Hodgkin's lymphoma (lymphogranulomatosis) in children

Childhood Hodgkin lymphoma (HL, Hodgkin's disease, lymphogranulomatosis, Hodgkin lymphoma, HL) is a malignant tumor of lymphoid tissue with a specific granulomatous histological structure. It is a rare monoclonal lymphoid neoplasm characterized by the following four features: HL usually manifests itself in children, usually arises in the cervical lymph nodes, includes scattered large mononuclear Hodgkin cells and multinucleated Reed-Sternberg cells in a background of non-neoplastic tumors. Inflammatory cells and characteristic neoplastic cells are often surrounded by T lymphocytes. Hodgkin lymphoma usually has a favorable prognosis, although this depends on several factors. [ 1 ]

Epidemiology

The disease occurs in all age groups, except for children in their first year of life; it is rare in children under 5 years of age. Hodgkin's disease accounts for about 40% of all lymphomas in children. In the age group under 12 years, boys are more often affected; in adolescents, the ratio of affected boys and girls is approximately equal. According to International Registers, the incidence of lymphogranulomatosis in children is 0.7-0.9 cases per 100,000 children. The risk of developing Hodgkin's lymphoma is higher in children with primary immunodeficiency (ataxia-telangiectasia, agamma globulinemia), rheumatoid arthritis and systemic lupus erythematosus. There are no accurate statistics on the incidence of lymphogranulomatosis in Ukraine.

The disease accounts for 11% of all lymphomas seen in the United States. It has a bimodal distribution, with most affected patients being between 20 and 40 years of age, and another peak at 55 years of age and older. It affects boys more (85% of cases) than girls, especially in the pediatric population. Nodular sclerosis Hodgkin lymphoma is more common in young adults, while mixed cellularity Hodgkin lymphoma tends to affect older adults. The prevalence of the subtypes of classical Hodgkin lymphoma is as follows: nodular sclerosis, classical Hodgkin lymphoma (70%), mixed cellularity classical HL (25%), lymphocyte-rich classical Hodgkin lymphoma (5%), and lymphocyte-depleted classical HL (less than 1%).

Causes Hodgkin's lymphoma in a child

The causes of Hodgkin's lymphoma (lymphogranulomatosis) are unknown. The role of the Epstein-Barr virus, detected in tumor cells in lymphogranulomatosis (most often in the mixed-cell variant in children of a younger age group), is discussed. A hypothesis of the pathogenesis of Hodgkin's lymphoma is proposed, according to which the uncontrolled proliferation of tumor cells formed in the lymph node as a result of mutation of germ cell B-lymphocytes is based on a block of programmed death, apoptosis.

The tumor substrate of Hodgkin's lymphoma is giant Berezovsky-Reed-Sternberg cells, their number in the tumor does not exceed 1-10%. In 90% of cases, these cells originate from relatively mature slowly proliferating B-cells of the germinal centers of the lymph nodes, in other cases they are descendants of T-lymphocytes (possibly cytotoxic) or natural killers. Berezovsky-Sternberg cells are capable of producing cytokines, which causes the formation of a specific granulomatous histological structure of the tumor and the development of characteristic clinical manifestations of the disease.

[ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ]

Risk factors

There is an increased risk of Hodgkin lymphoma with autoimmune disease infection and immunosuppression. There is also evidence of a familial predisposition in Hodgkin lymphoma. Epstein-Barr infection has been found to be more common in the mixed cellularity and lymphocyte-depleted subtypes of Hodgkin lymphoma. Loss of immune surveillance has been suggested as a possible etiology of EBV-positive disease. No other virus has been found to play an important role in the pathogenesis of the disease. Immunosuppression caused by solid organ or hematopoietic cell transplantation, immunosuppressant therapy, and human immunodeficiency virus (HIV) infection have a higher risk of developing Hodgkin lymphoma. Patients with HIV usually have a more advanced stage, unusual lymph nodes, and a poor prognosis. Studies have shown that there is a tenfold increase in HL in same-sex siblings of patients with Hodgkin lymphoma, suggesting a role for gene-environment interactions in susceptibility to Hodgkin lymphoma.[ 8 ], [ 9 ], [ 10 ]

