Hodgkin Lymphoma (HL)

SOURCE

Source: Chan A, Sessions J. Lymphomas. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=133894009. Accessed April 13, 2017.

DEFINITION

• Clonal malignant lymphoid disease of transformed lymphocytes.

  • Malignant cell known as Reed–Steinberg cell.

ETIOLOGY

• Unknown.

  • Laboratory evidence supports infectious exposure as potential cause.

    • Increased risk with Epstein–Barr virus (EBV)

  • Genetic factors.

PATHOPHYSIOLOGY

• B-cell transcriptional processes disrupted.

  • Prevents expression of B-cell surface markers and production of immunoglobulin messenger RNA (mRNA).

  • Alterations in normal apoptotic pathways favor cell survival and proliferation.

• Malignant Reed–Sternberg cells overexpress nuclear factor-κ B.

  • Associated with cell proliferation and anti-apoptotic signals.

  • Upregulated by infections with viral and bacterial pathogens.

    • Epstein–Barr virus found in many, but not all, Hodgkin lymphoma (HL) tumors.

EPIDEMIOLOGY

• HL represents <1% of all known cancers in United States.

• Bimodal distribution with first peak in third decade and small peak occurring after age 50

RISK FACTORS

• EBV

• HIV

CLINICAL PRESENTATION

• Most patients with HL present with painless, rubbery, enlarged lymph node in supradiaphragmatic area and commonly have mediastinal nodal involvement.

SIGNS AND SYMPTOMS

• Constitutional (B symptoms) in ~25% of all patients.

  • Fever.

  • Drenching night sweats.

  • Weight loss.

DIAGNOSIS

MEANS OF CONFIRMATION AND DIAGNOSIS

• Requires presence of Reed–Sternberg cells in lymph node biopsy.

LABORATORY TESTS

• Metabolic panel.

• Complete blood count (CBC)

• Erythrocyte sedimentation rate (ESR)

IMAGING

• Chest radiography.

• Computed tomography (CT) of chest, abdomen, and pelvis.

• Positive emission tomography (PET)

• Integrated PET-CT

DIAGNOSTIC PROCEDURES

• Excisional lymph node biopsy.

• Laparoscopy or laparotomy of strategic sites.

• Bone marrow aspiration and biopsy with advanced-stage disease.

STAGING

• Based on clinical or pathologic findings.

  • Localized disease (stages I, II, and IIE) in ~50% of patients.

  • Advanced disease (stage III or IV) in other half.

    • 10–15% have metastatic disease (stage IV)

DIFFERENTIAL DIAGNOSIS

• Non-Hodgkin lymphoma

• Infectious mononucleosis.

• Metastatic cancer.

DESIRED OUTCOMES

• Maximize curability while minimizing short- and long-term treatment-related complications.

TREATMENT: GENERAL APPROACH

• Combination chemotherapy is primary treatment modality.

TREATMENT: NONPHARMACOLOGIC THERAPY

• Therapeutic role of surgery limited, regardless of stage.

• Radiation therapy (RT)

  • Early-stage HL treated with combination chemotherapy and RT

  • Advanced-stage HL treated with combination chemotherapy with or without RT

TREATMENT: PHARMACOLOGIC THERAPY

• Initial chemotherapy.

  • Two to eight cycles of chemotherapy ...