Associate professor at the University of Washington School of Medicine and an Associate Member of Fred Hutchinson Cancer Research Center
Please briefly describe Hodgkin lymphoma.
Hodgkin lymphoma (HL) is a common type of lymph node cancer that usually occurs in younger people but can also occur later in life. It has two age peak incidences: one in the mid-20s to mid-30s and the other in the mid-50s to mid-60s. Its cause is currently unknown; there is a hypothesis that HL is related to Epstein-Barr virus, the same virus that causes mononucleosis—but this has not been confirmed.
HL is unique in that tumor cells trigger the inflammation response in the lymph nodes. When a pathologist examines lymph node specimens from a person with HL, they see a lot of inflammatory cells and only 1-2% of actual tumor cells. These tumor cells are called Reed-Sternberg (R-S) cells. R-S cells are considered to trigger the entire process of tumor development. When seen under a microscope, they are typically very large and look abnormal compared to other cells, and are therefore clearly identifiable on a lymph node biopsy. They usually have two nuclei instead of one—a so-called “binucleated” cell. In some cases there are so-called “atypical” R-S cells, but they are always present. The presence of R-S cells is a characteristic feature of HL; they are considered a hallmark of this lymphoma.
HL typically develops initially within one area of lymph nodes. It can then spread to adjacent lymph nodes and eventually to other body organs. Determining the extent to which the disease has spread is called staging. HL is staged using the Ann Arbor Staging System. If a patient has HL in just one nodal area, it is called Stage I. If it is present in several nodal areas on one side of the diaphragm, it is called Stage II. If nodal areas on both sides of the diaphragm are involved, it is called Stage III. If lymphoma is detected in the bone marrow or other inner organs, it is Stage IV disease.
Stages I and II are considered early stage HL, while Stages III and IV are considered advanced stage HL. The stage of HL is important clinically because the management of early stage and advanced stage are different.
We also take into consideration whether or not patients have so-called B symptoms, or constitutional symptoms. These include persistent fevers without an infection or other reasons, drenching night sweats, and weight loss (more than 10% over six months or less). If patients have any of those symptoms, their staging system acquires the designation “b” (eg, Stage Ib, IIb, IIIb, or IVb). If patients do not have those symptoms, the designation is “a” (eg, Stage Ia, IIa, IIIa, or IVa).
There are several subtypes of HL. Three subtypes are grouped together as “classical HL.” The most common, and the best understood, classical HL subtype is nodular sclerosis HL, so-called because it is associated with sclerosis (scarring) in the lymph nodes, which is clearly identifiable by microscopic examination.
Another HL subtype is nodular lymphocyte-predominant HL. This is managed somewhat differently from classical HL subtypes; we believe that it is closely related to indolent non-Hodgkin lymphomas (NHL). Currently we do not have a consensus on the best treatment for this disease, but luckily it is quite indolent; many patients will have a very long lasting disease course over years, sometimes decades, without significantly affecting their quality of life.
How common is HL?
There will be about 9,000 new cases of HL diagnosed in 2012. The incidence of HL has been relatively stable over the past several decades.
How is HL typically treated?
The initial treatment of HL critically depends on the stage of the disease at diagnosis. Patients with early disease stage (Stages I and II) are typically treated with a limited number of chemotherapy cycles, typically three or four, with one cycle being one month in duration and consisting of two treatments twice a month. Some patients will also receive radiation therapy to involved lymph nodes. The role of radiation therapy is debated, but most institutions will add radiation to the disease site for patients with Stage I and Stage II disease. In the United States, Canada, and Europe, a chemotherapy regimen consisting of adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine (referred to as “ABVD”) is very widely used. Patients with advanced staged disease are typically treated with ABVD chemotherapy without radiation, using an increased number of cycles, typically six.
With these treatments, we tend to get quite outstanding results; the vast majority of patients with HL—about 90% of early-stage and up to 70% of late-stage patients—will be cured using these treatment regimens.
