As noted previously, Hodgkin’s disease is a group of disorders with a characteristic clinical course. The early studies by Henry Kaplan defined the typical pattern of spread of Hodgkin’s disease. As opposed to the non-Hodgkin’s lymphomas, Hodgkin’s disease tends to spread to contiguous lymph node groups. Thus, intricate staging at the time of diagnosis is critical for developing a plan of treatment. The incidence of Hodgkin’s disease demonstrates a bimodal age-specific pattern. There is an early peak between the ages of 20 and 30. Some have suggested that there is an infectious etiology for this form of Hodgkin’s disease as there is increasing risk for Hodgkin’s disease with higher socioeconomic status. The later peak, occurring about age 50, is not related to socioeconomic status. There are many reasons to think that the etiology of the early peak of Hodgkin’s diseases is different from the etiology of the cases that occur in elderly individuals.
Classification and Clinical Presentation
All forms of Hodgkin’s disease have demonstrable Reed-Sternberg cells, which are large binucleated cells with prominent nucleoli, and although not pathognomic for Hodgkin’s disease these are typical. The debate regarding the origin of this cell continues. There are four subtypes of Hodgkin’s disease. In decreasing frequency, they are nodular sclerosing, mixed cellularity, lymphocyte predominant, and lymphocyte depleted.
Most patients present with an enlarged lymph node; however, there is some difference in the clinical presentation from older to younger patients. Older patients are more likely to have systemic symptoms and abdominal disease, especially bulky abdominal disease. The most common histologic pattern in all age groups is nodular sclerosing, but it appears from a multitude of studies that with advancing age there is decreasing nodular sclerosis and increasing mixed cellularity.
The clinical presentation of Hodgkin’s disease as noted is typically with adenopathy, with more than 70% of people presenting with palpable lymph node enlargement. Rarely, the lymph nodes become painful after consumption of alcoholic beverages. As many as a third of patients will develop so-called B symptoms with fevers, night sweats, and weight loss of more than 10% of body weight. Other symptoms such as fatigue, weakness, and pruritus occur commonly but are not officially considered B symptoms. Presence of true B symptoms has adverse prognostic implications.
- Acute Leukemias
- Myeloproliferative Disorders
An important point to differentiate between the Hodgkin’s lymphomas and the non-Hodgkin’s lymphomas is the relative importance of histologic classification and staging. The treatment plan for Hodgkin’s disease is critically dependent on accurate staging, whereas the histologic subtype is less important. Conversely, in the non-Hodgkin’s lymphomas, the histologic subtype is the critically important determinant of therapy, and, while staging is important, it is not as critically important as in Hodgkin’s disease.
The Ann Arbor classification is the most commonly used staging system for Hodgkin’s disease (
Table 38.4). The suffix E represents the presence of extralymphatic involvement with disease, and the suffix A or B denotes presence or absence of B symptoms, as noted in the previous section.
The optimal staging procedures for Hodgkin’s disease continue to be an area of debate. Given that therapy is dependent on stage, accurate staging is essential. CT scans of the chest, abdomen, and pelvis can accurately search for enlarged lymph nodes. Bone marrow biopsy should also be obtained. Routine laboratory studies, including liver and renal function, uric acid level, and the erythrocyte sedimentation rate (ESR), are useful. Specialized staging studies for patients with otherwise localized disease are important. A lymphangiogram to evaluate periaortic and iliac abnormalities is better than CT scans at detecting normal-size lymph nodes that are involved with Hodgkin’s disease. Staging laparotomy and splenectomy at one time were a standard intervention for all patients with stage I, II, or III Hodgkin’s disease. However, this continues to be evaluated, and clearly those patients who will be receiving chemotherapy for other indications should be spared laparotomy and splenectomy. Gallium scan is useful both at the initial diagnosis and in follow-up of patients. It is recommended that it be obtained before initiating therapy to determine if the lymphoma is gallium uptake positive because treatment with chemotherapy can produce false-negative results in the gallium scan.
