Hodgkin’s lymphoma (lymphogranulomatosis) is a malignant disease of lymphatic system (lymph nodes), developing from the so-called Berezovsky-Reed-Sternberg cells and Hodgkin cells derived from B lymphocytes. The cause of the disease is unknown. As a rule, young people (20-40 years old) are affected; the disease is rare among children. The difference from other types of lymphoma is the presence of above-mentioned abnormal cells in biopsy specimen of the affected lymph node.
Hodgkin’s lymphoma accounts for about 6% of all malignant diseases among children. The disease can affect children of any age, but is extremely rare in the group under 5 years of age. Boys, according to statistics, get sick more often than girls. Despite the severity of situation in which young patients and their parents find themselves, there is a way out!
After all, the disease can be completely cured. The main thing is not to waste precious time, undergo modern and accurate diagnostics and get into the hands of real specialists. Israel is rightfully considered one of these places. Specialists at Pediatric Hematology Department at Tel Aviv Medical Clinic have achieved extraordinary success in treatment of all hematology oncology diseases in children, including lymphogranulomatosis.
An important feature of our department is a patient-oriented approach to diagnostic and treatment program. That is, doctors in their prescriptions are guided not only by template protocols, but also take into account the individual characteristics of each patient, his state of health and wishes regarding the diagnostic and treatment process.
An entire multidisciplinary team is involved in treatment of one patient. Department employs not only pediatric hematologists, but also oncologists, radiation therapists, chemotherapists, infectious disease specialists, rehabilitation specialists, immunologists, pediatricians, psychologists and other specialists whose help a sick child may need.
Causes and types of Hodgkin’s lymphoma
Unfortunately, the true causes of lymphogranulomatosis development are currently unknown. Under the influence of some factor, a genetic breakdown occurs in a certain population of blood B-lymphocytes, which give rise to malignant line of Berezovsky-Reed-Sternberg and Hodgkin’s cells. They, in turn, settle in the lymph nodes and cause lymphoma development.
Risk factors for lymphogranulomatosis:
- infection with Epstein-Barr virus (infectious mononucleosis in past);
- primary or secondary immunodeficiency conditions;
- a family history of lymphogranulomatosis (presence of this disease in relatives).
Depending on histological picture, there are 2 types of Hodgkin’s lymphoma (this is important to determine, since the selection of drugs to treat the disease depends on type):
Classic Hodgkin’s lymphoma is a variant of nodular sclerosis (70–80% of cases), a variant of mixed cellularity, lymphocytic depletion and enriched in lymphocytes. Most cases of classic variants are diagnosed in the early stages of process, most often the upper cervical lymph nodes are affected. There are often no general symptoms.
Non-classical Hodgkin’s lymphoma (nodular with a predominance of lymphocytes) is very rare, peripheral lymph nodes are affected, the course is slow and benign, as a rule, one group of lymph nodes is affected. It responds well to treatment, including relapses.
Symptoms of lymphogranulomatosis in children
You can suspect a disease in a child using the following signs:
- Nonspecific general symptoms are general weakness, loss of weight and appetite, prolonged fever for no apparent reason, itchy skin.
- Sustained enlargement of lymph nodes, when the causes of this phenomenon cannot be determined. Both peripheral lymph nodes can enlarge (in this case they can be noticed or palpated) and internal ones (such lymphadenopathy is most often discovered by chance during ultrasound of internal organs for other reasons).
- Symptoms associated with extranodal lesions of tumor process – enlargement of liver, spleen, changes in bones, bladder, skin.
- Symptoms associated with enlarged internal lymph nodes are cough, superior vena cava syndrome, breath shortness, flatulence, constipation, intestinal obstruction.
Clinical course of Hodgkin’s lymphoma is divided into 4 stages:
- lymph node or 1 anatomical group is affected, or there is 1 extranodal lesion without lymph node involvement.
- Pathological process affects 2 or more anatomical groups of lymph nodes on one side of diaphragm, or stage 1 or 2 for nodal lesions with limited spread of pathological process to adjacent extranodal organ.
- Affected lymph nodes on both sides of diaphragm or lymph nodes above diaphragm plus simultaneous involvement of spleen.
- Damage presence to a distant extranodal organ, plus any damage to lymph nodes.
Prognosis, as well as selected set of therapeutic measures, depends on stage at which the disease is detected. Therefore, a patient with suspected lymphogranulomatosis must be carefully examined so as not to miss a single affected lymph node or organ. Our specialists are helped in this by modern diagnostic equipment and the latest medical imaging techniques, which are actively used in TAMC Pediatric Hematology Clinic.
Modern diagnostics methods of Hodgkin’s lymphoma
Hodgkin’s lymphoma can be suspected based on symptoms described above, but to confirm the diagnosis, a biopsy of the affected lymph node or other organ and histological examination of obtained material is required. It is important to know that all biopsy specimen of our patients are sent for revision to the best pathohistological laboratories in Israel. Thanks to such checks, we are absolutely sure of diagnosis correctness and correctness of selected treatment regimen.
