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Recurrent Hodgkin's Lymphoma: What To Know

Recurrent Hodgkin lymphoma means the cancer returns after treatment and remission. In many cases, further treatments can help achieve remission or a possible cure.

Hodgkin lymphoma (HL) is a type of cancer that begins in lymphocytes, a type of white blood cell that forms part of the lymphatic system.

Recurrent HL is the term for HL that returns after treatment and a period of remission. This article explores what recurrent HL means, including diagnosis, treatment options, and outlook.

Whether recurrent or in relapse, HL is the term for HL that returns after treatment.

According to the Lymphoma Research Foundation, recurrent HL means the cancer regrows or reappears after a period of remission.

According to a 2021 review, relapse can occur in up to 30% of people with the advanced stages of HL and 5–10% of those in the earlier stages of the disease where it has not spread.

If doctors suspect a HL relapse, they may carry out various tests, such as:

  • Blood tests: These measure the levels of blood cells people have, as lymphoma can cause low blood counts and other abnormalities in the blood that may indicate HL.
  • Scans: These include CT scans or ultrasounds to look for enlarged lymph nodes and to check if the cancer has spread.
  • Biopsy: This procedure involves taking a sample from a lymph node to test for lymphoma.
  • The test results will help doctors identify if the HL has returned, and if it has, what type and stage the lymphoma is and the best treatment strategy.

    Learn about the stages of lymphoma.

    To treat recurrent HL, people will usually have second-line chemotherapy treatment. This involves different drugs from the chemotherapy they may have received as part of the initial treatment. This may include single or combination drugs, such as:

  • ICE chemotherapy, which includes ifosfamide, carboplatin, and etoposide
  • gemcitabine-containing chemotherapy regimens, such as gemcitabine, vinorelbine, and pegylated liposomal doxorubicin, known as GVD
  • targeted chemotherapy, such as brentuximab and bendamustine
  • immunotherapy, such as nivolumab
  • Following chemotherapy treatment, people will then typically have a stem cell transplant.

    Learn more about chemotherapy for lymphoma.

    Treatments undergoing research

    Clinical trials are currently researching new treatment options for recurrent HL in addition to those available at the moment. Drugs under investigation include the following:

  • AB-205
  • anti-CD30-chimeric antigen receptor T cells
  • atezolizumab
  • bortezomib
  • camidanlumab tesirine
  • camrelizumab
  • carfilzomib
  • everolimus
  • ibrutinib
  • itacitinib
  • ipilimumab
  • lenalidomide
  • magrolimab
  • mocetinostat
  • pralatrexate
  • romidepsin
  • ruxolitinib
  • tislelizumab
  • umbralisib
  • People can speak with a doctor about the latest research and treatments for recurrent HL, whether any new treatments are available, or if they are interested in joining a clinical trial.

    Doctors may treat recurrent HL with a stem cell or bone marrow transplant.

    Doctors first use high dose chemotherapy to destroy both healthy and cancer cells in bone marrow.

    Following chemotherapy, a stem cell transplant replaces all these cells with healthy stem cells. Doctors collect these from the person undergoing the transplantation or a donor.

    For HL, there are two types of stem cell transplant that people may have:

  • Autologous: Doctors take stem cells from a person's blood or bone marrow to replace the cells. This is the most common form of transplant for HL.
  • Allogeneic: If an autologous transplant is ineffective, people have insufficient healthy stem cells for transplantation, or if the cancer has spread to bone marrow, individuals may have an allogeneic transplant. This uses stem cells from a donor.
  • Second-line treatments are usually effective in treating recurrent HL and may lead to a second remission or potentially cure the disease.

    The outlook may vary depending on various factors, including the stage of the disease. For earlier stages of HL, the 5-year overall survival may be 90%, and stage 4 cancer may be around 60%.

    Certain factors, such as age, overall health, and response to treatment, can also affect a person's outlook. There is some risk of secondary cancers forming from HL treatments, so attending regular follow-ups is important.

    People with recurrent HL may need to attend regular follow-up appointments to monitor their condition.

    If a person is in remission, they may require medical tests to assess if they need any further treatment. These tests may include blood tests and scans, such as CT or PET scans.

    Keeping hold of all medical records, test results, and information on treatments is important to help people monitor treatment progress. Follow-up care may continue for several years following HL treatment.