Pathogenesis

Hodgkin lymphoma has unique neoplastic cells of both classical and NLP-HL types. The Reed-Sternberg (RS) cell is a neoplastic large multinucleated cell with two mirror-image nuclei (owl eyes) on a reactive cellular background. The RS cell is pathognomonic for classical HL. RS cells are derived from germinal center B cells with IgH variable region segment mutations. RS secrete cytokines to recruit reactive cells that include IL-5 and transforming growth factor-beta (TGF-beta). The RS cell is usually aneuploid without consistent cytogenetic abnormality. Clonal Ig gene rearrangements have been detected in most isolated RS cells. Immunohistochemical stains for RS cells are positive for CD30, CD15 but usually negative for CD20 and CD45, which are positive only in NLP-HL neoplastic cells. In addition to CD15 and CD30, RS cells are typically positive for PAX5, CD25, HLA-DR, ICAM-1, Fascin, CD95 (apo-1/fas), TRAF1, CD40, and CD86. There are variants of RS cells that include Hodgkin cells, mummified cells, and lacunar cells. Hodgkin cells are variants of mononuclear RS cells.

Mummified cells exhibit condensed cytoplasm and pyknotic, reddish nuclei with indistinct chromatin. Lacunar cells have multilobulated nuclei, small nucleoli, and abundant pale cytoplasm that is often retracted during tissue fixation and dissection, leaving the nucleus in what appears to be an empty space (lacunar space).

On the other hand, NLP-HL lacks typical RS cells but has lymphocytic and histiocytic cells that are characterized by larger cells with rolled-up multilobed nuclei (also known as "popcorn cells" or LP cells). LP cells show a nucleus with multiple nucleoli that are basophilic and smaller than those seen in RS cells. LP cells show clonally rearranged immunoglobulin genes that are found only in isolated single LP cells. LP cells are typically positive for C020, CD45, EMA, CD79a, CD75, BCL6, BOB.1, OCT2, and J chain.

Histopathology

Morphology is used to distinguish variants of Hodgkin lymphoma and NLP-HL. Nodular sclerosis HL shows a partial nodular growth pattern with fibrous bands and an inflammatory background. RS cells are rare. However, lacunar cells are more common. Mixed cellularity HL shows a diffuse or vaguely nodular growth pattern without sclerotic bands in an inflammatory background. Subtle interstitial fibrosis may be present, and the classic diagnostic Reed-Sternberg cells are often seen.

Lymphocyte-rich HL typically shows a nodular growth pattern on an inflammatory background that is composed predominantly of lymphocytes, with rare or absent eosinophils or neutrophils. RS cells and Hodgkin mononuclear cells are usually present. Lymphocyte-depleted HL has a diffuse hypocellular growth pattern with increased areas of fibrosis, necrosis, and unusual inflammatory cells. RS cells are usually present. NLPHL is characterized by an overall nodular architecture with LP cells in a background of small B lymphocytes, follicular dendritic cells, and follicular T lymphocytes. In conclusion, the morphology and immunophenotype of both the neoplastic cells and the background infiltrate are critical for the diagnosis of HL and its various subtypes.

Symptoms Hodgkin's lymphoma in a child

The main symptom of Hodgkin's lymphoma in children is enlarged lymph nodes (lymphadenopathy).

Among extranodular localizations, it is necessary to note (up to a quarter of cases) damage to the spleen, often the pleura and lungs are involved in the process. Damage to any organs is possible - bones, skin, liver, bone marrow. Very rarely, tumor growth into the spinal cord, specific infiltration of the kidneys and thyroid gland are observed.

[ 11 ], [ 12 ], [ 13 ], [ 14 ]

Lymphadenopathy

The lymph nodes are painless, dense and mobile, often arranged in conglomerates, there are no signs of inflammation. The enlargement of the lymph nodes occurs gradually and asymmetrically. In 90% of cases, the supradiaphragmatic groups of lymph nodes initially enlarge, in 60-80% - the cervical, in 60% - the mediastinal. The supra- and subclavian, axillary, as well as the intra-abdominal and inguinal lymph nodes may be enlarged.

The following features are characteristic of mediastinal localization:

• the lymph nodes of the anterior and middle mediastinum are affected, rarely the thymus;
• the course of the disease may be asymptomatic for a long time;
• with a significant increase, characteristic symptoms gradually develop - obsessive unproductive cough, superior vena cava syndrome (dilation of the veins of the neck, face), hoarseness, dysphagia, dyspnea;
• possible growth into the pleura, lungs, trachea, esophagus with the development of corresponding symptoms (pleurisy develops more often, pericarditis occasionally).

