HODGKIN DISEASE

HODGKIN DISEASE - Mark Steenbergen, DO
BASICS
DESCRIPTION
• A malignant disease of lymphoid tissue, probably caused by clonal proliferation of transformed B cells in the majority of cases, or rarely may involve T cells.
• Reed-Sternberg (RS) cells are pathognomonic.
• Disease spreads to contiguous lymphoid tissue and eventually to nonlymphoid tissue.
• Rye classification-based on pathologic findings
- Lymphocyte predominant: 2-10%
- Mixed cellularity: 20-40%
- Lymphocyte depleted: 2-15%
- Nodular sclerosis: 40-80%
• System(s) Affected: Hemic/Lymphatic/Immunologic
• Synonym(s): Malignant lymphoma
ALERT
Geriatric Considerations
Usually presents in more advanced stage and shows unfavorable histology
Pediatric Considerations
• Increased risk for males
• Young females (>20) who are treated with thoracic radiation are at high risk for breast cancer.
Pregnancy Considerations
• Pregnancy is not known to affect course of disease.
• Not known to affect pregnancy or fetus if therapy can be postponed until delivery.
• Normal pregnancy can occur after treatment, if fertility is maintained.
• Risk of disease progression during pregnancy is variable; management must be individualized.
GENERAL PREVENTION
• Pneumococcal vaccine, if splenectomy is planned for staging.
• Consider vaccines for Haemophilus and Neisseria species as well.
EPIDEMIOLOGY
Predominant sex: Male > Female (1.4:1)
Incidence
• 3.1/100,000
• ~7,000 new cases expected yearly
• Incidence is lower in underdeveloped countries.
Prevalence
• Bimodal age distribution
- Early peak in mid to late 20s
- Later peak around 60-70
• Rare under age 5
RISK FACTORS
• Immunodeficiency (inherited or acquired)
• Autoimmune disorders
• HIV infection
Genetics
• 1st degree relatives: 3 times risk
• Siblings of younger patients: 7 times risk
ETIOLOGY
• Unknown
• EB virus may play a role.
ASSOCIATED CONDITIONS
• T lymphocyte defects, which persist after successful treatment
• Patients with HIV tend to present with more advanced disease.


DIAGNOSIS
SIGNS AND SYMPTOMS
• Asymptomatic lymphadenopathy (usually cervical or supraclavicular)
• Fever (Pel-Epstein pattern)
• Night sweats
• Weight loss
• Fatigue
• Anorexia
• Alcohol-induced pain
• Unexplained itching
TESTS
Lab
• CBC
• Chemistry profile
• ESR
• Liver function tests
• Renal function tests
• HIV (if risk factors present)
• Hepatitis serology (if risk factors present)
• Drugs that may alter lab results: Phenytoin may produce pseudolymphoma.
Imaging
• Chest radiograph
• Thoracic CT scan
• Abdominal and pelvic CT scan (or possibly MR scan)
• PET scan (exact role is under investigation)
• Lymphangiography
• Bone scan, gallium scan, abdominal ultrasound (used infrequently)
Diagnostic Procedures/Surgery
• Excisional lymph node biopsy (needle biopsy not sufficient)
• Exploratory laparotomy with splenectomy; this procedure is becoming uncommon
• Bone marrow biopsy, especially with systemic symptoms
• Liver biopsy (in selected cases)
Pathological Findings
• RS cell
- Abundant cytoplasm
- 2 or more nuclei or nuclear lobes, each with a prominent nucleoli
• Background infiltrate of lymphocytes, histiocytes, granulocytes, plasma cells, and fibroblasts
DIFFERENTIAL DIAGNOSIS
• Non-Hodgkin lymphoma
• Infectious lymphadenopathy
• Other solid tumor metastases
• Sarcoidosis
• Autoimmune disease
• AIDS/HIV infection
• Drug reaction
TREATMENT
• Initial staging is critical to therapy.
