Hodgkins Lymphoma

Hodgkin lymphoma is a form of lymphoma that arises from B-cells of the immune system. It accounts for about 10% of lymphomas and often affects young adults, starting in lymph nodes in the neck or chest. Patients typically notice painless swelling of lymph nodes. As it spreads, fevers, night sweats, fatigue and itching can occur.

When examined under a microscope, Hodgkin lymphoma has an unusual appearance, with giant multi-lobed Reed-Sternberg cells embedded in inflammation. There are a few subtypes of classic Hodgkin lymphoma based on slight cell differences. A rarer form called nodular lymphocyte-predominant HL occurs more in men and younger patients.

To diagnose, an affected lymph node is biopsied. Imaging tests like PET/CT scans are done to see how far it has spread throughout the body. Treatment depends on the stage, but usually involves chemotherapy regimens like ABVD or BEACOPP. Radiation may be added to treat nodes with bulky disease.

The prognosis for Hodgkin lymphoma is better than other lymphomas when diagnosed early. It is often curable even in later stages if it responds well to initial chemo and radiation. About 90% of patients with early stage I-II Hodgkin lymphoma survive at least 5 years. Recurrence is still a risk requiring follow-up. New immunotherapies are now being added to treat high-risk Hodgkin disease as well.

In summary, Hodgkin lymphoma is a relatively uncommon cancer of the immune system that tends to affect younger patients. Despite its often aggressive nature, cure is frequently achievable with modern combined treatments when caught early. Continued research aims to further improve outcomes.

Executive Summary

  • Hodgkin Lymphoma Basics Hodgkin lymphoma is a cancer that starts in the immune system's B-cells, often affecting young adults. It usually begins in lymph nodes in the neck or chest, causing painless swelling. The disease is characterized by the presence of large, abnormal Reed-Sternberg cells, which are crucial for diagnosis.

  • Diagnosis and Staging Doctors diagnose Hodgkin lymphoma through a lymph node biopsy, looking for Reed-Sternberg cells. Imaging tests like PET/CT scans help determine how far the cancer has spread. The disease is staged from I to IV based on its extent, with additional subcategories providing more detail about symptoms and affected areas.

  • Types and Risk Factors There are several subtypes of Hodgkin lymphoma, with classic Hodgkin lymphoma being the most common. Risk factors include age (young adults and those over 55), male gender, family history, and certain viral infections like Epstein-Barr virus. A weakened immune system can also increase the risk.

  • Treatment Approaches Treatment typically involves chemotherapy, often using regimens like ABVD or BEACOPP. Radiation therapy may be added, especially for early-stage disease. For more advanced or resistant cases, stem cell transplants and newer targeted therapies like brentuximab vedotin or PD-1 inhibitors may be used.

  • Chemotherapy Details The ABVD regimen, a common treatment, combines four drugs: Adriamycin, Bleomycin, Vinblastine, and Dacarbazine. Each drug works differently to kill cancer cells or stop their growth. Treatment is usually given in cycles over several months, with side effects like fatigue, nausea, and lowered blood counts being common.

  • Radiation Therapy Radiation uses high-energy beams to target cancer cells. Modern techniques like intensity-modulated radiation therapy allow for precise targeting of tumors while sparing healthy tissue. Side effects can include fatigue, skin irritation, and potential long-term risks to organs near the treated area.

  • Immunotherapy Advancements Newer treatments like PD-1 inhibitors (e.g., nivolumab and pembrolizumab) boost the immune system's ability to fight cancer cells. These drugs have shown promising results in patients whose disease has returned after initial treatment. However, they can cause unique side effects related to an overactive immune response.

  • Stem Cell Transplant For some patients, especially those with relapsed disease, high-dose chemotherapy followed by a stem cell transplant may be recommended. This intensive treatment aims to eliminate remaining cancer cells and restore the body's ability to produce healthy blood cells.

  • Prognosis and Survival Rates With modern treatments, the outlook for Hodgkin lymphoma is generally good. Early-stage disease has 5-year survival rates of 90-95%, while advanced stages still see rates of 80-90%. However, factors like the patient's age, disease stage, and response to initial treatment can affect individual outcomes.

  • Supportive Care Managing side effects and maintaining quality of life during treatment is crucial. This can involve medications for nausea or low blood counts, nutritional support, and psychological counseling. Good supportive care helps patients complete their planned treatment course.

  • Research Scientists continue to study Hodgkin lymphoma to improve treatments and understand the disease better. Recent research has revealed how cancer cells manipulate nearby immune cells, potentially leading to new treatment strategies. This ongoing work aims to further increase cure rates and reduce treatment side effects.

Key differences between lymphoma and leukemia

  • Lymphoma involves cancerous lymphocytes that form solid tumors or masses, usually in the lymph nodes or other lymphatic tissue. Leukemia involves cancerous blood-forming cells (like lymphocytes or myeloid cells) that circulate in the blood and bone marrow.