    There is no evidence that certain lifestyle or dietary changes can help with HL. However, focusing on healthy habits, such as regular exercise and following a balanced diet, can help support overall health.

    Here are answers to common questions about recurrent Hodgkin's lymphoma.

    Is recurrent Hodgkin's lymphoma curable?

    According to the Lymphoma Research Foundation, secondary treatments for recurrent HL are usually successful and may lead to a second remission or a cure.

    What happens if Hodgkin's lymphoma comes back?

    If doctors diagnose recurrent HL, they will assess the stage and type of lymphoma and the best treatment strategy. In most cases, treatment for recurrent HL includes chemotherapy and a stem cell transplant.

    What is the recurrence survival rate of Hodgkin lymphoma?

    According to a small 2021 study examining HL relapse for people with event-free survival, the 2-year overall survival and disease-specific survival were more than 90%.

    Other factors, such as the stage of the cancer, age, overall health, and type of treatment, may affect survival rates.

    How common is Hodgkin's lymphoma relapse?

    Initial treatment for HL has a high cure rate. Up to 30% of people with advanced stage HL may relapse after treatment results in complete remission. Additionally, 5–10% of people with limited stage HL may relapse.

    Most cases of recurrent classical HL usually occur within 3 years of the initial HL diagnosis, although some relapses can happen later. The risk of HL relapse may decrease after 2 years.

    Recurrent Hodgkin's lymphoma involves the cancer returning after treatment leads to remission.

    Treatment may involve high dose chemotherapy and stem cell transplants. Treatment may result in another remission or may even cure HL.


    Blood Tests Could Predict Poor CAR T-Cell Therapy Outcomes

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     As new cancer treatments become available, some of the most important ongoing research must look at ways to optimize those new approaches so that more patients can benefit from groundbreaking therapies. In work newly published in Blood Cancer Discovery, a journal of the American Association for Cancer Research, a team of collaborators from Roswell Park Comprehensive Cancer Center and Moffitt Cancer Center report the first strategy for  identifying before treatment which patients are at risk for poor outcomes from CAR T-cell therapy — pointing to opportunities to improve the safety and efficacy of this new and fast-growing class of cancer immunotherapies.

    "We determined that two common and easily measured blood tests can identify in advance which patients are at high risk for poor outcomes after treatment with CD19-targeted CAR T cells," says co-senior author Marco Davila, MD, PhD, Senior Vice President and Associate Director for Translational Research at Roswell Park. "We're excited because these findings not only help us to make CAR T-cell therapies work for more patients with hard-to-treat cancers, they also help us spare some patients from additional medications they don't need."

    Subscribe to Technology Networks' daily newsletter, delivering breaking science news straight to your inbox every day.

    Subscribe for FREE "Despite encouraging outcomes with CAR T-cell therapy for hard-to-treat B-cell lymphoma, some patients experience toxicity and poor outcomes. Our work determined that readily available lab tests for c-reactive protein and ferritin can identify which patients, pre-treatment, are at high risk for side effects and not responding to CD19-targeted CAR T-cell therapy," adds study first author Rawan Faramand, MD, Assistant Member of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt Cancer Center.

    CAR T, or chimeric antigen receptor T-cell therapy, has been FDA-approved for the treatment of many blood cancers, including some forms of lymphoma, leukemia and multiple myeloma. But these groundbreaking treatments, which enable a patient's immune cells to better target and eradicate cancer cells, can be associated with significant and sometimes-severe side effects.

    The new publication reports findings from a study of 146 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with the CAR T immunotherapy axicabtagene ciloleucel (also known as axi-cel, and sold under the brand name Yescarta) — all of whom had already received at least two prior lines of therapy for lymphoma. Nearly all the patients (93%) experienced cytokine release syndrome (CRS) following CAR T, and the majority (61%) developed immune effector cell-associated neurotoxicity syndrome (ICANS).

    "Chimeric antigen receptor T-cell therapy has changed the treatment paradigm for patients with relapsed/refractory hematologic malignancies," the authors write. "Despite encouraging efficacy, a subset of patients have poor clinical outcomes. We show that a simple clinically applicable model using pre-lymphodepletion CRP and ferritin" — two tests that measure key blood proteins — "can identify patients at high risk of poor outcomes."