Splenomegaly

The spleen often enlarges with lymphogranulomatosis, but not always due to tumor damage (when the organ is removed, lesions are detected in only 26% of cases). Almost always, damage to the lymph nodes of the splenic hilum and paraaortic nodes is detected. Symptoms of hypersplenism do not develop even with pronounced splenomegaly.

Lung damage in lymphogranulomatosis

The following features are characteristic of lung damage in lymphogranulomatosis:

• the lymph nodes of the mediastinum and/or the root of the lung are not affected;
• the localization and type of damage vary - peribronchial, in the form of widespread foci, sometimes with decay;
• thickening of the pleura with the presence of effusion.

Accurate diagnosis is only possible with the help of MRI.

Central nervous system damage

CNS involvement may develop in advanced cases of Hodgkin's lymphoma, most often as a result of spread from the paravertebral lymph nodes along nerve pathways and vessels into the spinal canal and intracranially, or as a result of dissemination.

The symptoms are caused by the tumor compressing the brain tissue with the development of paresis and paralysis, the appearance of pain, convulsions, and increased intracranial pressure.

Bone and bone marrow damage

Bones are rarely affected by lymphogranulomatosis; more often the process is localized in the vertebrae and hip joints.

Bone marrow is involved in the pathological process in 5-10% of cases. The lesion is diagnosed when foci of lymphogranulomatous tissue with single Hodgkin and Berezovsky-Sternberg cells are detected during histological examination of bone marrow obtained by trepanobiopsy. Cells specific to Hodgkin lymphoma are almost never detected in aspiration material. Bone marrow lesion, along with the frequent phenomenon of hemophagocytosis, can be the cause of cytopenia.

Hodgkin's lymphoma is often accompanied by thrombocytopenic purpura with a typical clinical picture. Coombs-positive hemolytic anemia is observed, which at the beginning of the disease can complicate the verification of the diagnosis.

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Biological activity syndrome

An important and pathognomonic symptom of Hodgkin's lymphoma is the complex of biological activity caused by the production of cytokines:

• intermittent fever (with a rise in body temperature above 38 °C), not associated with infection, not relieved by adequate anti-infective therapy;
• profuse night sweats;
• weight loss (when determining the stage, weight loss of more than 10% over the previous 6 months is taken into account).

There may also be other symptoms (itching, weakness, anorexia) that are not taken into account during staging.

Stages

A staging system is a way for a cancer doctor to summarize how far the cancer has spread. The Hodgkin lymphoma staging system is the Lugano classification, based on the older Ann Arbor system. It consists of 4 stages, labeled I, II, III, and IV.

The staging system for Hodgkin lymphoma is based on the location of lymphadenopathy, the number and size of lymph nodes, and whether extranodal lymph node involvement is systemic. The commonly used staging system divides the disease into four stages:

• Stage I: damage to individual areas of the lymph nodes or lymphoid structure.
• Stage II: involvement of 2 or more lymph node areas on one side of the diaphragm; the number of anatomical areas should be indicated in the suffix (e.g., II2) + involvement of one or more lymph node groups on the same side of the diaphragm (II E). The number of lymph node groups involved may be indicated in the staging definition
• Stage III: involvement of lymph nodes or structures on both sides of the diaphragm.
  • III1: with or without splenic, hilar, celiac, or portal nodes
  • III2: with para-aortic, iliac or mesenteric nodes
• Stage IV: Involvement of extranodal sites other than those designated E (E: single extranodal site, or adjacent or proximal to a known nodal site of disease). Diffuse or disseminated involvement of one or more non-lymphoid organs or tissues, with or without lymph node involvement. Liver and bone marrow involvement always denotes stage IV

Each stage may also be assigned a letter (A or B). B is added (e.g. stage IIIB) if the person has any of these B symptoms:

1. Loss of more than 10% of body weight over the previous 6 months (without dieting).
2. Unexplained temperature not 38° C.
3. Profuse night sweats.

If a person has any B symptoms, it usually means the lymphoma is progressing, and more intensive treatment is often recommended. If there are no B symptoms, the letter A is added to the stage.

