13-33: Hodgkin Lymphoma

Hodgkin lymphoma is characterized by lymph node biopsy showing Reed-Sternberg cells in an appropriate reactive cellular background (eFigure 13–34). The malignant cell is derived from B lymphocytes of germinal center origin.

There is a bimodal age distribution, with one peak in the 20s and a second over age 50 years. Most patients seek medical attention because of a painless mass, commonly in the neck. Others may seek medical attention because of constitutional symptoms such as fever, weight loss, or drenching night sweats, or because of generalized pruritus. An unusual symptom of Hodgkin lymphoma is pain in an involved lymph node following alcohol ingestion.

An important feature of Hodgkin lymphoma is its tendency to arise within single lymph node areas and spread in an orderly fashion to contiguous areas of lymph nodes. Late in the course of the disease, vascular invasion leads to widespread hematogenous dissemination.

Hodgkin lymphoma is divided into two subtypes: classic Hodgkin (nodular sclerosis, mixed cellularity, lymphocyte rich, and lymphocyte depleted) and non-classic Hodgkin (nodular lymphocyte predominant). Hodgkin lymphoma should be distinguished pathologically from other malignant lymphomas and may occasionally be confused with reactive lymph nodes seen in infectious mononucleosis, cat-scratch disease, or drug reactions (eg, phenytoin).

Patients undergo a staging evaluation to determine the extent of disease, including serum chemistries, whole-body PET/CT scan, and bone marrow biopsy. The staging nomenclature (Ann Arbor) is as follows: stage I, one lymph node region involved; stage II, involvement of two or more lymph node regions on one side of the diaphragm; stage III, lymph node regions involved on both sides of the diaphragm; and stage IV, disseminated disease with extranodal involvement. Disease staging is further categorized as "A" if patients lack constitutional symptoms or as "B" if patients have 10% weight loss over 6 months, fever, or drenching night sweats (or some combination thereof).

Chemotherapy is the mainstay of treatment for Hodgkin lymphoma and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) remains the standard first-line regimen. Even though other regimens such as escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) may improve response rates and reduce the need for consolidative radiotherapy, they are usually associated with increased toxicity and lack a definitive overall survival advantage. Low-risk patients are those with stage I or II disease without bulky lymphadenopathy or evidence of systemic inflammation. They traditionally receive a combination of short-course chemotherapy with INRT, but INRT can be eliminated for those with an early negative PET/CT scan without a significant change in outcomes (see Table 39–3). High-risk patients are those with stage III or IV disease or with stage II disease and a large mediastinal or other bulky mass or systemic inflammation. These patients are treated with a full course of ABVD for six cycles. Pulmonary toxicity can unfortunately occur following either chemotherapy (bleomycin) or radiation and should be treated aggressively in these patients, since it can lead to permanent fibrosis and death. A negative interim PET/CT scan after two cycles of chemotherapy can be used to identify patients with an excellent progression-free survival who can have bleomycin eliminated from their treatment. Conversely, an abnormal interim PET/CT scan is associated with a worse prognosis and should prompt early intensification of treatment to achieve a complete response (CR).

Classic Hodgkin lymphoma relapsing after initial treatment is treatable with high-dose chemotherapy and autologous hematopoietic stem cell transplantation. This offers a 35–50% chance of cure when disease is still chemotherapy responsive. The antibody-drug conjugate brentuximab vedotin has shown impressive activity in patients relapsing after autologous stem cell transplantation (overall response rate [ORR] of 75%; CR of 34%) and is FDA-approved for this indication. Last, immune checkpoint inhibition by PD1 blockade with nivolumab or pembrolizumab has shown remarkable activity (ORR of 65%) and is another option for patients with relapsed or refractory disease.

All patients should be treated with curative intent. Prognosis in advanced stage Hodgkin lymphoma is influenced by seven features: stage, age, gender, hemoglobin, albumin, white blood cell count, and lymphocyte count. The cure rate is 75% if zero to two risk features are present and 55% when three or more risk features are present. The prognosis of patients with stage IA or IIA disease is excellent, with 10-year survival rates in excess of 90%. Patients with advanced disease (stage III or IV) have 10-year survival rates of 50–60%. Inferior results are seen in patients who are older, those who have bulky disease, and those with lymphocyte depletion or mixed cellularity on histologic examination. Non-classic Hodgkin lymphoma (nodular lymphocyte predominant) is highly curable with radiotherapy alone for early-stage disease; however, for high-stage disease, it is characterized by long survival with repetitive relapses after chemotherapy or monoclonal anti-CD20 antibody therapy.

• All patients should be sent to an oncologist or hematologist.

• Secondary referral to a radiation oncologist might be appropriate.

Patients should be admitted for complications of the disease or its treatment.