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How We Treat Non-Hodgkin Lymphoma


  • Caron Jacobson, MD, discusses new treatment and research in lymphomas

  • Our Unique Approach

    Your care will involve the best treatments currently available, combined with new therapies based on research in our laboratories and elsewhere in the field of lymphoma treatment. We carefully consider an array of therapy options, including chemotherapy, radiation therapy, stem cell transplant, targeted therapies, immunotherapy, and clinical trials — many of which were developed by scientists in our own laboratories.

    The Adult Lymphoma Program at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) is part of Dana-Farber/Brigham and Women's Center for Hematologic Oncology, one of the world's largest and most respected treatment centers for patients with disorders of the blood or bone marrow. Hematological disorders can take many different forms, and your DF/BWCC care team has specialized knowledge in treating the various manifestations of non-Hodgkin lymphoma.

    Our laboratory-based work in lymphoma biology informs the use of new approaches to interfering with the pathways and abnormalities that drive lymphoma growth and survival. Each day, we work to translate findings in the laboratory into novel, less toxic treatments.

    Multidisciplinary Team

    At DF/BWCC's Adult Lymphoma Program, our experts manage your diagnosis and treatment plan as a close-knit team in order to decide what approach will best treat your particular disease at each stage. Because we are a highly specialized center, your testing, care, and follow-up are coordinated from your first appointment.

    Your care team includes medical oncologists, radiation oncologists, oncology nurses, nurse practitioners, stem cell transplant physicians and nurses when appropriate, research scientists, psychiatrists, nutritionists, and social workers. All of these team members work together to make sure your care is as seamless as possible.

    At our weekly lymphoma forum, specialists meet and discuss every new case. These specialists review your care plan to reach a consensus recommendation, which we share with you. We review particularly challenging cases at a division-wide conference with members from across specialty areas. They have expertise in standard therapies and emerging therapies and work to ensure that your care plan offers the best possible outcomes.

    Our team also connects with renal cancer specialists, oncocardiologists, and nephrologists when indicated to align your care.

    Personalized Treatment

    As a highly specialized program within DF/BWCC's Center for Hematologic Oncology, we focus on the distinct needs of patients with lymphoma. We provide a very personalized approach to your care. For example, if you are likely to have a specific side effect from a treatment, we take care to tailor your therapy to keep your quality of life at the center of the treatment plan.

    We view every patient as an individual, with unique needs and expectations. We take time to involve you and your family in each step of the treatment process. As you go through treatment phases, you and your family will have access to a wide range of support resources — from nutrition services to integrative therapies.

    Offering Expertise through Second Opinions

    • We believe there is great value for patients with suspected or diagnosed non-Hodgkin lymphoma to receive a second opinion. Many times, our pathologists render a different diagnosis from that of the referring doctor.
    • We routinely evaluate specimens sent to us from outside centers. These specimens are evaluated by our entire team, including our expert hematopathologists.

    Reasons to consider a second opinion include:

    • To confirm your diagnosis.
    • If you have received a diagnosis elsewhere and want to be treated at Dana-Farber/Brigham and Women's Cancer Center.
    • To determine the optimal therapy and timing of treatment.
    • To learn more about your cancer from specialists who are world leaders in this disease, and who have treated hundreds of other patients like you.
    • To learn if you're eligible for a clinical trial.

    Phone: 877-442-DFCI or 877-442-3324

    Online: Complete the Appointment Request Form.

    If you cannot travel to Boston in person, you can take advantage of our Online Second Opinion service.

    For Referring Physicians

    Because you, the referring physician, are an integral part of your patient's care team, we are committed to collaborating with you to provide the best care for your patient.

    If you are a physician and have a patient with diagnosed or suspected non-Hodgkin lymphoma, we look forward to working with you. Learn how to refer a patient.

    Treatment Approach

    A distinguishing area of our expertise is in determining how to integrate therapies, including identifying types of disease that do not require immediate treatment, determining the optimal cycles of chemotherapy, whether to change the combination of drugs during certain cycles, and whether to include radiation, biologic therapy, and/or a stem cell transplant. This is a highly complex process that requires expertise, and we continually reassess your treatment plan as your therapy progresses.

