Hodgkin's Lymphoma

Hodgkin's Lymphoma

• Hodgkin lymphoma is a lymphatic malignancy.
• It is commonly found in cervical lymph nodes.
• The incidence rate of Hodgkin lymphoma is an estimated 2.6 cases per 100,000 people in the United States.
• Hodgkin lymphoma represents 11% of all lymphomas seen in the United States.
• Hodgkin lymphoma is more common in males.
• It presents with a bimodal age distribution, affecting individuals aged 20-40 and those 55+.
• It generally has a good prognosis.

Risk Factors

• Male sex is a risk factor.
• Adolescents and young adults are at higher risk.
• A past history of Epstein-Barr virus infection is a risk factor.
• It is found more commonly in developing countries compared to North America and Western Europe.
• The estimated incubation time is 4.1 years.
• HIV/AIDS is a risk factor; most cases are EBV positive.
• Autoimmune diseases are a risk factor.
• Exposure to pollution is a risk factor.
• Cigarette smoking is a risk factor.
• Having a family history increases the risk.

Clinical Presentation

• Often presents as painless supra-diaphragmatic lymphadenopathy, enlarging over months.
• Common sites include mediastinal involvement, left neck nodal enlargement, or right neck nodal enlargement in about 60% of patients.
• Other sites include splenic, axillary, abdominal, hilar, or inguino-femoral areas.
• B symptoms occur in ~30% of cases.
  • This includes weight loss.
  • Fever is also a common symptom
  • And drenching night sweats
• More common in stage 3/4, mixed cellularity, and lymphocyte-depleted HL.
• Pain in lymph nodes may occur with alcohol consumption (paraneoplastic symptom).
• chronic pruritus may be presenting factor
• A large mediastinal mass can cause chest pain and shortness of breath.

Staging

• Stage I: Involvement of a single lymph node or group of adjacent nodes.
• Stage II: Involvement of two or more groups of lymph nodes on the same side of the diaphragm.
• Stage III: Involvement of lymph nodes on both sides of the diaphragm, or involvement of lymph nodes above the diaphragm plus spleen involvement.
• Stage IV: Widespread disease in lymph nodes, bone marrow, and organs like the liver or lungs.
• Stage letters:
  • A: Patients have not experienced significant weight loss (more than 10 percent in six months), drenching night sweats, or fevers.
  • B: Patients have lost weight (more than 10 percent in six months) and have experienced drenching night sweats or fevers.
  • X: Lymphoma is greater than 10 cm (4 inches) wide, also called bulky disease.

Histology/Subtypes

• Characterized by scattered large mononuclear Hodgkin and multinucleated Reed-Sternberg cells.
• Neoplastic cells are surrounded by T lymphocytes.
• Hodgkin's is classified into classical HL/cHL and nodular lymphocyte-predominant HL/NLP-HL.
• Classical HL accounts for 95% of HL and is further divided into 4 subtypes:

Nodular sclerosis (70%)

• It is the most common type.
• Common in younger patients
• Presents with early-stage disease.
• Most present with stage II disease (2/3 have either stage I or II disease).
• B symptoms occur in 40% of cases.

Mixed cellularity (25%)

• Second most common subtype of classic Hodgkin lymphoma.
• Accounts for 20-25% of classic Hodgkin lymphoma.
• Bimodal incidence: pediatric population and elderly patients
• EBV infection in 75% of cases.
• More common in patients with immunodeficiency, HIV.
• It presents in: Lymph nodes (70%) > spleen (30%) > bone marrow (10%) > liver (3%) > other organs (1 - 3%).
• Rarely limited to a single region and is more likely to involve extralymphatic tissues compared to other subtypes.
• Mediastinal involvement is rare.
• B symptoms are common.
• May be diagnosed in all clinical stages, more commonly with stage II and III disease.

Lymphocytic rich (5%)

• Patients tend to have peripheral adenopathy without bulky mediastinal involvement.
• Usually presents with early stage disease.
• Treatment outcomes are excellent using modern combination chemotherapy regimens with rare treatment failures.

Lymphocytic depleted (<1%)

• Lymphocyte depletion HL presents with extensive extranodal disease.
• Affects elderly patients.
• Associated with AIDS infection.
• Patients with LDCHL and MCCHL have a significantly worse prognosis compared to patients with NSCHL.
• Those with LRCHL have the best prognosis.

