Associate Professor of Medicine and Director of the Lymphoma Program at The University of Chicago Medicine, Chicago, Illinois
Can you describe anaplastic large cell lymphoma?
Anaplastic large cell lymphoma (ALCL) is a type of T-cell non-Hodgkin lymphoma. Importantly, non-Hodgkin lymphoma is an umbrella term that includes about 60 different subtypes. About 75 to 85 percent of these subtypes are B-cell lymphomas, and the rest are T-cell lymphomas. In general, T-cell lymphomas are much less common and often harder to treat. The most common T-cell lymphomas in The United States are peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, and ALCL.
An interesting aspect of ALCL is that it is divided into two different types based on a biologic marker called anaplastic lymphoma kinase (ALK). ALK is an abnormal form of a protein on the surface of some cells, due to a chromosomal abnormality called a translocation of chromosomes 2 and 5—written as t(2;5). Patients with this translocation have lymphoma cells that express ALK protein (ALK-positive ALCL) and those without this translocation have lymphoma cells that do not express ALK protein (ALK-negative ALCL). Patients with ALK-positive ALCL tend to be younger and male, with an average age in their 20s, and often have a more optimistic outlook than when the ALK protein is absent. In general, ALK-negative ALCL affects people who are at least in their 40s, and the lymphoma tends to be more resistant to chemotherapy.
One of the most important aspects for ALCL, and any T-cell lymphoma, is to ensure there is an adequate biopsy to prove the diagnosis. These are rare lymphomas that can sometimes be hard to diagnose. They often require a secondary review from a hematopathologist who specializes in lymphoma.
Once the patient is diagnosed, a staging evaluation, which includes a positron emission tomography/computed tomography scan and a bone marrow biopsy, is often done to find out the extent of the disease.
Once doctors have this information, the treatment for ALCL is usually combination chemotherapy and often with consideration of an autologous stem cell transplant to consolidate the results achieved with chemotherapy. In regards to chemotherapy, the most common treatment is CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Some data from Germany suggest that adding etoposide to CHOP (CHOEP) improves outcomes in patients with ALCL under the age of 60.
Once a patient reaches remission, at what point do you consider them to be entering the survivorship phase?
With T-cell lymphoma, survivorship is a tricky issue because these lymphomas are a little more aggressive. ALCL, like other T-cell lymphomas, is not always easy to cure. Even when a patient does enter remission, there is still a possibility that the lymphoma will return. If the lymphoma has not returned two to five years after the diagnosis, I think it is safe to say that the late toxicities and survivorship issues become much more important than the disease itself.
What are some concerns that ALCL patients entering survivorship tend to discuss with you?
Since initial chemotherapy includes a drug called Adriamycin (doxorubicin), we always follow a patient’s heart function. Late effects on the heart need to be kept in mind. There are different guidelines—mostly pediatric guidelines—about how often to check for cardiac complications, but I think that having a good internist, or a cardiologist, monitoring for late toxicity is very important.
Another issue, which is common to almost every chemotherapy regimen, is that patients can have damage to their bone marrow. Therefore, we need to ensure that a patient’s blood counts are checked at least once a year and also make sure their bone marrow does not have any late damage from the chemotherapy.
A very problematic concern, especially for younger patients, is that autologous stem cell transplants can result in an increased infertility rate. Therefore, reproductive issues need to be discussed from the very beginning. For men, they should consider sperm banking if they still wish to have children. For women, the possibility of infertility and early menopause need to be discussed.
Bone health is also important. Chemotherapy regimens do include high-dose steroids that can cause bone loss in some patients. Later in life, particularly for women, it is very important to be screened for things like osteoporosis.
Endocrine health, which refers to all the hormones in the body, is also important. This includes early menopause, weight gain, and changes in thyroid function, which are not specific to a particular treatment. Any kind of chemotherapy and autologous stem cell transplant will affect the hormones in the body.
People also feel there is an impact on memory and cognitive function after chemotherapy and an autologous stem cell transplant. Therefore, in addition to some of the side effects, I think one of the late effects is adjusting to a new rhythm with a different energy and focus that may or may not be the same as what the patient had before diagnosis.
Anxiety about recurrence is a very common psychological effect. Because of the intensive treatment, patients are typically exhausted afterwards and may be more emotional and more prone to depression. Anxiety is going to worsen that. Patients should know that there is help available.
Do you have any particular recommendations for patients?
The most important thing for patients to know is that they are not alone. It is very common to feel challenged when transitioning back to life after chemotherapy and/or a transplant, so they should reach out to support groups. The Lymphoma Research Foundation (LRF) is an excellent resource providing educational forums, Ask the Doctor workshops and the Lymphoma Support Network to name a few. At my center, we offer psychological support and have a psycho-oncology program that is very in tune with people who are transitioning to survivorship. Patients should not be afraid to reach out for professional help.
Can you discuss the importance of medical planning for ALCL patients who are in survivorship?
I think patients should be seen regularly by a physician and at least once a year by their oncologist. For my other lymphoma patients, after five to seven years, I advise them to transition back to their internist. With ALCL, and the T-cell lymphomas in general, it is a good idea to have both an internist/primary care physician and an oncologist. It is beneficial to have a team of people who know what the patient’s normal exam and their normal state of mind is so they can be more in tune with them if things change.
ALCL can also occur in childhood, and some people consider ALK-positive ALCL a pediatric disease. Ideally, if patients treated by a pediatric team can find an adolescent and young adult (AYA) clinic, that is a really good way to transition into adult oncology care. If they do not have that opportunity, I think it is important for them to ask their oncologist if they are familiar with ALCL and survivorship issues, and try to pick a medical team that at least has some knowledge of that.
Do you have any advice for ALCL survivors?
I would say to be encouraged and to stay connected to the lymphoma community. Treatment has really taken some major steps forward. We have drugs now for ALCL that were not available five years ago. Some of the new treatments are very targeted, which means that the drug only kills cells that have a specific target and therefore tend to spare normal tissues. Perhaps the best example is brentuximab vedotin, which is a drug that targets a protein called CD30 and then releases a very potent chemotherapy agent. CD30 protein is strongly expressed on ALCL cells. Other drugs that are approved by the FDA for T-cell lymphomas and have been tested in patients with ALCL include romidepsin, pralatrexate, and belinostat. These drugs are available because of clinical trials, and there is no way for us to move forward without more support for these trials.
How did you become involved with the Lymphoma Research Foundation, and why would you recommend that patients be involved with the organization?
I was asked to speak at one of LRF's educational forums in Chicago in 2002 and have been involved with their organization ever since. Now, I am on their Scientific Advisory Board and have promoted the organization to my patients because I think they do a fantastic job of providing education and a support network.
I think many patients are tempted to use the Internet and Google everything. To be honest, much of the information on the Internet does not apply to an individual patient. Having a resource like LRF is invaluable because they give you information that has been vetted by experts and is given in a way that most patients can understand.
Is there anything else you would like to add?
It is very important for patients to stay engaged in the lymphoma community when they are first diagnosed and to stay connected if they are in remission. Promoting research, either by participating in a clinical trial or supporting organizations that support trials, is very important. ALCL is a rare disease. The fact that we are even talking about survivorship shows that outcomes have improved and that people are surviving and overcoming this disease.