    We closely monitor you for treatment-related toxicities to ensure that the potential side effects from your therapy impact your life, hobbies, work, and interests as little as possible. Certain treatments may also heighten the risk of developing other conditions in the future. We are careful to factor this into treatment plans, especially for younger patients.

    • As part of your long-term treatment plan, we will screen you for possible side effects from treatment, such as heart disease and diabetes.
    • We will work with your primary care doctor to reduce these risks as much as possible.

    Treatment for Non-Hodgkin Lymphoma

    Today, patients have a number of therapy options, including different forms of chemotherapy, radiation therapy (radiotherapy), new oral drugs, and many other new agents that are accumulating at an incredibly fast pace. New treatment approaches, including immunotherapy (the use of therapies that spur the immune system) to attack cancerous lymphocytes, are showing considerable promise.

    Treatment for non-Hodgkin lymphoma depends on the subtype, and doctors may use a combination of chemotherapy and immunotherapy with or without radiation therapy. The majority of patients need more than one kind of therapy.

    The treatment plan is based on the cumulative diagnostic findings about your disease (including whether the cancer is indolent or aggressive), genomic and biological factors, symptoms, the likely progression of the disease, other medical conditions, and your own preference.

    • Indolent: Most patients respond well and have long-lasting remissions, but treatment does not cure the disease.
    • Aggressive: Treatment is usually a combination of chemotherapies and immunotherapy, often with the hope of curing disease. If there is a large mass, you may have radiation therapy with chemotherapy.

    For pregnant women with non-Hodgkin lymphoma, treatment is carefully chosen to protect the fetus. Treatment decisions are based on the mother's wishes, the stage of the disease, and the age of the fetus.

    Disease-Modifying Therapies

    Our researchers are studying the genomic, genetic, and epigenetic factors that characterize precancerous conditions at our Center for Prevention of Progression of Blood Cancers (CPOP).

    We created this Center to understand, at the molecular level, why some patients go on to develop disease, while others do not — and to develop non-toxic targeted therapies to prevent progression, or even eliminate the disease before it leads to symptoms. For example, we are examining how these factors play a role in preventing the progression of early-stage, asymptomatic low-grade lymphomas. This molecular information will allow us to accomplish two goals: to enhance our ability to determine a prognosis and to predict a patient's response to novel therapies.

    Contact CPOP

    If you are a patient — or the physician of a patient — who is willing to have samples of blood and cancer cells collected for the CPOP research effort during a medical appointment, or if you would like additional information, please email precursor@partners.org, or call 617-582-8664.

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    Treatments can include:

    Watchful Waiting

    Closely monitoring a patient's condition without giving treatment until signs or symptoms appear can be appropriate for some patients who have one of the slower-growing subtypes of B-cell and T-cell lymphoma. When these forms do need to be treated, we often use a less intensive regimen. An exception is Stage I indolent non-Hodgkin lymphoma, which can sometimes be cured with radiation therapy.

    Chemotherapy-Based Regimens

    Combination chemotherapy (treatments combining several chemotherapy drugs) is the backbone of most non-Hodgkin lymphoma therapy.

    Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells by either eliminating the cells or stopping them from dividing. The treatments combine several chemotherapy drugs. The way the chemotherapy is given depends on the type and stage of the cancer. Most of the drugs are given into the vein (intravenous, IV).

    For patients with indolent lymphoma, bendamustine and rituximab, rituximab, or R-CHOP (CHOP and rituximab) are generally used. Most patients respond well to these treatments and have long-term remissions.

    For patients with aggressive lymphomas, a combination chemotherapy regimen is generally used. Common regimens include:

    • CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) with or without rituximab
    • CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone) with or without rituximab
    • EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide and prednisone)

    Some patients may be at a particularly increased risk for the cancer returning, and for those patients, we sometimes take additional measures to prevent a recurrence by using high-dose chemotherapy. Steroid drugs may be added to relieve swelling and inflammation. Some patients may also require specialized approaches to treat lymphoma in the central nervous system, or to prevent it from affecting the central nervous system.

    Radiation Therapy

    The timing of when to use radiation therapy (radiotherapy) in relation to chemotherapy and stem cell transplant is very important. Our specialists have developed techniques to determine the radiation dose and volume that will give you the maximum benefits while minimizing long-term effects.