  • Lymphoma is categorized as Hodgkin lymphoma or Non-Hodgkin lymphoma. Leukemia is categorized as acute or chronic, and lymphocytic or myelogenous.

  • Lymphoma tends to present as enlarged lymph nodes, which are solid tumor masses. Leukemia does not usually cause lymph node enlargement.

  • Lymphoma may compress or invade local structures as it spreads in the lymph system and body. Leukemia does not usually form solid masses but rather crowds out normal blood cells.

  • Lymphoma treatment involves chemotherapy, radiation to affected nodes, immunotherapy, etc. Leukemia treatment focuses on systemic chemotherapy, bone marrow transplants, targeted drugs.

  • Prognosis and outcomes differ between lymphomas and leukemias based on specific subtypes. Some lymphomas like Hodgkin disease are often curable. Acute leukemias have poorer outcomes.

  • Both lymphoma and leukemia arise from lymphocytes, but they have distinct patterns of behavior, spreading, diagnosis, and response to treatment due to one being solid and one liquid.

So in summary, while both are cancers of lymphocyte origin, the patterns of growth and management differ between lymphomas which form tumor masses versus leukemias which circulate in blood and marrow.

A more comprehensive overview of Hodgkin lymphoma

Definition and Epidemiology

  • Hodgkin lymphoma is a type of B-cell lymphoma that accounts for about 10-15% of all lymphoma cases

  • It has an annual incidence of about 2.2 cases per 100,000 people in Western countries

  • Slightly more common in males, with a typical age of onset between 20-40 years old

  • Incidence is also increased in older adults over age 55

Pathogenesis

  • Originates from germinal center or post-germinal center B cells that have undergone malignant transformation

  • Hallmark is the presence of giant multinucleated Reed-Sternberg cells and mononuclear Hodgkin cells

  • These Hodgkin/Reed-Sternberg cells secrete factors that recruit other inflammatory cells, suppress the immune system, and promote tumor growth

Subtypes

  • Classic Hodgkin Lymphoma (~95% of cases)

  • Nodular Sclerosis (~80% of classic HL) - most common overall

  • Mixed Cellularity (~15% of cHL)

  • Lymphocyte-rich (~5% of cHL)

  • Lymphocyte-depleted (<1% of cHL)

  • Nodular Lymphocyte-Predominant Hodgkin Lymphoma (~5%)

Diagnosis

  • Excisional biopsy of affected lymph node

  • Microscopic examination showing Reed-Sternberg cells and typical pattern

  • Immunohistochemistry (CD15, CD30, CD20)

  • PET/CT scan for staging

  • Bone marrow biopsy if advanced stage

Treatment

  • Early stages: Chemotherapy (ABVD) + involved field radiation

  • Advanced stages: More aggressive chemo (BEACOPP) +/- radiation

  • Relapsed/refractory: High-dose chemo + autologous stem cell transplant

  • Novel therapies: Brentuximab, immunotherapy

Symptoms

  • Painless lymph node enlargement, often in neck or mediastinum

  • Systemic B symptoms in ~1/3 of patients - fevers, night sweats, weight loss

  • Pruritus, fatigue, alcohol-induced pain

Staging

  • Stage I-II: Single node or node region involved

  • Stage III-IV: Multiple lymph nodes on both sides or extranodal spread

Prognosis

  • 5-year survival ~90% for stage I-II, 70% for stage III, 60% for stage IV

  • Pediatric cases often have better outcomes

  • Relapse or progressive disease worsens outcomes

In summary, Hodgkin lymphoma is an uncommon B-cell lymphoid malignancy with characteristic Reed-Sternberg cells and a favorable prognosis when diagnosed early and treated appropriately. However, relapsed or refractory disease remains a challenge.

What is Hodgkin Lymphoma?

Hodgkin lymphoma is a distinct subtype of lymphoma, a cancer that emerges from the lymphatic system. This system, an intricate network of vessels, nodes, and organs, acts as a cornerstone of the body's immune defense mechanism. The primary role of the lymphatic system is twofold: first, to combat infections and various diseases by transporting and filtering harmful entities, and second, to circulate a fluid called lymph. This clear fluid houses lymphocytes, a pivotal white blood cell variety that plays a role in immune responses. However, when lymphoma strikes, these very lymphocytes deviate from their normal behavior, turning malignant and proliferating at an abnormal, unchecked rate.

The hallmark of Hodgkin lymphoma, setting it apart from a broad spectrum of lymphomas, notably the non-Hodgkin lymphomas, is the manifestation of a unique cell: the Reed-Sternberg cell. When observed under the microscopic lens, these cells are conspicuously large and bear a malignant nature. Their distinctive appearance, often described as "owl-eyed," makes them a critical factor in diagnosing Hodgkin lymphoma from biopsy samples of affected tissue.