NLP-HL

• Presents in males with localized painless peripheral lymphadenopathy in the neck that often spares the mediastinum.
• Shows a more indolent course with a tendency for late relapses.

Conventional Treatment

• Radiation therapy is involved-site radiation therapy/ISRT.
  • In early-stage disease, no B symptoms, not bulky disease, and ESR < 50.
  • It may be given with or without ABVD.
• Radiosensitizers/Radioprotectors
  • Glutamine: 30g total (10 g tid), prevents mucositis, tissue protective.
  • Homeopathic X-ray & Radium
  • Berberine, Niacinamide, Nigella Sativa, Quercetin

Chemotherapy

• In early-stage disease, ABVD is used with or without radiation therapy.

ABVD

• Adriamycin/Doxorubicin
  • Drug Classification: anthracycline antineoplastic antibiotic.
  • Mechanism of Action:
    • Doxorubicin binds directly to DNA via intercalation between base pairs on the DNA helix.
    • Doxorubicin also inhibits DNA repair.
    • Actions result in the blockade of DNA and RNA synthesis and fragmentation of DNA.
    • Side effect is cardiotoxicity which can be decreased by using
      • CoQ10 400-600mg
      • Hawthorne
      • Fish oil 2-3g
      • Vitamin C which attenuates cardiotoxicity of doxorubicin
      • Grapeseed extract OPC
      • Rhodiola
• Overall Reduction in Toxicity
  • selenium
  • melatonin
  • grapeseed OPCs
  • fish oil
  • EGCG
• Improve efficacy
  • Vitamin C
  • EGCG
  • Quercetin- helps drug accumulate in cancer cells
• Contraindicated
  • Contraindicated with NAC/Glutathione ~ increase drug resistance

Bleomycin

• Drug Classification: anti-tumor antibiotic.
• Mechanism of action: causes DNA strand scission through formation of metal complex, inhibiting DNA synthesis.
• Side effects include pneumonitis and can cause severe lung damage/fibrosis.
  • Mechanisms behind pulmonary fibrosis
    • BLM causes oxidative stress, increases production of pro-inflammatory cytokines, and activates fibroblasts, causing damage to pulmonary structures, ending in pulmonary fibrosis.
    • NFkb promotes the expression of tissue inhibitor of metalloproteinase 1 (TIMP1) and osteopontin (OPN).
• Current therapy for bleomycin-induced lung damage is inadequate.Integrative support

Supplements

• Chamomile
• Fuzheng Huayu (FZHY) formula
• Astragalus polysaccharide attenuates bleomycin-induced pulmonary fibrosis by inhibiting TLR4/ NF-κB signaling_pathway
• Ginsenoside:Role of nuclear factor-kappa B
  • anti-fibrotic, anti-inflammatory anti-tumor effects
• Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-KB/NLRP3-mediated
• Resveratrol alleviates bleomycin-induced pulmonary fibrosis
• Glutamine restores mitochondrial respiration in bleomycin-injured epithelial cells
• Quercetin

Vinblastine

• Drug Classification: mitotic inhibitor.
• Mechanism of action: Inhibits microtubule formation and division.
• Prevents polymerization/depolymerization.
• May also interfere with nucleic acid and protein synthesis by blocking glutamic acid utilization.
• Side Effects:
  • Leukopenia, fatigue, constipation, N/V
  • Neuropathy
    • L-carnitine
    • B6
    • ALA
    • glutamine
    • magnesium
  • Tumor lysis syndrome
• Synergist: Quercetin, Celecoxib
• Contraindications/cautions: Curcumin, CYP3A4 metabolism
• pretreatment curcumin may reduce effectiveness
• CYP3A4 metabolism- caution with botanicals with CYP3A4 metabolism

Dacarbazine

• Drug Classification: alkylating agent
• Mechanism of Action:
  • Structural analog of purine precursor
  • Forms ions that bind to DNA
• Side effects: leukopenia, thrombocytopenia
  • N/V- Occurs in 90% of patients, use Ginger, peppermint, acupuncture, small frequent meals to minimize this.
  • Anorexia
  • Hepatotoxicity: use Silymarin mitigate damage through pretreatment.

Other treatment options

• OR CHOP/CHOP-R ( rituximab CD20+)
  • cyclophosphamide
  • doxorubicin
  • vincristine
  • prednisone