    Radiation therapy is highly individualized to determine the appropriate radiation therapy, treatment sites, and dose for each patient. The expertise of the radiation oncologist is critical to ensure your lymphoma is adequately treated while minimizing short and long-term effects of radiation.

    Radiation therapy can be the main treatment for some types of lymphoma if they are indolent Stage I or II, and this treatment can sometimes be curative. For more advanced or aggressive lymphomas, radiation therapy is sometimes used with chemotherapy.

    • Short-term side effects of radiation therapy can include skin redness and irritation, temporary hair loss, fatigue, mouth sores/sore throat/taste changes, dry mouth, nausea/vomiting, and diarrhea/cramps.
    • Late side effects of radiation therapy can include: cataracts, dry eyes and mouth, hypothyroidism, lung scarring, heart disease, sterility, and a second malignancy.

    Stem Cell Transplant

    Dana-Farber/Brigham and Women's Cancer Center has one of the largest and most experienced stem cell transplantation programs in the world. Stem cell transplantation can be an effective therapy for non-Hodgkin lymphoma in certain circumstances. High-dose chemotherapy with a stem cell transplant is used to destroy the diseased cells. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These stem cells restore the body's blood cells.

    Stem cell transplant is sometimes used either as part of initial treatment (mantle cell and T-cell) or when the cancer returns after conventional therapy (B-cell).

    The majority of stem cell transplants for non-Hodgkin lymphoma are autologous (using your own stem cells). In certain settings, we may recommend an allogeneic transplant, which uses stem cells from a family member, unrelated matching donor, or umbilical cord blood.

    Our lymphoma team is part of the transplant division, and we care for patients throughout their transplant procedure, allowing for a continuum of care for patients.

    Relapsed Disease

    Fortunately, there is an expanding number of treatment options available for people with relapsed lymphoma, and you will have the opportunity to speak with your physician about which regimen is most appropriate for you.

    Options can include:

    Immunotherapy

    Immunotherapy is frequently a part of treatment for relapsed disease. It is a treatment that uses substances made by the body or made in a laboratory to boost, direct, or restore the body's natural defenses against cancer. One example is CAR T-cell therapy, a form of immunotherapy that genetically modifies the patient's own T cells to improve the immune system's ability to fight cancer. CAR T-cell therapy has been approved by the FDA for some forms of relapsed or refractory aggressive non-Hodgkin lymphoma. Learn more about CAR T-cell therapy.

    Our group is also exploring, through clinical trials, whether checkpoint inhibitors such as nivolumab and pembrolizumab can help restore the immune system's ability to attack lymphomas. Vaccine therapy can be another type of biologic therapy.

    Monoclonal antibody therapy is a targeted treatment that uses antibodies made in the laboratory. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion or as an injection under the skin. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

    Targeted Therapy

    Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Targeted therapy is mostly used to treat relapsed disease. Targeted treatments that inhibit the cellular proteins important for the growth and survival of lymphoma include:

    • Proteasome inhibitors, such as bortezomib, are drugs that block proteasome (enzymes found in cells) activity, allowing defective proteins to accumulate. This can trigger cell death.
    • Lenalidomide is approved for mantle cell lymphoma.
    • Ibrutinib for mantle cell lymphoma, marginal zone lymphoma, and lymphoplasmocytic lymphoma.
    • Acalabrutinib for mantle cell lymphoma.
    • Idelalisib for follicular lymphoma.

    Once treatment starts for relapsed disease, you will be monitored closely for evidence that the treatment is working. Adjustments are made to enhance its effectiveness and your tolerance for the therapy.

    Investigational Approaches

    The Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) Adult Lymphoma Program operates a large and growing research program. We have approximately 25 clinical trials actively enrolling patients for the treatment of both newly diagnosed and relapsed/refractory lymphomas.

    All our clinical trials aim to increase the number of patients entering into remissions — particularly complete remissions — as well as increase the duration of these remissions. Another goal of the program's clinical research effort is to make the treatment of lymphoma more effective and specific, while also less toxic.

    Clinical trials provide a range of treatment options, including clinical trials of new chemotherapy combinations, new drugs in development, immunotherapies (including vaccines and CAR T-cell therapy), and molecularly and genetically targeted therapies.

    We also have clinical trials studying the immunologic response of patients after a stem cell transplant, the optimal sequencing of a stem cell transplant, and the use of biomarkers in relapsed or refractory patients.