Upon delving into the symptomatology of Hodgkin lymphoma, a myriad of clinical presentations becomes evident. One of the most overt signs is the painless enlargement of lymph nodes, particularly noticeable in accessible regions such as the neck, armpits, or groin. This swelling stems from the accumulation of the abnormal lymphocytes within the lymph nodes. Furthermore, systemic symptoms often accompany this disease, casting a broader shadow of discomfort over the affected individuals. They might grapple with persistent, unyielding fatigue that hampers daily activities, fevers that spike without a clear source of infection, and chills that seem out of place. Night sweats, so intense that they drench sleepwear and bedding, are also a common complaint. Unanticipated weight loss, devoid of changes in diet or exercise, often raises alarm bells. Some individuals also report a peculiar symptom: an unrelenting itchiness that affects vast expanses of the skin. Another curious observation is an increased sensitivity to alcohol; patients might experience pain in their lymph nodes following alcohol consumption, though this symptom is less common.

The cumulative presence of these symptoms, combined with medical imaging and biopsy results, typically guides the path to a definitive diagnosis of Hodgkin lymphoma.

How is it Diagnosed?

Doctors do a biopsy, meaning they take a sample of an enlarged lymph node to examine under a microscope. This shows giant Reed-Sternberg cells which are typical of Hodgkin lymphoma. Imaging tests like PET/CT scans allow doctors to see how far it may have spread in the body.

Who Gets It?

Hodgkin lymphoma, a cancer stemming from lymphocytes or white blood cells, has several associated risk factors, though the exact cause remains elusive. Notably, merely having one or more risk factors doesn't guarantee the development of the disease, and conversely, many diagnosed with Hodgkin lymphoma might not have any recognized risk factor.

Age and gender play a role in its incidence. Hodgkin lymphoma frequently affects young adults, typically in their 20s, and older adults over the age of 55. Additionally, the disease has been observed to be slightly more prevalent in males than in females.

Infections, particularly by the Epstein-Barr Virus (EBV), which is responsible for mononucleosis, can increase the risk of Hodgkin lymphoma. Similarly, familial ties to the disease can indicate an elevated risk. Individuals with a sibling, especially a twin, who has had Hodgkin lymphoma are at a heightened risk. This risk is slightly reduced, but still present, if a parent or child has been diagnosed with the condition.

The immune system's functionality is crucial. A compromised immune system, resulting from diseases like HIV/AIDS or from immune-suppressing medications taken post-organ transplant, can make an individual more susceptible to Hodgkin lymphoma. Similarly, those with autoimmune conditions, where the immune system attacks the body's tissues — like rheumatoid arthritis or lupus — may have an increased risk.

Geographic location and socioeconomic factors play a part too. Hodgkin lymphoma diagnoses are more frequent in areas like the U.S., Canada, and northern Europe. Additionally, some studies have linked a higher socioeconomic status to an increased incidence of the disease.

Individuals who have overcome certain types of cancers, like breast or lung cancer, and underwent radiation therapy during their treatment might face a heightened risk of developing Hodgkin lymphoma later on.

Lifestyle choices and physical attributes have also been scrutinized. There's an ongoing discussion, albeit not yet concrete, suggesting that individuals with increased body weight and height might be more at risk.

Environmental exposures, although not definitively linked, have been under the lens for potential risk. Some hypotheses suggest that exposure to specific chemicals or pesticides could be tied to the development of Hodgkin lymphoma.

Lastly, there's an interesting observation regarding previous infectious diseases. Some research suggests that a history of particular infectious diseases, such as measles, might potentially reduce the risk of Hodgkin lymphoma, though this remains an area of active study.

History

Hodgkin lymphoma has been recognized as a distinct disorder for over 180 years, though our understanding of this disease has evolved tremendously over time.

In 1832, British physician Thomas Hodgkin first described abnormal enlargements of lymph nodes and spleen in seven patients. He recognized these as a unique condition, different from other diseases.

It wasn't until the early 1900s that William Reed, Dorothy Reed and Carl Sternberg first identified and characterized the unusual giant cells seen in Hodgkin lymphomas under the microscope, now called Reed-Sternberg cells. This key observation linked Hodgkin’s descriptions to a specific cancer of the lymphatic system.

By the mid-1900s, knowledge advanced on the typical patterns of lymph node involvement, spread to other organs, and association with systemic "B symptoms" like fever and night sweats. Classification systems were devised to categorize Hodgkin lymphoma into subtypes based on microscopic differences.

Treatment originally relied on radiation therapy alone, providing only temporary benefit. It wasn't until the 1960s and 1970s that combination chemotherapy regimens emerged, such as the MOPP regimen, that turned Hodgkin lymphoma into a potentially curable disease in many patients. More chemotherapy combinations followed like ABVD and BEACOPP with refined radiation techniques.

In recent decades, positron emission tomography became invaluable for accurate staging and treatment response monitoring. Additionally, novel therapies like immunotherapy drugs have further improved outcomes for patients with high-risk or refractory Hodgkin lymphoma.

Over nearly two centuries, Hodgkin lymphoma transformed from an obscure, fatal disorder to one of the more successfully treated hematologic malignancies, though much work remains to further improve patient outcomes and cure rates.

