|---|---|
| Epidemiology | Bimodal distribution: 15-35 years and >50 years; M>F | Average 65 years, M>F, 85-90% B-cell |
| Histology | CD15+, CD30+ (Reed Sternberg cells “owl eyes”) | Varies, but majority involve B cells (can also be T cell, NK cell) |
| Associations | EBV in immunocompromised | Associated with immunodeficiency (HIV, post-transplant), autoimmune disease, infection (EBV, HTLV-1, H pylori, HCV, Borrelia, C psittacosis, Coxiella) |
| Lymph Node Pattern | Contiguous LN spread | Noncontiguous LN spread |
| Subtypes |
|
DLBCL, Follicular, MALT, Mantle cell, Burkitt, Hairy cell, Marginal Zone, TCell (mycosis fungoides/Sezary), CLL/SLL, other |
| Prognosis |
|
|
| Common Treatment Regimens | ABVD + radiation (early stage), Nivo-AVD (advanced stage) | R-CHOP, R-EPOCH, Hyper-CVAD, HDMTX + R |
Common Chemotherapy Regimens for Lymphoma
Regimen |
Components |
Use |
|---|---|---|
| R-CHOP | rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone | NHL |
| R-EPOCH | etoposide plus the drugs above (inpatient administration with 4 days continuous infusion followed by pushes of chemotherapy on Day 5) | NHL (Double/Triple hit) |
| Hyper-CVAD | cyclophosphamide, vincristine, doxorubicin, and dexamethasone (requires inpatient admission given BID dosing of cyclophosphamide and continuous mesna to prevent hemorrhagic cystitis) | NHL |
| HD-MTX + R | high dose methotrexate + rituximab (requires inpatient admission to follow MTX clearance and alkalize urine with continuous bicarb infusion) | Primary CNS Lymphoma |
| ABVD | doxorubicin, bleomycin, vinblastine, dacarbazine | HL |
| Nivo-AVD | Nivolumab, doxorubicin, vinblastine, dacarbazine | HL |
Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
Definition
- CLL is a disease of monoclonal, functionally incompetent mature B lymphocytes
- CLL and SLL are different manifestations of the same disease and are distinguished by the distribution of lymphocytes. CLL is mostly in peripheral blood whereas SLL is mostly in lymph nodes and patients often present with both. Treatment plans are identical.
- CLL: >5000/uL malignant cells on peripheral smear
- SLL: <5000/uL cells + LAN +/- splenomegaly
Epidemiology
- 15,000 new cases per year; median age at dx is 71
Manifestations
- Most often asymptomatic, identified by lymphocytosis on CBC.
- 10-20% have B symptoms, LAN in 80%, HSM in 50%, AIHA in 10%, 1-2% have ITP.
- Increased susceptibility to infections due to hypogammaglobulinemia from abnl B-cells
- 5% patients develop aggressive transformation into high-grade lymphoma (Richter’s)
Diagnostic Evaluation
- CBC with diff (B-cell count), peripheral smear (lymphocytosis, smudge cells)
- Flow cytometry: clonality with dim surface Ig CD5+, CD19+, CD20+, CD23+
- Bone marrow biopsy is not required for diagnosis but may be normo or hypercellular
- Genetics: del 11q22-23 and del(17p) are unfavorable; trisomy 12 is neutral; del 13q14 and mutation IGHV is favorable
Staging and Prognosis
Risk Status |
Modified Rai System |
Binet System |
|---|---|---|
| Low Risk | Rai Stage 0: Lymphocytosis | Binet Stage A: <3 involved nodal areas |
| Intermediate Risk | Rai Stage I: Lymphocytosis + LAN Rai Stage II: Lymphocytosis + Splenomegaly and/or hepatomegaly |
Binet Stage B: >/=3 involved nodal areas |
| High Risk | Rai Stage III: Lymphocytosis + Hgb <11 g/dL Rai Stage IV: Lymphocytosis + Plt <10 x 104 g/uL |
Binet Stage C: Hgb <10 g/dL and/or Plt <10 x 104 g/uL |
Treatment
- Observation unless “active disease” (B symptoms, symptomatic adenopathy, cytopenias, lymphocyte doubling time < 6 months)
- First line: if no del(17p)/TP53 use BTK inhibitor until disease progression (indefinite), venetoclax+obinutuzumab (fixed duration 12 months), or BTK inhibitor + venetoclax (fixed duration 14 months); if + del(17p)/TP53, use BTK inhibitor (longest duration of response) or venetoclax + obinutuzumab (shorter duration of response
- HSCT is the only curative treatment but rarely used given excellent prognosis with current treatments