    The team determined that patients with baseline serum blood levels of c-reactive protein (CRP) of at least 4 mg/dL and of ferritin of 400 ng/mL or higher represent those at highest risk for poor outcomes, including reduced progression-free and overall survival as well as higher rates of severe toxicities.

    While several studies have explored ways to characterize and measure the effectiveness of CAR T therapy following treatment, there was previously no widely available lab test or biomarker to rapidly identify patients at high risk for poor outcomes prior to CAR T-cell infusion.

    All 146 patients in the study were treated at a single center, Moffitt Cancer Center. The authors document two independent international cohorts that validate the approach, demonstrating that patients classified as low risk have excellent efficacy and safety outcomes.

    "Our algorithm allows us to identify patients who would be good candidates for prophylaxis, or additional therapies to control and prevent side effects, or for clinical studies to improve their outcomes," notes Dr. Davila. "It's an important tool that will help us personalize treatment for each patient."

    "Our group has previously shown that systemic inflammation and suppressive myeloid cells are associated with decreased efficacy in CAR T-cell therapy for lymphoma. Here we demonstrate that simple, and widely available, laboratory tests can similarly predict those patients with a decreased chance for success with CAR T. New strategies are needed for these patients, although CAR T remains the best therapeutic option for most patients we studied," says Frederick Locke, MD, Chair of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt Cancer Center. 

    Reference: Faramand RG, Lee SB, Jain MD, et al. Baseline serum inflammatory proteins predict poor CAR T outcomes in diffuse large B-cell lymphoma. Blood Cancer Disc. 2024. Doi: 10.1158/2643-3230.BCD-23-0056

    This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.


    What Are The Types Of Hodgkin's Lymphoma?

    Hodgkin's lymphoma is a type of cancer that starts growing in the white blood cells of the immune system. There are two different types and five subtypes, each with different characteristics.

    Hodgkin's lymphoma usually starts in the B cells, or lymphocytes. These are cells of the immune system that defend against bacteria and viruses by making proteins called antibodies. They travel through the body using a system of lymph nodes and lymph vessels.

    The main types of Hodgkin's lymphoma are classical Hodgkin's lymphoma (cHL) and nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL). The different types account for varying features of the changes to B cells, as well as different processes of growth and spread. The treatments for each type also vary.

    Read on to learn more about the types of Hodgkin's lymphoma. This article also looks at symptoms, diagnosis, and more.

    There are four subtypes of cHL:

    Together, these account for at least 90% of Hodgkin's lymphoma cases in developed countries.

    The presence of Reed-Sternberg cells, along with Hodgkin cells, defines cHL. Reed-Sternberg cells are large cells that often have more than one nucleus, which is the center of a cell that contains its genetic information.

    NLPHL is a separate type of Hodkin's lymphoma. It is less common.

    Nodular sclerosis Hodgkin's lymphoma (NSCHL)

    Lymph nodes with NSCHL have bands of scar tissue and tumors that grow as nodules. This subtype of Hodgkin's lymphoma is very treatable. It usually starts developing in the lymph nodes of the neck or chest.

    Around 70% of people with cHL have NSCHL. Males and females have a similar risk of developing this subtype. Likewise, people of any age can develop NSCHL. However, it occurs most often in young adults and teenagers.

    Mixed cellularity Hodgkin's lymphoma (MCCHL)

    In MCCHL, the lymph node tumors have Reed-Sternberg cells as well as other types. It is the second most common type, occurring in around 20–40% of people with Hodgkin's lymphoma.

    MCCHL is most common in the following groups:

  • males
  • children
  • older adults
  • people living with human immunodeficiency virus (HIV)
  • Lymphocyte-rich Hodgkin's lymphoma

    This is a rare subtype of cHL, developing in around 5% of people with cHL.

    Lymph nodes with lymphocyte-rich Hodgkin's lymphoma have a number of healthy B cells. It usually develops in just a few lymph nodes in the upper half of the body and is more common in males than females.

    As people with this type often receive an early diagnosis, the outlook for people with lymphocyte-rich Hodgkin's lymphoma is excellent, according to a 2023 review article.

    Lymphocyte-depleted Hodgkin's lymphoma

    This is the rarest subtype of cHL. Lymph nodes with lymphocyte-depleted Hodgkin's lymphoma do not have many healthy B cells. Instead, they have a high number of Reed-Sternberg cells.