Causes

Although the exact cause of HL is not fully understood, multiple factors are thought to contribute to its development. The interplay of these factors in genetically susceptible individuals leads to the transformation of normal lymphocytes into cancerous cells.

Genetic mutations

Some HL cases can be attributed to inherited or acquired genetic mutations. These mutations can affect genes responsible for the regulation of lymphocyte growth and division. Additionally, alterations in DNA repair genes can increase the risk of HL, as these genes play a critical role in repairing damaged DNA, preventing the accumulation of mutations that can lead to cancer.

Environmental triggers

Certain environmental factors, such as exposure to toxins or radiation, may increase the risk of developing HL. However, the role of infectious agents other than EBV in HL remains unclear.

Familial susceptibility

A small proportion of HL cases have a family history of the disease, indicating an inherited genetic predisposition. HL risk is also elevated in individuals with certain diseases, such as glioma and autoimmune lymphoproliferative syndrome.

Viral infections

The Epstein-Barr virus (EBV) has been linked to some cases of HL. EBV can infect B-cells, a type of lymphocyte, and potentially contribute to their transformation into cancerous Reed-Sternberg cells. Other viruses may also play a role in the development of HL, but more research is needed to confirm these associations.

Gender

HL is slightly more common in males, although the reasons for this disparity are not well understood. Estrogen levels in women may provide some protective effects against the development of HL.

The development of HL is likely the result of a complex interplay between genetic risks, viral triggers, immune system dysregulation, and environmental exposures in genetically susceptible individuals. More research is needed to fully understand the interactions between these factors and their role in the development of HL.

Immune dysfunction

A dysfunctional immune system can contribute to the development of HL. For example, imbalances in immune function, such as unregulated cytokine production, can promote the growth of lymphoma cells. Ineffective tumor immunosurveillance, where the immune system fails to recognize and eliminate cancer cells, may also enable HL to develop and progress.

Age

HL is most commonly diagnosed in young adults between the ages of 15 and 40 and in older adults over age 55. Changes in immune function with aging may play a role in the development of HL in older individuals.

Diagnosis

The first signs of Hodgkin lymphoma often come from a patient noticing swellings or lumps in lymph node areas like the neck, under the arms, or in the groin region. These are usually painless. A doctor examining the patient will feel these enlarged lymph nodes during a physical exam.

To determine if the node enlargement is actually due to Hodgkin disease, the doctor will recommend a lymph node biopsy. This involves using a thin needle to extract a small tissue sample from the enlarged node. The sample is then examined under a microscope by a pathologist.

The presence of very large, abnormal Reed-Sternberg cells within the lymph node tissue is the hallmark of Hodgkin lymphoma. These oversized, multi-lobed cells surrounded by inflammatory cells confirm the diagnosis when seen on pathology.

Once Hodgkin is diagnosed, imaging tests like PET/CT scans and sometimes MRI are needed to stage the disease - figuring out how far it has spread throughout the body beyond the original node site. Blood tests also help assess a patient's overall health status.

In some cases, the doctor may recommend a bone marrow biopsy to make sure the cancer has not entered the marrow space. Thankfully, Hodgkin only spreads to bone marrow less than 10% of the time.

So in summary, a step-wise approach of physical exam, lymph node biopsy, lab tests, and imaging provides oncologists with the information they need to both definitively diagnose Hodgkin lymphoma and determine appropriate next steps for treatment.

Staging

Staging is a critical component of the diagnosis, treatment planning, and prognosis determination for Hodgkin lymphoma. It involves numerous tests to create a detailed "map" of where the cancer is located, how far it has spread, and what areas of the body are involved.

Staging tests may include CT scans of the chest, abdomen and pelvis, PET scans, MRIs, bone marrow biopsies, lymph node biopsies, and more. These tests allow doctors to assign a stage from I to IV based on the extent of spread. Within some stages, substages from A to E provide additional detail on affected sites.

Stage I

Stage I indicates the Hodgkin lymphoma is limited to a single lymph node region. The involved lymph node region could be cervical, axillary, inguinal or another area. Or, in rare cases, the cancer has invaded a single extralymphatic organ or tissue without involving any lymph nodes. This is designated Stage IE. The cancer has not yet spread in Stage I.

Stage IIB

Cancer is in two or more lymph node regions on the same side of the diaphragm, plus there is a tumor mass in the chest that is over one-third the width of the chest or over 10 centimeters. The large chest tumor mass indicates more advanced disease.

Stage IIIA

Cancer is in lymph nodes above and below the diaphragm. The spleen may also be involved.

Stage II

Stage II means the Hodgkin lymphoma is present in two or more lymph node regions on the same side of the diaphragm, the muscle under the lungs separating the chest and abdomen. Stage II has three subcategories:

Stage IIE

Cancer has spread locally from the lymph nodes to nearby tissues or organs on the same side of the diaphragm. For example, it may have extended to the lungs or spleen.

Stage IIIB

Cancer is in lymph nodes above and below the diaphragm and has also spread to the spleen, which is considered an extralymphatic site.