    New Directions in Research

    Our translational research group focuses on the pathogenesis and treatment of all types of lymphoma.

    Other current research includes biological drugs and drugs directed at specific molecular targets, or with antibodies reactive against proteins on the surface of tumor cells. We are studying inhibitors of angiogenesis (new blood vessel development) and stimulators of the immune response.

    We are world leaders in the use of CAR T-cell therapy, a new form of cell therapy that deploys the patient's own immune cells (specially altered T cells) to more specifically target cancer cells, in combination with other therapies to improve duration of response. We are also studying the immunotherapy antibody pembrolizumab for certain types of B-cell and T-cell lymphomas.

    Specialized Approaches for Treating T-cell Subtypes

    There are many types of T-cell lymphomas, all of which are fairly rare and less common than B-cell lymphomas. About 10 to 15 percent of non-Hodgkin lymphomas in the United States are T-cell subtypes. Some T-cell lymphomas can be extremely aggressive; others are slow growing. Familiarity with each type is critical to determining the appropriate treatment.

    Smoldering T-Cell Lymphoma

    This type has abnormal T-cells in the blood without an increased number of lymphocytes in the blood. This lymphoma may involve the skin or lungs, but other tissues are not involved. It grows slowly, has mild symptoms, and has a good prognosis. Watchful waiting is often the treatment approach. Examples include T-cell large granular lymphocytic leukemia and some types of T-cell-prolymphocytic leukemia (T-PLL) and adult T-cell leukemia/lymphoma (ATLL).

    Nodal T-Cell Lymphoma (cancer is present in the lymph nodes)

    • ALCL (anaplastic large-cell lymphoma) is divided into two groups: ALK positive or negative, depending on whether cells have an abnormal form of a protein called anaplastic lymphoma kinase (ALK). It is characterized by enlarged lymph nodes in multiple regions in the body, or by tumors outside the lymph nodes in the bone marrow, intestine, muscle, liver, or spleen. Some ALCL presents only in the skin (primary cutaneous ALCL) and one type can be associated with prosthetic breast implants. Given the rarity of these ALCL sub-types, it is important to see a physician with experience treating these sub-types because they are managed differently than ALCL.
    • Cutaneous T-cell lymphomas (CTCL) are lymphomas that originate in the skin. CTCLs are a subset of peripheral T-cell lymphomas (PTCLs) because they are lymphomas of mature T-cells. However, these lymphomas are generally less aggressive, have a different prognosis, and have different treatment approaches than the aggressive PTCLs.
    • Primary cutaneous gamma-delta T-cell lymphoma is an extremely rare and aggressive disease that starts in the skin. As with other rare cancers, patients with gamma-delta T-cell lymphomas should discuss treatment options and potential clinical trials with their medical team.

    Non-nodal T-Cell Lymphoma

    • Hepatosplenic T-cell lymphoma is in the liver, spleen, and bone marrow. It usually affects young men and people who are immunosuppressed (such as with a rheumatoid illness). It is often confused with acute hepatitis. Symptoms include abnormal liver function and fever. Treatment is hyper-CVAD (modified fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) or IVAC (ifosfamide, etoposide/VP-16, and cytarabine) chemotherapy, followed by a stem cell transplant.
    • Enteropathy-associated T-cell lymphoma (EATL) has an association with Celiac disease (linked to chronic inflammation). Patients often are diagnosed after having a perforated small intestine. Treatment is CHOP or CHOP and etoposide/VP-16, followed by a stem cell transplant.
    • Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) occurs in the intestine, colon, or stomach. It is not associated with celiac disease. It is more common in Asian populations. Treatment is CHOP (cyclophosphamide, doxorubicin hydrochloride, oncovin, and prednisone) or CHOP and etoposide/VP-16, followed by a stem cell transplant.
    • Subcutaneous panniculitis-like T-cell lymphoma is characterized by the presence of multiple subcutaneous nodules all over the body. It can be confused with inflammation and rheumatologic disorders. It can be indolent but is treated like other forms of cutaneous lymphoma. Patients may only need oral methotrexate but occasionally have chemotherapy and a stem cell transplant. Both can be associated with hemophagocytic lymphohistiocytosis (HLH).
    • Extranodal NK/T-cell lymphoma is most common in Korea, Hong Kong, and other parts of Asia. It is always associated with an Epstein bar virus infection, and some genetic factors are likely. It usually affects the nose, septum, and palate. When localized, it has high cure rate with combined radiation therapy and chemotherapy, which are given at the same time. Treatment for stage III and IV is SMILE (dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide), followed by a stem cell transplant.