    Older adults and people living with HIV have a higher risk of this subtype. It also has links to the Epstein-Barr virus (EBV), a herpes virus that can cause mononucleosis, or mono. Most often, physicians find lymphocyte-depleted Hodgkin's lymphoma in the abdomen, as well as in the bone marrow, liver, and spleen.

    Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL)

    This slow-growing type of Hodgkin's lymphoma leads to variants of Reed-Sternberg cells called popcorn cells. It occurs in around 5% of people with Hodgkin's lymphoma. It usually starts in the lymph nodes of the neck and underarms.

    People who are 30–50 years of age have the highest risk of NLPHL, and it is more common in males than females.

    Due to its slow growth, NLPHL can reoccur many years after treatment. It is highly treatable, but it can convert to the more aggressive non-Hodgkin's lymphoma in around 7% of people who have it.

    In developed countries, the most common type of Hodgkin's lymphoma is cHL. According to the American Cancer Society, it accounts for 9 in 10 cases of this cancer.

    NSCHL is the most common subtype. Around 7 in 10 people with Hodgkin's lymphoma have this subtype.

    Lymphocyte-depleted Hodgkin's lymphoma is the most aggressive subtype of Hodgkin's lymphoma. Physicians often find it at an advanced stage.

    Different subtypes of Hodgkin's lymphoma might be more likely in people of different sexes, age groups, and medical histories.

    However, the general risk factors for Hodgkin's lymphoma include:

  • having had mono
  • being age 20–30 years or older than 55 years
  • being male
  • having siblings who have had Hodgkin's lymphoma
  • having a compromised immune system, such as due to HIV, an autoimmune disease, or immune-suppressing medications after a transplant
  • It is best to contact a doctor if a person has concerns about the risk factors for Hodgkin's lymphoma.

    A group of symptoms known as "B symptoms" play a key role in diagnosing Hodgkin's lymphoma. These include:

    B symptoms become more likely in people with different subtypes, as follows:

  • About 4 in 10 people with NSCHL will have B symptoms.
  • B symptoms are common in people with MCCHL and lymphocyte-depleted Hodgkin's lymphoma.
  • These symptoms are rare in those with lymphocyte-rich Hodgkin's lymphoma.
  • Doctors usually diagnose Hodgkin's lymphoma using a biopsy. They will remove part or all of a lymph node and send it to a lab for testing.

    During lab testing, healthcare professionals examine the sample under a microscope. This is usually enough to identify the type. However, they will sometimes look for specific proteins that occur on the surfaces of Reed-Sternberg cells or other proteins that point to NLPHL.

    Learn more about how a biopsy works.

    An individual's overall health, the subtype of Hodgkin's lymphoma, and the cancer's aggressiveness can affect treatment choices. A doctor specializing in cancer treatment can provide more information on the best way to treat the condition.

    Most people with Hodgkin's lymphoma receive chemotherapy and radiation therapy. In chemotherapy, a cancer care team administers drugs that attack and kill cancer cells. In radiation therapy, cancer specialists use radioactive materials or lasers to destroy cancerous tissue.

    Some people with Hodgkin's lymphoma also receive immunotherapy treatments or stem cell transplants. Immunotherapy helps the immune system by targeting specific proteins on the surface of Hodgkin's cells or turning off safeguards that prevent the immune system from attacking certain cancer cells.

    Particularly hard-to-treat Hodgkin's lymphoma may respond to higher dose chemotherapy. However, this can destroy bone marrow, where blood cells develop. Stem cell transplants help cancer doctors give higher chemotherapy doses while giving bone marrow the chance to regrow.

    Learn more about chemotherapy for lymphoma.

    The two types of Hodgkin's lymphoma are classic and nodular lymphocyte-predominant. The classic type has four subtypes that vary depending on where they develop, who gets them, what symptoms they cause, and how aggressively they spread. The most common type is NSCHL. The most aggressive type is lymphocyte-depleted Hodgkin's lymphoma.

    Many types are diagnosable under a microscope after a biopsy, but further lab testing is sometimes necessary. This will help guide treatment among several other factors, including overall health and the stage of the cancer.

    A person's doctor can provide information about a person's treatment plan, which typically involves chemotherapy and radiation therapy.






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