Determining the stage without using invasive methods is staging. Clarification of the tumor spread using surgical intervention (laparotomy with splenectomy, liver and intra-abdominal lymph node biopsy, trephine biopsy) is surgical staging (in this case, the stage is classified as pathological). With modern visualization capabilities, surgical staging is used less and less often, especially since there is a risk of complications of laparotomy with splenectomy, such as the development of fulminant sepsis (at any time after surgery), intestinal obstruction, adhesive disease. To prevent sepsis before splenectomy, patients must be vaccinated against pneumococcus and Haemophilus influenzae.

Indications for the use of a particular staging method are determined depending on the therapeutic programs used in the clinic. If the basis of treatment is radiation therapy, it is necessary to determine the localization of the lesion as accurately as possible using surgical staging. Surgical intervention may be required to obtain material in complex diagnostic situations.

Resistant or relapsed Hodgkin lymphoma

Resistant or relapsed HL is not part of the formal staging system, but doctors may use these terms to describe what happens with lymphoma in some cases.

The terms "resistant" or "progressive disease" are used when the lymphoma does not go away or progresses (grows) during treatment. Recurrent disease means that the Hodgkin lymphoma went away after treatment but comes back after a while. When lymphoma comes back, it may be in the same place where it started or in another part of the body. It may happen soon after treatment or years later.

Forms

Different types of Hodgkin lymphoma can develop, progress, and spread differently, and they may be treated differently.

Classical Hodgkin's lymphoma

Classical Hodgkin lymphoma (cHL) accounts for more than 9 out of 10 cases of Hodgkin lymphoma in developed countries.

The cancer cells in cHL are called Reed-Sternberg cells. These cells are usually an abnormal type of B lymphocyte. The enlarged lymph nodes in people with cHL usually have a small number of Reed-Sternberg cells and many normal immune cells around them. These abnormal immune cells cause the lymph nodes to enlarge.

Classic Hodgkin lymphoma has 4 subtypes:

1. Nodular sclerosis or NSCHL: This is the most common type of Hodgkin's disease in developed countries, accounting for about 7 out of 10 cases. It is most common in adolescents and young adults, but can occur in people of any age. It usually begins in the lymph nodes in the neck or chest.
2. Mixed cell lymphoma or MCCHL: This is the second most common type, found in about 4 out of 10 cases. It is mostly seen in people with HIV infection. It also occurs in children and older adults. It can start in any lymph node, but most often occurs in the upper half of the body.
3. Hodgkin lymphoma with lymphocyte predominance: This subtype is rare. It usually begins in the upper half of the body and rarely occurs in more than a few lymph nodes.
4. Lymphocytic Hodgkin lymphoma or lymphocyte depletion: This is a rare form of Hodgkin's disease. It is seen mainly in older people and people with HIV infection. It is more aggressive than other types of HL. The lymph nodes most commonly affected are those in the abdomen (belly), as well as the spleen, liver, and bone marrow.

Nodular lymphocyte-predominant Hodgkin's lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for about 5% of cases. The cancer cells in NLPHL are large cells called popcorn cells (because they look like popcorn), which are variants of Reed-Sternberg cells. You may also hear these cells referred to as lymphocytic and histiocytic (L&H) cells.

NLPHL usually begins in the lymph nodes in the neck and armpits. It can begin in people of any age and is more common in men than women. This type of HL tends to progress slowly and is treated differently than the classic types.

Complications and consequences

Cardiovascular diseases (pericarditis, heart defects and ischemic heart disease) from radiation therapy.

Additionally, drugs such as anthracyclines can cause cardiomyopathy.

Lung disease can result from medications such as bleomycin and radiation therapy.

Secondary cancer is a common cause of morbidity and mortality. The most common secondary malignancy after treatment in patients with Hodgkin lymphoma is lung cancer.

Myelodysplastic syndrome/acute myeloid leukemia is also a major concern following alkylation therapy.

Other cancers that may develop include sarcoma of the breast, soft tissue, pancreas, and thyroid.

Infectious complications do occur, but they can be treated with empirical antibiotic therapy.

Finally, patients may develop depression, peripheral neuropathy, family problems, and sexual dysfunction.