Hodgkin’s disease is a curable malignancy, and treatment should be initiated with curative intent. Both radiotherapy and combination chemotherapy can cure Hodgkin’s disease. The choice of therapy modality is dependent on the stage of disease. Localized disease (stage IA, IIA, IB, and IIB) is typically treated with radiotherapy. Abbreviated courses of chemotherapy before radiation treatment may improve outcome in early-stage Hodgkin’s disease.
The principles of radiation treatment were established by Henry Kaplan. Although doses less than 4000 centigray (cGy) were effective in inducing responses, 4000 centigray was required for curative therapy. Because of the typical contiguous pattern of spread of Hodgkin’s disease, radiation treatment ports could be devised to cover all known involved regions of disease plus one additional nodal group. Using current radiotherapy, patients with localized disease (stage IA and IIA) have a cure rate greater than 80%. B symptoms reduce the cure rate to approximately 70%.
More advanced disease requires combination chemotherapy. DeVita developed the regime MOPP [nitrogen mustard, Oncovin (vincristine), procarbazine, and prednisone] and for the first time demonstrated long-term disease-free survival for patients with advanced-stage Hodgkin’s disease. Over the past 20 years, attempts at refining MOPP therapy have concentrated on improving the response rates, as well as limiting toxicity. Most recently, ABVD (adriamycin, bleomycin, velban, and dexamethasone) has been shown to be more effective than MOPP, with less toxicity. Hybrid regimens combining MOPP and ABVD are also an improvement over MOPP alone. Toxicity from chemotherapy includes acute side effects such as bone marrow suppression and a high incidence of sterility. Secondary malignancies, including leukemia and solid tumors, have been recognized as a late toxicity from these therapies.
Using both chemotherapy and radiotherapy together has been referred to as combined modality therapy. The rationale for combined modality therapy in advanced-stage Hodgkin’s disease rests with documentation that recurrence frequently occurs in the site of previous bulk adenopathy. Thus, in retrospective studies, radiotherapy to areas of previous bulk disease once chemotherapy has been completed has been associated with improved survival rates. Nonetheless, no randomized trial has demonstrated superior results with combined modality therapy. There is concern regarding increased toxicity when combining chemotherapy and radiotherapy. Despite the controversy, patients with bulky mediastinal adenopathy are routinely treated with combined modality therapy because they fare less well with single modality therapy. As mentioned earlier, there is support for combined treatment for early-stage disease as well.
Patients who relapse with Hodgkin’s disease need to be accurately restaged. The prognosis for those who never achieved a CR or relapse within 12 months of obtaining a CR is significantly worse than for those who remain in complete remission for a significant duration of time. Patients who relapse after curative radiotherapy should be treated with chemotherapy and have a high likelihood of response and long-term disease-free survival. Patients who relapse with localized disease after chemotherapy can be treated with salvage radiotherapy. For those patients relapsing in less than 12 months, a salvage regimen that is noncross-resistant with their induction regimen should be considered. High-dose therapy with autologous or allogenic bone marrow support can also be considered for younger patients. There is little evidence that older patients can undergo these aggressive regimens.
Prognosis and Survival
Many studies have evaluated the prognostic factors associated with surviving Hodgkin’s disease. Increasing age is a poor prognostic factor. Different investigators have used different age cutoffs, but typically survival worsens for patients over the age of about 40 to 50. In the recent study reported by Canellos et al., 5-year survival for patients under the age of 40 was 80%; for those 40 to 60, it was was 63%; and for those over 60 survival was 31%.
It has been suggested that the inability to tolerate chemotherapy has been a factor in the poor prognosis for elderly patients. Although this may be true, other factors may also play a role in the worse outcome for elderly patients. Given the different epidemiologic phenomena and the response to therapy for this age group, patients over the age of 60 with Hodgkin’s disease probably have a different disease from younger patients. Other prognostic factors, including bulky disease, high LDH, and extranodal site involvement, may be as important as age.
Revision date: June 22, 2011
Last revised: by Janet A. Staessen, MD, PhD