A German HL study group recently created a very intense and aggressive chemotherapy regimen called BEACOPP, which consists of bleomycin, etoposide, adriamycin (doxorubicin), cyclophosphamide, oncovin (vincristine), procarbazine, and prednisone. BEACOPP slightly increased the cure rate and remission rate in high-risk HL; however, this regimen was not rapidly adopted in the United States due to its toxicity and due to the very good results seen with ABVD.
Patients whose HL does not respond right away to ABVD treatment are treated with what we call a “salvage” regimen. The salvage regimens typically used are ICE (ifosfamide, carboplatin, and etoposide) or ESHAP (etoposide, methylprednisone, high-dose cytarabine, and cisplatin). Occasionally we also use gemcitabine-based combinations. When patients receive salvage treatment with these therapies, we expect about a 70% response rate; half of these responses will be complete remission. However, relapsed or refractory HL cannot be cured at this point with chemotherapy alone; as a standard in North America and Europe, we recommend an autologous stem cell transplant. About half of those patients who respond to salvage therapy will be cured with an autologous stem cell transplant.
A very small number of patients who relapse after autologous stem cell transplant or have very refractory disease could also consider an allogeneic stem cell transplant, but this is considered on a patient-by-patient basis.
What are the main areas of research for HL?
Since the cure rate for HL is so high, there are two main areas of research.
First, we are looking at whether we can minimize toxicity of treatment and still maintain the same cure rate. There are studies that are trying to remove one of the drugs at a time from the ABVD regimen, to see if the cure rate is the same but the toxicity is lower. We are also trying to figure out whether we can completely omit radiation therapy for early-stage treatment, and just treat patients with three or four cycles of chemotherapy alone.
Second, we are making a big effort to help patients who are not cured with ABVD and/or autologous transplant. This is a very challenging situation; however, we have had a first breakthrough in this area recently, with excellent results from a clinical trial on brentuximab vedotin (Adcetris) that showed remarkable activity in highly refractory HL. This is a significant advance for this disease. Overall we are working to identify novel agents and regimens that help patients when standard chemotherapy and autologous transplant does not work.
Do you talk with your patients about enrolling in a clinical trial?
Yes, absolutely. I work in an academic institution, and our mission is to continue to improve the clinical science of HL and offer patients the best possible treatments; if we have available clinical trials, we offer participation in trials to all patients who come through our institution. There are certainly benefits that patients get from participating in clinical trials; potentially they could receive better therapies that would not be available on a broader basis for five or more years. We are even conducting clinical trials in a newly diagnosed disease setting, despite our expectation that 80% or more patients will be cured with conventional treatment. We still enroll patients in such studies, which have the potential to further increase the cure rate for HL.
How are you involved with the Lymphoma Research Foundation (LRF)?
Would you recommend to a patient that they become involved with LRF?
Yes. LRF is a unique, not-for-profit altruistic organization that has a very important mission. They have several goals that they accomplish under their overall mission of patient advocacy and helping patients and their families. They offer great educational initiatives and connect patients and their families with other patients around the country who have the same type of disease, the same type of treatment, or the same type of challenges. When patients come back to my clinic after connecting with LRF, they feel like they are not alone with their cancer, they have other people they can talk to, and they have a resource they can turn to if they have questions. Physicians do not always have enough time to talk to patients as much as they would like, to explain all aspects of their disease therapy. LRF is a fantastic resource for patients and families to turn to when they want to learn more about their disease, or to hear different perspectives about their disease and treatment, beyond what they hear from just one treating physician.
Is there anything you would like to add?
I would certainly advocate and encourage patients to always seek opinions of at least one academic clinician who is involved in treating HL; there are so many new clinical trials and potential options that sometimes do not infiltrate traditional medical practice quickly, especially for relatively rare cancers. I encourage patients to inquire about new knowledge and new clinical trials when they’re diagnosed with diseases like HL or any other types of cancer.
Updated: June 15, 2012