Stages A and B

The stages may also have an "A" or "B" designation based on the presence of B symptoms - unexplained fever over 38°C, drenching night sweats, or unexplained weight loss exceeding 10% of body weight in the last 6 months. "B" designation indicates a poorer prognosis.

Stage IIA

Cancer is in two or more lymph node regions on the same side of the diaphragm. Common sites include the neck, chest, armpit or groin areas.

Stage III

In Stage III, the Hodgkin lymphoma is present in lymph node regions on both sides of the diaphragm. It indicates further spread of the disease into the chest and abdomen. Stage III has two substages:

Stage IV

Stage IV Hodgkin lymphoma has disseminated, or spread, beyond the lymphatic system to other organs. Common sites include the liver, bone marrow, lung and bones. Stage IV indicates advanced disease that has spread to distant sites via the bloodstream or lymphatic system.

Prognosis Factors

In addition to stage, other prognostic factors guide treatment. These include the patient's age, gender, blood counts, histological subtype, sites and size of affected lymph nodes or tumor masses, and markers like sedimentation rate. Doctors incorporate all this information to determine optimal treatment.

CT scans of the chest, abdomen and pelvis

This provides 3D image views of the internal lymph nodes and organs to identify size, number and location of affected nodes or masses. IV contrast is often used to enhance visualization.

Lymph node biopsy

A surgical biopsy of an accessible swollen node is done to confirm Hodgkin lymphoma diagnosis prior to staging.

Pulmonary function tests

These assess lung capacity prior to potential lung radiation therapy.

PET (positron emission tomography) scans

This imaging test reveals metabolic activity in tissues and can identify cancerous areas that may not show up on CT scans. PET scans are often combined with CT.

Laboratory tests

Complete blood counts, liver function tests, erythrocyte sedimentation rate and other labs provide additional data on the cancer's effects.

MRI scans

Magnetic resonance imaging provides enhanced soft tissue views that can further evaluate the chest, abdomen or bone marrow involvement.

Stage migration

Advances in diagnostic imaging now allow detection of increasingly smaller disease volumes. This can lead to "stage migration"- where some cases once classified as stage I are now stage II thanks to improved test sensitivity. Stage migration must be considered when evaluating long-term outcome data. Historical outcomes may seem worse than today's early-stage cases now that imaging provides more comprehensive staging.

Bone marrow biopsy

A core sample of bone marrow is extracted, usually from the hip bone, to check for cancerous cells that may have spread to the marrow.

Cardiac imaging

Echocardiogram or MUGA scans evaluate heart function if Adriamycin chemotherapy may be used.

The information from all these tests allows oncologists to pinpoint the sites of cancer involvement for accurate staging and treatment targeting.

Treatment

Chemotherapy Regimens

ABVD Regimen

The ABVD chemotherapy regimen consists of four drugs:

Adriamycin (Doxorubicin)

  • Anthracycline antibiotic that intercalates DNA strands and inhibits DNA/RNA polymerase

  • Generates free radicals that damage DNA and cell membranes

  • Given as intravenous infusion, typical dose 25-35 mg/m2 on Day 1 and Day 15 of each cycle

  • Red color can turn urine red for 1-2 days after dosing

  • Cardiotoxicity and bone marrow suppression are primary toxicities

Bleomycin

  • Glycopeptide antibiotic that induces DNA strand breaks leading to apoptosis

  • Given intravenously or intramuscularly, typical dose 10 units/m2 on Day 1 and Day 15

  • Pulmonary toxicity with risk of pneumonitis or fibrosis is main side effect

  • Requires lung function monitoring, avoid in smokers

Vinblastine

  • Vinca alkaloid that binds tubulin, preventing microtubule formation needed for mitosis

  • Given as IV infusion, typical dose 6-8 mg/m2 on Day 1 and Day 15

  • Neurotoxicity includes constipation, numbness, weakness

  • Myelosuppression occurs, monitor blood counts

Dacarbazine (DTIC)

  • Alkylating agent that attaches alkyl groups to DNA bases, causing crosslinks and strand breaks

  • Given IV, typical dose 375 mg/m2 on Day 1 and Day 15

  • Hepatotoxicity and myelosuppression can occur

  • Nausea is common side effect, requiring antiemetic premedication

Typical ABVD administration schedule:

  • Every 2 weeks for 6-8 cycles

  • Each cycle lasts 28 days

  • Adriamycin and vinblastine given on Days 1 and 15

  • Bleomycin and DTIC given on Days 1 and 15

  • Growth factor support to counter neutropenia

  • Anti-nausea medication routine

BEACOPP Regimen

Adds etoposide, cyclophosphamide, procarbazine to the ABVD regimen:

Etoposide - topoisomerase inhibitor that causes DNA strand breaks and apoptosis Cyclophosphamide - alkylating agent that crosslinks DNA strands Procarbazine - alkylating agent that attaches methyl groups onto DNA

Higher intensity dosing used:

  • Baseline dosing x 2 cycles then escalated dosing x 2 cycles, continuing alternation for total of 6-8 cycles

Toxicities include severe myelosuppression, mucositis, infertility risk, secondary leukemia risk. Requires growth factor support and hospitalization.