Diagnostics Hodgkin's lymphoma in a child

The definitive diagnosis of Hodgkin lymphoma is made by biopsy of the lymph node or suspected organ. It is important to note that fine needle aspiration or core biopsy often shows nonspecific results due to a low proportion of malignant cells and loss of architectural information. Therefore, excisional biopsy should be performed if suspicion of Hodgkin lymphoma is high. To establish a definitive diagnosis, the biopsy specimen must identify the RS cell or LP cell. Further testing is necessary to determine the stage at which treatment should be performed and to provide prognostic information.

Laboratory diagnostics of Hodgkin's lymphoma

Clinical blood analysis reveals moderate neutrophilia and lymphopenia, and almost all patients have an increased ESR. Moderate eosinophilia and thrombocytosis are possible (these changes have no direct diagnostic value).

There are no specific changes in the biochemical blood test. The activity of lactate dehydrogenase is not increased or is increased by no more than 2 times compared to normal values (a greater increase in activity is possible with hemolysis). An increase in the concentration of ferritin, ceruloplasmin and fibrinogen has no diagnostic value, but in some clinics these indicators are taken into account as prognostic factors.

Specific changes in biochemical parameters (increased levels of direct and indirect bilirubin) are possible in rare initial liver lesions, in cholestasis due to compression by a tumor, and also in hemolytic anemia.

Immunological studies reveal quantitative and qualitative disturbances of the T-cell link of immunity both during disease progression and in remission. These changes may persist for many years after recovery. Lymphopenia, a decrease in the number of circulating T-helpers, and a decrease in the ability of lymphocytes to mitogen-stimulated blast transformation are typical. In patients with Hodgkin's lymphoma, suppression of skin tests for tuberculin may complicate the diagnosis of tuberculosis. These indicators are not important for the diagnosis of the disease, but the state of immunodeficiency must be taken into account when monitoring individuals who have had lymphogranulomatosis.

To assess bone marrow damage in Hodgkin's lymphoma, performing a puncture aspiration biopsy is almost always uninformative. A mandatory element of the examination is a trephine biopsy from four points (except for stages IA and IIA of the disease).

Instrumental diagnostics of Hodgkin's lymphoma

Diagnostic laparotomy is currently used extremely rarely, only in exceptional cases when obtaining a tumor substrate is impossible in any other way. During the procedure, the abdominal cavity is inspected to detect possible damage. A biopsy of accessible lymph node groups enlarged by more than 1.5 cm, and a marginal biopsy of both liver lobes are required. Splenectomy is not recommended.

Chest X-ray, chest/abdomen/pelvis CT scan, and PET/CT scan can help with diagnosis. PET/CT scan has now become the standard test for assessing response to treatment in HL and most lymphomas. Overall, a comprehensive workup is necessary for both diagnosis and staging of Hodgkin lymphoma.

Radiographic examination methods are necessary not so much to confirm the diagnosis of lymphogranulomatosis, but to clarify the localization of lesions, their prevalence, i.e. to determine the stage of the disease and the volume of necessary antitumor therapy.

Chest X-ray is the most accessible, mandatory and quite informative method of examination when lymphoma is suspected. Images are taken in two projections (direct and lateral), which allows to detect enlargement of the mediastinal lymph nodes, infiltrates in the lungs, their size and location, the degree of displacement of the chest organs, the presence of effusion in the pleural cavity and in the pericardial cavity.

Ultrasound examination of the abdominal cavity and lymph nodes provides information on the enlargement of lymph nodes and the presence of infiltrates in parenchymatous organs. The method is used as a first-line diagnostic study and for dynamic monitoring to assess treatment results or remission status.

CT of the chest, abdominal cavity, and pelvic cavity is a highly informative non-invasive method that allows verifying the presence and nature of the lesion, especially when using contrast. However, when using CT, the spleen and liver gates, mesenteric and iliac lymph nodes are not clearly visualized. In children under 3 years of age, CT may be difficult to perform for technical reasons (need for anesthesia).

MRI is used to detect bone and CNS lesions.

Radioisotope diagnostics are useful for confirming the presence of bone lesions (study with technetium preparations) and monitoring the state of remission by accumulation of the radiopharmaceutical in the mediastinal lymph nodes (study with gallium preparations).

