“If this blog helped you out, don’t keep it to yourself—share the link on your socials!” 👍 “Like what you read? Spread the love and share this blog on your social media.” 👍 “Found this useful? Hit share and let your friends know too!” 👍 “If you enjoyed this post, please share the URL with your friends online.” 👍 “Sharing is caring—drop this link on your social media if it helped you.”

Monday, August 11, 2025

Non-Hodgkin lymphoma


Introduction
Non-Hodgkin lymphoma (NHL) is a heterogeneous group of malignant lymphoid neoplasms that arise from B cells, T cells, or natural killer (NK) cells at various stages of differentiation. Unlike Hodgkin lymphoma, NHL lacks the characteristic Reed–Sternberg cells and displays significant variability in clinical presentation, aggressiveness, and response to therapy. NHL is one of the most common hematologic malignancies worldwide, and its incidence increases with age.

Epidemiology

  • Accounts for ~90% of all lymphomas.

  • Global incidence: higher in developed countries, particularly in North America and Europe.

  • Median age at diagnosis: ~65 years.

  • Slight male predominance.

  • Increased incidence in immunocompromised populations (HIV/AIDS, organ transplant recipients).

Etiology and Risk Factors

Infectious Agents

  • Epstein–Barr virus (EBV): associated with Burkitt lymphoma, post-transplant lymphoproliferative disorders.

  • Helicobacter pylori: linked to gastric mucosa-associated lymphoid tissue (MALT) lymphoma.

  • Human T-cell leukemia virus type 1 (HTLV-1): adult T-cell leukemia/lymphoma.

  • Hepatitis C virus (HCV): associated with some marginal zone and diffuse large B-cell lymphomas.

Immune System Dysfunction

  • Primary immunodeficiency syndromes.

  • Acquired immunosuppression (e.g., post-transplant).

  • Autoimmune diseases (e.g., rheumatoid arthritis, Sjögren’s syndrome, systemic lupus erythematosus).

Environmental and Chemical Exposure

  • Pesticides, herbicides, and solvents.

  • Radiation exposure.

Genetic and Molecular Abnormalities

  • Chromosomal translocations (e.g., t(14;18) in follicular lymphoma involving BCL2 overexpression).

  • Mutations affecting cell cycle regulation and apoptosis.

Classification

The World Health Organization (WHO) classification is based on cell of origin, morphology, immunophenotype, genetic features, and clinical behavior.

B-cell NHL (≈85–90% of cases)

  • Diffuse large B-cell lymphoma (DLBCL) – most common, aggressive.

  • Follicular lymphoma – indolent.

  • Mantle cell lymphoma.

  • Marginal zone lymphoma (including MALT lymphoma).

  • Burkitt lymphoma – highly aggressive.

  • Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.

T-cell and NK-cell NHL (≈10–15% of cases)

  • Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS).

  • Anaplastic large cell lymphoma (ALCL).

  • Angioimmunoblastic T-cell lymphoma.

  • Adult T-cell leukemia/lymphoma.

Pathophysiology

  • Malignant transformation of lymphocytes occurs due to genetic and epigenetic changes affecting cell proliferation, differentiation, and apoptosis.

  • Many NHL subtypes derive from germinal center or post-germinal center lymphocytes.

  • Oncogenic viruses, chronic antigenic stimulation, and genetic instability contribute to pathogenesis.

Clinical Presentation

Common Features

  • Painless lymphadenopathy (cervical, axillary, inguinal).

  • “B symptoms”: fever, night sweats, unintentional weight loss (>10% in 6 months).

  • Fatigue.

Extranodal Disease (more common in NHL than Hodgkin lymphoma)

  • Gastrointestinal tract: abdominal pain, bowel obstruction (e.g., MALT lymphoma).

  • Skin: cutaneous T-cell lymphoma.

  • Central nervous system: primary CNS lymphoma.

  • Bone marrow infiltration: cytopenias.

Aggressive vs. Indolent Forms

  • Aggressive: rapid onset, symptomatic, potentially curable (e.g., DLBCL).

  • Indolent: slow progression, often asymptomatic, may be observed until progression (e.g., follicular lymphoma).

Diagnosis

Histopathologic Confirmation

  • Excisional lymph node biopsy is preferred (preserves architecture).

  • Core needle biopsy if excisional not feasible.

Immunophenotyping

  • Flow cytometry or immunohistochemistry to classify cell lineage and subtype.

Cytogenetics and Molecular Studies

  • FISH, PCR for specific translocations (e.g., t(14;18), MYC rearrangements).

Staging – Ann Arbor Staging System (with Cotswolds modification)

  • Stage I: single lymph node region or single extranodal site.

  • Stage II: ≥2 lymph node regions on same side of diaphragm.

  • Stage III: lymph nodes on both sides of diaphragm.

  • Stage IV: disseminated extranodal involvement.

Additional Workup

  • Complete blood count, LDH, ESR, renal/liver function.

  • Imaging: CT, PET-CT.

  • Bone marrow biopsy (for staging).

Treatment

Choice of treatment depends on subtype, stage, grade, patient age, performance status, and comorbidities.

1. Chemotherapy

  • CHOP regimen:

    • Cyclophosphamide: 750 mg/m² IV day 1.

    • Doxorubicin (hydroxydaunorubicin): 50 mg/m² IV day 1.

    • Vincristine: 1.4 mg/m² IV day 1 (max 2 mg).

    • Prednisone: 100 mg orally daily days 1–5.

  • R-CHOP (adds rituximab for CD20+ B-cell NHL):

    • Rituximab: 375 mg/m² IV day 1.

    • Given every 21 days for 6–8 cycles.

2. Immunotherapy

  • Rituximab: anti-CD20 monoclonal antibody, 375 mg/m² IV weekly × 4 or in combination regimens.

  • Obinutuzumab: alternative anti-CD20 for follicular lymphoma, 1000 mg IV day 1, 8, 15 (cycle 1) then day 1 of subsequent cycles.

3. Targeted Therapy

  • Ibrutinib: BTK inhibitor, 560 mg orally daily (mantle cell lymphoma).

  • Acalabrutinib: 100 mg orally twice daily (mantle cell lymphoma).

  • Lenalidomide: 25 mg orally daily on days 1–21 of a 28-day cycle (relapsed/refractory NHL).

4. Radiotherapy

  • Localized disease (stage I/II) or palliation.

5. Stem Cell Transplantation

  • Autologous or allogeneic transplant in relapsed/refractory aggressive NHL.

6. CAR T-cell Therapy

  • Axicabtagene ciloleucel, tisagenlecleucel for relapsed/refractory large B-cell lymphoma.

7. Supportive Care

  • Growth factor support (filgrastim).

  • Infection prophylaxis in immunosuppressed patients.

Follow-Up and Surveillance

  • Every 3–6 months for first 2 years, then every 6–12 months.

  • Monitor for recurrence, treatment-related toxicity, and secondary malignancies.

Prognosis

Prognostic Factors – International Prognostic Index (IPI)

  • Age >60 years.

  • Ann Arbor stage III/IV.

  • Elevated LDH.

  • Poor performance status (ECOG ≥2).

  • 1 extranodal site.

Low-risk (0–1 factors): >80% 5-year survival.
High-risk (4–5 factors): ~26% 5-year survival.






on

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)