Stanford V Regimen

Combines multiple chemo drugs plus radiation:

  • Doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone

  • 12 weeks total - 8 weeks chemotherapy then 4 weeks radiotherapy with lower dose chemotherapy

Attempts to reduce pulmonary toxicity by omitting bleomycin and procarbazine. Still requires substantial supportive care and hospitalization.

Chemo Administration

Chemotherapy is typically given intravenously, although some drugs are in pill form. A port-a-cath central line may be placed for easier administration and blood draws. Pre-meds to prevent reactions are given. Most chemo regimens require hospital visits for each cycle, usually every 2-4 weeks.

Common chemo side effects include:

  • Low blood counts - Increases risk of infection, anemia, bleeding. Growth factor drugs like Neupogen can help.

  • Nausea and vomiting - Powerful anti-nausea drugs like Zofran and Emend help prevent this.

  • Fatigue - Daily activities may be limited, requiring more rest. Light exercise can help conserve energy.

  • Increased infection risk - Antibiotic prophylaxis is sometimes used, along with protective isolation procedures. Patients should avoid sick contacts.

  • Hair loss - Scalp cooling caps can reduce hair loss for some patients. Hair regrows after chemo ends.

  • Mouth sores - Good oral hygiene is essential. Salt water and numbing rinses help relieve pain.

  • Loss of appetite - Small, frequent meals and fluids are encouraged. Appetite stimulants and nutritional supplement drinks can help maintain weight and strength.

Targeted Therapies

Brentuximab vedotin (Adcetris)

  • Antibody-drug conjugate that binds to CD30 on Hodgkin lymphoma cells

  • Delivers the chemotherapy drug monomethyl auristatin E (MMAE) directly into tumor cells

  • Once inside cells, MMAE disrupts microtubule assembly leading to apoptosis

  • Given by intravenous infusion every 3 weeks

  • 75% response rates in relapsed/refractory Hodgkin lymphoma

  • Peripheral neuropathy is common side effect

  • Being studied as part of frontline therapy combinations

These targeted therapies provide options for relapsed Hodgkin lymphoma and are transforming the treatment landscape by improving outcomes compared to conventional chemotherapy alone. Ongoing research is exploring how best to incorporate them into frontline regimens.

Potential Side Effects

  • Peripheral neuropathy - Numbness, tingling, pain in hands/feet due to damage to peripheral nerves. Dose reductions or treatment breaks may be required.

  • Neutropenia - Low neutrophil counts raise infection risk. Growth factor support is recommended.

  • Fatigue, nausea/vomiting - Often manageable with antiemetics and supportive care.

  • Diarrhea, abdominal pain - Can occur and may require anti-diarrheal medications.

  • Skin rash - Mild rash may appear in some patients. Topical steroids can help.

  • Infusion-related reactions - Flushing, low blood pressure, fever, chills during infusion. Premedication helps.

PD-1 Inhibitors (Opdivo, Keytruda)

  • Nivolumab and pembrolizumab are PD-1 blocking antibodies

  • Hodgkin lymphoma cells express PD-L1 which binds PD-1 on T cells to inhibit immune response

  • By blocking PD-1, the drugs boost T cell activity against cancer cells

  • Given by intravenous infusion every 2-3 weeks

  • Response rates around 65-70% in relapsed/refractory Hodgkin lymphoma

  • Immune-related adverse effects include colitis, thyroiditis, pneumonitis

  • Being evaluated as part of first-line therapy for advanced stage disease

Brentuximab vedotin (Adcetris) side effects

Careful monitoring and prompt side effect management are important to allow patients to stay on these effective targeted therapies long-term.

PD-1 Inhibitors (Opdivo, Keytruda) side effects

  • Immune-related adverse events:

    • Colitis - Inflammation of colon, may cause diarrhea, abdominal pain. Steroids used to treat.

  • Hypothyroidism or hyperthyroidism - Thyroid function monitoring recommended.

  • Pneumonitis - Inflammation of lungs, leading to cough, shortness of breath. Corticosteroids used to manage.

  • Rash, pruritus - Immune-driven skin effects. Topical steroids, antihistamines used as needed.

  • Fatigue, decreased appetite - Supportive care helps manage constitutional symptoms.

  • Liver enzyme elevations - Periodic liver function monitoring advised. Hold treatment if high.

Radiation Therapy

Types of Radiation Therapy

  • External beam radiation: High energy x-rays targeted at lymphoma nodes and sites from outside the body. Most common form used.

  • Intensity-modulated radiation therapy (IMRT): Advanced form using computerized treatment planning and delivery techniques to sculpt dose around the tumor while sparing normal tissue. Highly conformal fields allow higher target doses.

  • Proton beam therapy: Uses proton particles instead of x-rays. Protons deposit dose at precise tumor depth, reducing exit dose and side effects. Growing option for lymphoma.