Differential diagnosis

In the cervical form of lymphogranulomatosis, vulgar and tuberculous lymphadenitis are excluded. In such cases, foci of chronic infection are often found in the oral cavity (periodontitis, chronic tonsillitis, etc.), nasopharynx (adenoiditis, etc.), paranasal sinuses. Symptoms of intoxication, inflammatory changes in the blood, and softening of the lymph node in the center can be palpated. In addition, Brill-Simmers disease, infectious mononucleosis, and leukemia are also considered. In case of mediastinal lesions, it is necessary to differentiate from tuberculosis, sarcoidosis, thymus tumors, non-Hodgkin's lymphomas, and dermoid cysts. In case of intra-abdominal lesions, differential diagnosis is made with tuberculous mesadenitis, pseudotuberculosis, non-Hodgkin's lymphomas, and in case of hepatosplenomegaly - with storage diseases, portal hypertension, chronic hepatitis, liver cirrhosis, tumors.

Treatment Hodgkin's lymphoma in a child

Treatment of Hodgkin lymphoma depends largely on the histologic characteristics, stage of the disease, and the presence or absence of prognostic factors. The goal of treatment for patients with Hodgkin lymphoma is to cure the disease while controlling short-term and long-term complications.

Hodgkin lymphoma is a systemic disease that is best treated by an interprofessional team to achieve the best outcomes.

Treatment for Hodgkin lymphoma is primarily provided by oncologists. However, a patient may first see a primary care physician or nurse practitioner with symptoms suggestive of lymphoma. The key is prompt referral to a specialist so that treatment can begin.

Treatment of Hodgkin lymphoma depends largely on the histologic characteristics, stage of the disease, and the presence or absence of prognostic factors. The goal of treatment for patients with Hodgkin lymphoma is to cure the disease while controlling short-term and long-term complications.

The pharmacist should educate the patient about the medications, their benefits, and side effect profile. Additionally, the pharmacist should ensure that the patient has completed the recommended preoperative testing before dispensing the medications. The oncology nurse should monitor the patient for acute side effects of chemotherapy drugs and educate the patient on how to minimize complications. [ 16 ]

Since many patients develop anxiety and depression, they should be consulted by a psychiatrist.

A dietitian should educate the patient about what to eat and what to avoid.

Numerous treatment programs for Hodgkin's lymphoma have been developed in various countries. Their main elements are radiation therapy and polychemotherapy using a relatively narrow range of drugs. It is possible to use only radiotherapy, only chemotherapy, or a combination of both methods. Radiotherapy and chemotherapy programs for lymphogranulomatosis are constantly being improved: their effectiveness increases, immediate and late toxicity decreases without the development of resistance. The treatment tactics for Hodgkin's lymphoma are determined by the stage of the disease and the patient's age. [ 17 ]

Treatment for Hodgkin lymphoma in children is slightly different than treatment for adults. For adults, the main goal of treatment for Hodgkin lymphoma in children is to cure the lymphoma. Doctors adjust treatment based on the child's age, the extent of the lymphoma, how well the lymphoma responds to treatment, and other factors. [ 18 ]

If a child has already reached puberty and the muscles and bones are fully developed, treatment is usually the same as for adults. But if the child has not reached their full size, chemotherapy (chemotherapy) will likely be preferred over radiation therapy. This is because radiation can affect bone and muscle growth and prevent children from reaching their normal size.

Children's bodies usually tolerate chemotherapy better in the short term than adults. But some side effects are more common in children. Because some of these side effects can be long-term, and because of late effects, childhood cancer survivors need careful attention for the rest of their lives.

Most children with cancer in the United States are treated at a center that is part of a Children's Oncology Group (COG). All of these centers are affiliated with a university or children's hospital.

At these centers, doctors treating children with Hodgkin lymphoma often use treatment plans that are part of clinical trials. The goal of these studies is to find the best treatments that cause the fewest side effects.

Treatment of classical Hodgkin's lymphoma in children

When treating children with classical Hodgkin lymphoma, doctors often combine chemotherapy (chemotherapy) with low-dose radiation. Chemotherapy often involves combinations of many drugs, not just the usual ABVD regimen for adults, especially for cancers that have unfavorable features or are at a more advanced stage. This approach has excellent success rates, even for children with more advanced disease.

• Stages IA and IIA, favorable

Treatment usually begins with chemotherapy alone, at the lowest dose that can be curative. A PET scan may be used to see if the treatment is working and/or if there is any lymphoma in the body. If the HL does not clear up completely, radiation therapy or additional chemotherapy may be needed.