    Relapsed T-Cell Lymphoma

    Several agents are approved for the treatment of relapsed T-cell lymphomas. Pralatrexate (Folotyn) is approved for relapsed peripheral T-cell lymphoma. Romidepsin is approved for the treatment of relapsed or refractory CTCL and for the treatment of relapsed or refractory peripheral T-cell lymphoma. Belinostat is approved for relapsed/refractory peripheral T-cell lymphoma. Brentuximab is an immunotherapy that has been approved for anaplastic large-cell lymphoma and some cutaneous T-cell lymphomas.

    Leukemic T-Cell Lymphoma

    • T-LGL (T-cell large granular lymphocyte) is usually indolent and often does not need treatment right away. It is often associated with rheumatologic illness or other blood cancers. It can be over-diagnosed (often being confused with mono). Our Rapid Heme Panel can be useful to confirm or exclude a diagnosis. Treatment can include immunosuppressive therapy, such as oral methotrexate, cyclosporine, an immunomodulatory drug, or oral cyclophosphamide.
    • T-PLL (T-cell-prolymphocytic leukemia) is an aggressive disease marked by a rapidly rising white blood cell count, night sweats, and fever. It is characterized by abnormalities in the 8th or 14th chromosome. Our Rapid Heme Panel can be useful to confirm or exclude a diagnosis. T-PLL does not respond well to chemotherapy. Treatment may include antibody therapy. Stem cell transplant may be appropriate for some patients.
    • ATLL (Adult T-cell leukemia/lymphoma) has four subtypes: acute, lymphomatous, chronic, and smoldering. Acute and lymphomatous are fast- growing forms; chronic and smoldering are less aggressive. ATLL is associated with infection from the human T-cell lymphotropic virus type 1 (HTLV-1), and it is endemic to parts of the Caribbean, Central/South America, parts of Africa, and the Middle East. Most people acquire the virus as infants from breast milk or a blood transfusion. Treatment is aggressive chemotherapy, and those who respond may benefit from a stem cell transplant. Chronic or smoldering subtypes may not need treatment right away.

    Studying the Influence of Genetics in Lymphoma

    Our investigators are interested in learning more about the genes that contribute to lymphoma. This study will identify and study individuals with non-Hodgkin's lymphoma, Hodgkin's disease, or CLL/SLL who also have other family members with one of these diseases. We are particularly interested in families in which parents and children or brothers and sisters are both affected by lymphoma.

    Participants will provide medical history along with blood samples, saliva samples, and mouth swabs. All information can be provided by mail. No travel to Boston is necessary. Investigators will use the information you provide to increase our understanding of the causes of lymphoma.

    How to Participate

    If you are interested and believe that your family history makes you eligible, please email Harrison Bai at harrisonp_bai@dfci.harvard.edu. Please include the following information:

    • Your diagnosis (type of lymphoma)
    • Your family members who have also had lymphoma (i.e. mother, brother, daughter, etc.)
    • Please indicate if you are willing to sign a medical release for research purposes and/or are willing to donate a blood sample, saliva sample, and mouth swab for research purposes
    • Your contact information (name, email/phone number, mailing address)

    Your Care

    All outpatient therapy is provided at the Yawkey Center for Cancer Care at Dana-Farber Cancer Institute, one of the most advanced outpatient cancer centers in the country.

    If you need to be hospitalized during your care, or if you undergo stem cell transplantation, you will be admitted to Brigham and Women's Hospital (BWH) or the Dana-Farber Inpatient Hospital located within BWH. Your primary oncologist and nurse will closely monitor your care and will coordinate your care with the inpatient team and additional specialists, who will address any other symptoms you may be experiencing. This model ensures seamless care from the outpatient to the inpatient setting. Learn more about your stay.

    If radiation therapy is part of your care plan, Radiation Oncology has two units, one at Brigham and Women's Hospital and the other at Dana-Farber.