  • Total body irradiation (TBI): Patient's entire body is treated with lower dose radiation, often prior to stem cell transplant. Increased toxicity.

Treatment Planning

  • CT simulation used to map treatment area and normal structures

  • Immobilization devices customize positioning

  • Radiation oncologist contours target volumes and organs to avoid

  • Highly conformal plan maximizes dose to involved nodes while minimizing exposure to lungs, heart, breasts, etc.

Delivery Schedule

  • Early stage: Radiation alone with 15-30 treatments over 3-5 weeks

  • Advanced stage: 20-30 radiation treatments given in 4-6 weeks, with lower dose chemotherapy concurrently

Side Effects

  • Fatigue - Worsens over treatment course. Conserving energy helps.

  • Skin irritation - Aloe vera, topical steroids provide relief.

  • Low blood counts - Nadirs occur about 2 weeks after radiation ends.

  • Swallowing difficulty - If neck/throat treated. Soothing liquids and diet modification.

  • Lung changes - Cough, trouble breathing if chest irradiated. Resolves over time.

  • Heart damage - Increased risks later in life. Stress test and heart scan monitoring.

Stem Cell Transplant

There are a few key reasons why an autologous stem cell transplant may be recommended for someone with Hodgkin lymphoma:

Salvage therapy if relapse occurs after initial chemotherapy ± radiation

  • High-dose chemo + transplant can potentially achieve a second remission when standard treatments have failed

Consolidation for high-risk disease

  • If lymphoma is refractory or responds poorly to initial chemo, transplant may be used to consolidate the response

Avoid late effects of prolonged chemo/radiation

  • Transplant allows shorter course of intensified therapy versus years of ongoing lower-dose treatment

Deliver higher chemotherapy doses

  • The transplant "rescues" bone marrow from doses higher than would be tolerable without stem cell support

Eliminate residual disease

  • The intensive chemo aims to fully eradicate any lingering lymphoma cells that may cause relapse

Here’s what typically takes place with stem transplants: 

Stem Cell Mobilization

  • Patient receives low-dose chemotherapy along with growth factor drug (G-CSF)

  • This mobilizes stem cells to move from bone marrow into circulating peripheral blood

  • Needed because the stem cells in the marrow will be destroyed by the high-dose chemo to come

Stem Cell Transplant

  • The patient's own frozen stem cells are thawed and reinfused intravenously

  • The stem cells migrate to the bone marrow space and begin regenerating normal blood and immune system cells

  • This rescues the body from the high-dose chemo's effects

Stem Cell Harvest

  • Patient's blood is run through an apheresis machine that filters out the mobilized stem cells

  • Target is to collect at least 2 million CD34+ stem cells per kg body weight

  • These cells are then frozen and stored for later use

Recovery Period

  • Hospitalization is required until blood counts recover to safe levels and the patient is clinically stable

  • Growth factor drugs speed white blood cell recovery

  • Transfusions provide red blood cells and platelets as needed

  • Anti-infectives prevent infections from low immunity

  • The transplanted stem cells continue maturing over weeks to months to fully reconstitute the marrow

High-Dose Chemotherapy

  • Intensive, systemic chemotherapy is given to maximize anti-cancer effect

  • Very high doses can be used because the frozen stem cells will "rescue" the patient afterwards

  • This chemo essentially wipes out all rapidly dividing cells like cancer as well as the bone marrow

Surgery

Surgery has a very limited role in Hodgkin lymphoma outside of diagnostic biopsies. Removal of the spleen, known as splenectomy, may rarely be done if the spleen is enlarged and diseased from lymphoma involvement. But chemotherapy and/or radiation are the standards of care.

Supportive Care

Supportive care is vital for managing Hodgkin lymphoma and treatment side effects. Services may include:

  • Growth factor drugs to counter low blood cell counts

  • Anti-nausea medications

  • Antibiotics for fevers and preventing infection

  • Transfusions for anemia

  • Appetite stimulants and nutritional support

  • Psychosocial counseling and assistance with day-to-day activities

Overview of typical survival rates for early and advanced stage classical Hodgkin lymphoma with modern chemotherapy and radiation treatment:

Early Stage (Stage I-II)

  • With combined chemo (ABVD) and involved-field radiation, the 5-year overall survival rate is 90-95%.

  • 10-year overall survival is also around 90%.

  • Overall cure rates exceed 85-90%.

So in summary, modern combined modality treatment with chemotherapy regimens like ABVD or BEACOPP along with selected radiation results in excellent 5- and 10-year survival exceeding 85-90% for early stage classical Hodgkin lymphoma. More advanced disease is somewhat harder to cure, but survival rates still approach 80% at 5 years with aggressive upfront treatment.

Advanced Stage (Stage III-IV)

  • With more intensive chemo (escalated BEACOPP) plus radiation to bulky disease, 5-year overall survival is around 80-90%.

  • 10-year overall survival is approximately 75%.

  • Cure rates are 70-80% for advanced disease with this approach.

  • Outcomes are worse if multiple relapses occur or disease is refractory to initial chemo.