• Cotswold classification
- Stage I: Single lymph node group
- Stage II: 2 or more node groups on same side of diaphragm
- Stage III: Node groups on both sides of diaphragm
- Stage IV: Dissemination involving extranodal organs (not the spleen, which is considered lymphoid tissue)
- Subclass designations: A = no symptoms; B = systemic symptoms (fever, night sweats, weight loss >10% body weight); X = bulky disease (widened mediastinum, >1/3 intrathoracic diameter, or >10 cm nodal mass); E = single extranodal site involvement in proximity with known nodal site
GENERAL MEASURES
• Treatment is aimed for cure with minimum toxicity, including treatment-induced late mortality.
• Treatment can be radiation therapy (RT), chemotherapy, or combined radiation and chemotherapy (CMT), based on stage and tumor burden.
- Early stages (favorable prognosis): Low amount (2-3 cycles) chemotherapy plus involved field RT or extended field RT
- Early stages (unfavorable prognosis): Moderate chemotherapy (4 cycles) plus RT
- Advanced stages: Extensive chemotherapy (8 cycles) with or without RT
• Autologous bone marrow transplant for selected patients who fail conventional therapy
Activity
As tolerated
MEDICATION (DRUGS)
First Line
ABVD chemotherapy, 4-week cycles
• Doxorubicin (Adriamycin): 25 mg/m2 IV days 1 and 15
• Bleomycin: 10 mg/m2 IV days 1 and 15
• Vinblastine: 6.0 mg/m2 IV days 1 and 15
• Dacarbazine: 375 mg/m2 IV days 1 and 15
ALERT
• Must be monitored by experienced oncologist
• Contraindications: As in general for chemotherapy
• Precautions: Chemotherapy toxicity, bone marrow suppression
• Significant possible interactions: Refer to the manufacturer's literature.
Second Line
• MOPP chemotherapy, 4-week cycles
- Mechlorethamine (nitrogen mustard): 6 mg/m2 IV days 1 and 8
- Vincristine (Oncovin): 1.4 mg/m2 IV days 1 and 8
- Procarbazine: 100 mg/m2 PO days 1-14 (avoid vanilla, cheese, and wine)
- Prednisone: 40 mg/m2 PO days 1-14 during cycles 1 and 4
• Alternate cycles with MOPP/ABVD to minimize toxicity
• BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)
• Stanford V regimen (nitrogen mustard, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, prednisone)
FOLLOW-UP
PROGNOSIS
• Overall 5-year survival: 83%
• Long-term survival: 75%
• 10-year survival rates correlate with stage at diagnosis
- Stage IA, IB, IIA non-bulky: 85-95%
- Stage IIA bulky: IIB 80-85%
- Stage IIIA: 75-90%
- Stage IIIB: 60-65%
- Stage IV: 55-60%
• Unfavorable prognostic factors in advanced disease
- Sed rate >70
- Age >45
- Male gender
- Albumin 4 g/dL
- Hemoglobin 10.5 g/dL
- Lymphopenia 600 cells/L
- Leukocyte count 15,000 cells/L
COMPLICATIONS
• Secondary malignancies following therapy
• Sterility, gonadal dysfunction
• Hypothyroidism
• Bone marrow suppression
• Immunosuppressed infections, including herpes zoster
• Anemia
• ITP, TTP
• Coronary artery disease, cardiomyopathy
• Radiation pneumonitis, pulmonary fibrosis
• Transient radiation myelopathy (Lhermitte sign)
PATIENT MONITORING
• CBC, nutrition, and hydration during therapy
• Posttreatment monitoring (at least yearly)
- CBC, ESR
- TSH, if RT to the neck
- Chest radiograph
REFERENCES
1. Fung HC, Nademanee AP. Approach to Hodgkin's lymphoma in the new millennium. Hematol Oncol. 2002;20:1-15.
2. Horwitz SM, Horning SJ. Advances in the treatment of Hodgkin's lymphoma. Curr Opin Hematol. 2000;7(4):235-240.
3. Tesch H, Sieber M, Diehl V. Treatment of advanced stage Hodgkin's disease. Oncology. 2001;60(2):101-109.
4. National Comprehensive Cancer Network. NCCN practice guidelines for Hodgkin's disease. Oncology (Huntingt). 1999;13:78-110.
5. Urba WJ, Longo DL. Hodgkin's disease. New Engl J Med. 1992;326:678-687.