Hodgkin Lymphoma
Summary of Key Points
Incidence
• Estimated 9060 new cases in United States in 2012 with 1190 deaths
• U.S. age-adjusted incidence rate of 2.8 per 100,000 per year
• Higher incidence among males than females
• Highest incidence in North America and Western Europe
• Bimodal age distribution (peaks at 15 to 35 years and then again later in life)
Biological Characteristics
• Hodgkin Reed-Sternberg and lymphocyte-predominant (LP) cells derive from germinal center B cells. Hodgkin Reed-Sternberg and LP cells are rare in the lymphoma tissue, and interactions with other cells in the microenvironment may play a role in the pathophysiology of the disease.
• In classic Hodgkin lymphoma (HL), Hodgkin Reed-Sternberg cells express CD30 and have lost expression of B-cell markers.
• Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) represents a distinct clinicopathological entity characterized by scattered large “popcorn” cells that express CD45 and CD20.
• Epstein-Barr virus may be involved in the pathogenesis of some classic HL cases, particularly in tropical areas.
Staging Evaluation
• Physical examination with attention to peripheral nodes and spleen
• History including presence or absence of pruritus, drenching night sweats, fevers, and significant weight loss
• Laboratory evaluation to include complete blood cell count with differential, albumin, and erythrocyte sedimentation rate
• Positron emission tomography/computed tomography (PET/CT)
• Bone marrow biopsy not indicated in early-stage disease and may no longer be needed in advanced-stage disease in patients undergoing PET
Primary Therapy
• Early-stage non-bulky classic HL
ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy (two to four cycles) with 20 to 30 Gy of involved-field radiation therapy (IFRT) with number of cycles and dose of radiation dictated by high-risk features
Interim PET likely to select patients who benefit most from radiation therapy
1. All of the following are adverse prognostic indicators for patients with Hodgkin lymphoma (HL) EXCEPT:
2. True or False: Hodgkin Reed-Sternberg cells are CD30+, whereas nodular lymphocyte-predominant cells are CD30−.
3. A 25-year-old woman has stage II HL with a large mediastinal mass (≥1/3 mediastinal mass ratio) and B symptoms. All laboratory test results are normal. What is the estimated 5-year freedom from progression (FFP) for this patient based on the International Prognostic Score (IPS)?
4. Which type of HL is most frequently associated with EBV positivity in North America and Europe?
A Lymphocyte-predominant classic HL
B Nodular lymphocyte-predominant HL
5. Which of the following is the most appropriate treatment for a patient with advanced-stage HL and an IPS of 4?
B ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)
C Multiagent chemotherapy + high-dose chemotherapy consolidation and autologous hematopoietic stem cell transplant
D R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone)
6. What is the single agent response rate to brentuximab vedotin in relapsed HL?
1. Answer: C. Epstein-Barr positivity is not an independent prognostic factor for HL. Age 45 years or older, male gender, hemoglobin value less than 10.5 g/dL, and increased erythrocyte sedimentation rate have all been shown to be negative prognostic factors. Additionally, bulky disease, albumin value less than 4 g/dL, stage IV disease, leukocytosis (≥15,000/µL white blood cells), and lymphopenia (<600 lymphocytes/µL or <8% total white blood cell count) are poor prognostic factors.
2. Answer: TRUE. Hodgkin Reed-Sternberg cells are CD30+, which is important in the treatment of relapsed disease. Brentuximab vedotin, an antibody-drug conjugate, uses an anti-CD30 antibody conjugated to an anti-tubule agent to target these cells and cause cell cycle arrest and apoptosis. This drug is approved for the treatment of relapsed disease. Nodular lymphocyte-predominant HL cells are CD45+ and CD20+ in all cases and usually CD30−.
3. Answer: D. The IPS for HL identifies age 45 years or older, male gender, hemoglobin value less than 10.5 g/dL, albumin value less than 4 g/dL, stage IV disease, leukocytosis (≥15,000 white blood cells/µL), and lymphopenia (<600 lymphocytes/µL or <8% total white blood cell count) as adverse prognostic factors. Patients with 0 risk factors have a 5-year FFP of 84%.
4. Answer: D. In North America and Europe, mixed-cellularity classic HL is most commonly associated with EBV. In tropical areas, nearly all classic HL is EBV+.
5. Answer: B. Patients with advanced HL should receive either ABVD or escalated BEACOPP chemotherapy. Stanford V is an inferior therapy in high-risk patients. Consolidation with high-dose chemotherapy and autologous stem cell transplantation in first remission does not confer improved progression-free or overall survival rates. R-CHOP chemotherapy is used in the treatment of non-Hodgkin lymphomas.
6. Answer: A. Brentuximab vedotin is well tolerated and resulted in an overall response rate of 75% (complete response rate of 34%) in 102 patients with relapsed or refractory HL after autologous stem cell transplant. This agent is now FDA-approved for use in HL patients after two prior regimens.