Immune Checkpoint Inhibitors

Drugs like nivolumab (Opdivo) and pembrolizumab (Keytruda) are anti-PD-1 checkpoint inhibitors used for relapsed/refractory classical Hodgkin lymphoma. They block PD-1 on immune T-cells, which disables a pathway tumors use to evade immune detection. This boosts the immune response against Hodgkin cells.

These drugs are given intravenously every 2-3 weeks until disease progression or unacceptable toxicity. Fatigue, fever, nausea, rash, and diarrhea are common side effects. More severe autoimmune reactions affecting organs like lungs, colon, liver, kidneys, or endocrine glands can sometimes occur. Patients require close monitoring for these immune-related adverse events.

Monoclonal antibodies and immune checkpoint inhibitors offer newer immunotherapy options that harness the immune system against Hodgkin lymphoma. But balancing efficacy and unique toxicities requires careful patient selection, monitoring, and management.

overview of the effectiveness of these Hodgkin lymphoma immunotherapies in more natural language:

When used alone in Hodgkin lymphoma patients whose disease has come back after transplant or other treatments, the drug brentuximab vedotin can make the cancer go into full remission in about 3 or 4 out of every 10 patients treated. It also keeps the cancer from progressing for around 9 to 13 months on average.

Adding brentuximab to standard chemotherapy as initial treatment for advanced stage Hodgkin lymphoma helps about 7 to 12 out of every 100 patients stay progression-free for at least 2 years, compared to chemotherapy alone.

The antibody rituximab, when combined with chemotherapy and/or radiation, leads to a response in approximately 8 or 9 out of every 10 patients with nodular lymphocyte-predominant Hodgkin lymphoma.

For classical Hodgkin lymphoma that has returned after initial chemotherapy, the PD-1 checkpoint inhibitors nivolumab and pembrolizumab result in an overall response in around 65 to 70 out of every 100 patients. And the cancer disappears entirely in about 15 to 20 out of every 100 patients treated.

Early research also shows that combining a PD-1 drug with brentuximab might improve response compared to the PD-1 inhibitor alone.

So while not stand-alone cures, these newer immunotherapy options provide important additional ammunition against relapsed or treatment-resistant Hodgkin disease.

Developing Insights

As in so many areas of cancer research, there are new insights in breakthroughs that are being made frequently. Sometimes these new insights and approaches take years to make it to mainstream availability. Others offer us insight that can be used fairly quickly if the results of the research are well proved out. As an example of that, here's a summary of relatively recent research on how the cancer cells impact the immune system in cases of Hodgkin's lymphoma. This can potentially lead to changes in treatment in the near future.

Researchers from the Wellcome Sanger Institute conducted a comprehensive study on Hodgkin lymphoma, a type of blood cancer. Their findings offered fascinating insights into the disease's intricacies.

In Hodgkin lymphoma, cancer cells cleverly send signals to certain immune cells, such as macrophages, monocytes, and cDC2 dendritic cells, attracting them. Once these immune cells are near, the cancer cells instruct them not to attack. The study revealed that these immune cells surrounding the cancer cells even had molecules that suppressed their ability to fight tumors.

The researchers used advanced techniques to understand the interactions between cells in the immune microenvironment around Hodgkin lymphoma tumors. They employed single-cell sequencing and spatial transcriptomics, combined with microscope imaging data from biopsies. These methods allowed them to see which genes were active in each cell and how these cells were positioned relative to one another.

The study identified two distinct microenvironments around the cancer cells, which gave clues about the success of traditional treatments like chemotherapy. When there were high concentrations of immune cell clusters around the cancer cells, treatment was more likely to fail. On the other hand, a microenvironment with a high presence of stromal cells, which indicate past tissue repair, was associated with successful treatment. In such cases, the immune system might have already partially succeeded in fighting the disease, and additional treatment could help eradicate the cancer entirely.

Dr. Ben Stewart, the study's first author, highlighted how the combination of single-cell, spatial transcriptome, and histological data provided detailed insights into how Hodgkin lymphoma evades the immune response. The approach used in this study could serve as a roadmap for molecular pathology, applicable to other diseases as well.

Understanding how Hodgkin lymphoma tumors bypass the body's immune response opens new possibilities for treatment. Dr. Chris Carey, a senior author of the study, suggested that if patients with higher concentrations of immune cell clusters around the tumor could be identified, treatments could be tailored to them. In such cases, chemotherapy could be limited, and doctors could proceed directly to immune-based therapies with a better chance of success.

Furthermore, the cellular messaging used by cancer cells to manipulate immune cells presents a potential drug target. Disrupting this signaling could allow the immune system to respond as it should and attack the cancer cells.

Dr. Sam Behjati, a senior author of the study, emphasized how single-cell and spatial transcriptomic approaches are providing a new level of detail for studying human health and disease. When combined with other types of data, these techniques enable a highly specific understanding of what's happening in the human body, and this precision is essential for advancing the treatment of diseases like Hodgkin lymphoma.