Research has shown that HL in children can be treated without the use of radiation. This avoids the long-term problems that may arise. However, when radiation therapy is used, the dose and area treated are kept as small as possible. If radiation is applied to the lower body in girls and young women, the ovaries must be protected to preserve fertility.

• Stages I and II, unfavorable

Treatment will likely consist of more intensive chemotherapy combined with radiation therapy, but the dose and field of radiation will still be minimal.

• Stages III and IV

Treatment involves more intensive chemotherapy, either alone or combined with low-dose radiation therapy, to areas with extensive disease (areas with a lot of lymphoma).

Treatment of relapsed or refractory Hodgkin lymphoma

If the lymphoma comes back or is no longer treatable, various chemotherapy regimens may be tried. Other options may include a stem cell transplant or treatment with immunotherapy drugs (sometimes along with chemotherapy).

Treatment of nodular lymphocyte-predominant Hodgkin's lymphoma in children

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is very rare in children. There is no single effective treatment, and the treatments used are often very similar to those used to treat cHL and/or those used to treat NLPHL in adults.

There is one exception: In early-stage NLPHL in children, surgery to remove the affected lymph node may be the only treatment needed. After surgery, these children are closely monitored for signs of lymphoma. Chemotherapy may be used if it recurs.

The polychemotherapy regimens MOPP (mustargen, vincristine, procarbazine and prednisolone) and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) proposed in the 1970s are basic in many protocols for the treatment of lymphogranulomatosis. They are used as the first line of therapy in an alternating regimen with varying frequency, depending on the stage, with or without radiation. According to the Stanford University Children's Hospital (USA), the 5-year relapse-free survival (RFS) with such tactics is 95%. The same principle is used by the French working group on the treatment of Hodgkin's disease. Due to the high oncogenicity of mustargen, in modern protocols it is replaced by cyclophosphamide (COPP course), etoposide, ifosfamide, lomustine, cytarabine, platinum drugs are included in polychemotherapy courses. For the treatment of resistant forms of lymphogranulomatosis, immunotherapy and hematopoietic stem cell transplantation (mainly autologous) are increasingly used. [ 19 ]

Hematopoietic stem cell transplantation is performed in refractory or relapsed patients.

The results of Hodgkin's lymphoma treatment in domestic clinics before the 1990s cannot be correctly assessed due to the lack of a unified definition of staging and the methods of therapy used. Over the past decade, most children's specialized clinics have been using the lymphogranulomatosis treatment protocol developed by German pediatric oncohematologists. This protocol has shown high efficiency with low toxicity of HD-DAL-90: event-free survival for 10 years was 81%, overall survival was 94%.

All patients with Hodgkin lymphoma require long-term follow-up, which includes:

• Annual medical examination.
• Management of cardiac risk factors.
• Vaccination of patients with splenectomy.
• Stress test or echocardiogram.
• Carotid ultrasound.
• TSH, blood biochemistry and complete blood count.
• Measurement of lipid and glucose levels.
• Mammography in women.
• Low-dose chest CT to detect lung lesions.

[ 20 ], [ 21 ], [ 22 ], [ 23 ], [ 24 ], [ 25 ], [ 26 ]

Prevention

Some of the known risk factors for Hodgkin lymphoma (HL) can be modified (smoking or being overweight), so most cases of the disease cannot currently be prevented.

Being infected with HIV, the virus that causes AIDS, is known to increase your risk, so one way to limit your risk is to avoid known HIV risk factors, such as intravenous drug use or unprotected sex with unknown sexual partners.

Another risk factor for HL is infection with the Epstein-Barr virus (the cause of infectious mononucleosis, or mono), but there is no known way to prevent this infection.

Forecast

Hodgkin's disease in children has a different prognosis, which depends primarily on the stage at which treatment is started. In local forms of lymphogranulomatosis (IA, IIA), complete recovery is possible in 70-80% of children, although complete remission is achieved in 90%. Recovery can only be discussed 10 years after the completion of a successful course of primary treatment. Most relapses occur in the first 3-4 years after the end of therapy. The 5-year overall survival rate at stage 1 or 2a is approximately 90%; on the other hand, the 5-year survival rate for stage 4 disease is approximately 60%.

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