Specific histological findings in a tissue sample for lymphogranulomatosis are Berezovsky-Reed-Sternberg cells and Hodgkin cells, which allows the diagnosis to be verified with 100% accuracy. Immediately after histological examination, an immunohistochemical study of biopsy specimen is carried out, which makes it possible to distinguish between different types of receptors on the surface of malignant cells and, based on these data, to select the most effective treatment regimen.
Any invasive procedure, including biopsy, in children is performed according to world pediatric practice standards under sedation or general anesthesia so that young patients do not experience pain, fear or other psychological discomfort.
All patients must undergo a general blood test and other studies if necessary. Unfortunately, peripheral blood reacts to the disease only in 10-15% of patients; in the rest it remains unchanged, which does not allow diagnosing the disease during preventive examinations.
During trepan biopsy of bone marrow, changes are also observed relatively rarely – in 6% of patients, specific lymphoma cells can be seen in bone marrow puncture.
The next step after histological confirmation of the diagnosis is imaging studies, which make it possible to scan every square centimeter of the body and find all affected lymph nodes and extranodal foci or absence state of such. For this purpose, contrast-enhanced CT, contrast-enhanced MRI, PET-CT, and digital radiography are used.
Before starting a treatment program, functional studies of heart, lungs, and kidneys must be performed, since it is necessary to make sure that the function of these organs is not impaired.
If certain extranodal organs are affected, certain other tests may be required. For example, gastroscopy, thoracoscopy, laparoscopy, ultrasound of abdominal organs, kidneys, spinal puncture and cerebrospinal fluid tests, etc.
Prognosis for Hodgkin’s lymphoma in children
According to modern hematology clinics, 87% of patients diagnosed with lymphogranulomatosis live 5 years or more. 5-year survival rate depends on disease stage at which it was discovered. So, with stage 1, the 5-year survival rate is 94%, with stage 2 – 91%, 3 and 4 – 81%.
Thus, lymphogranulomatosis prognosis depends on the stage at which the disease is detected. One of treatment advantages at TAMC medical center is early and accurate diagnosis using modern diagnostic equipment, so our patients have excellent recovery rates and subsequent long life without relapses.
Modern treatment of lymphogranulomatosis
Developing a treatment plan for a small patient with lymphogranulomatosis, doctors of our medical center are guided by two basic principles. First: treatment is carried out taking into account only the world’s best treatment protocols, based on principles of evidence-based medicine. Second: all medical care is personalized, that is, specialist does not use a template of one treatment regimen for everyone, and procedures and drugs are selected individually, taking into account child’s age, state of health, stage of disease, parents’s wishes, data from histological, immunohistochemical studies, etc.
Chemotherapy
Chemotherapy is the main treatment for Hodgkin’s lymphoma. The essence of the technique is systemic application of drugs that have the ability to prevent the proliferation or completely destroy malignant cells. The main disadvantage of chemotherapy is that the drugs affect not only tumor cells, but also healthy cells in the body, leading to their destruction. This is precisely what causes the main side effects of chemotherapy. TAMC specialists use only proven and high-quality chemotherapy drugs from well-known global manufacturers.
Modern chemotherapy regimens for Hodgkin’s lymphoma in children are:
- BEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone.
- Stanford V: doxorubicin, vinblastine, chlormethine, vincristine, bleomycin, etoposide and prednisone.
- OEPA: vincristine, etoposide, prednisone and doxorubicin.
- COPDAC: cyclophosphamide, vincristine, prednisone and dacarbazine.
Children’s cancer centers are constantly looking for new, more effective and safer chemotherapy drugs, so treatment protocols will change and improve over time. Our doctors follow all news and recommendations in this area in order to quickly and effectively introduce innovations into practice.
Radiation therapy
In past, every course of treatment for lymphogranulomatosis included a course of radiation therapy, but with introduction of modern chemotherapy protocols and other biological drugs, not all patients need radiation therapy. It is used only in certain cases where the response to first-line treatment is incomplete.
There are 2 types of radiation therapy:
- Remote (this type used for lymphogranulomatosis) – when the source of radiation is outside the body. For this purpose, such devices as modern linear accelerators are used. The newer the device, the safer it is. Our patients have access only to high-quality and safe expert-class devices, so they can be confident in treatment course effectiveness and minimal side effects.
- Contact (brachytherapy) – when radioactive material is placed in a capsule and implanted directly into the tumor tissue. Thus, it is possible to minimize the negative impact of ionizing radiation on surrounding healthy cells, while achieving maximum therapeutic effect in neoplasm area. For lymphogranulomatosis, brachytherapy is almost never used.
Targeted therapy and immunotherapy
This type of immunotherapy (biological therapy) is used for some types of Hodgkin’s lymphoma. Drugs for targeted therapy have a targeted effect; they are “trained” to act on certain points of malignant cells, blocking their reproduction or functioning. As a result of this effect, the tumor cell quickly dies. A significant advantage of this class of drugs is their selectivity of action, that is, they do not affect healthy cells, unlike classical chemotherapy. Examples of drugs for targeted therapy are brentuximab, pembrolizumab.
Immunotherapy for lymphomas has several types. In addition to targeted drugs, there are various monoclonal antibodies, immune checkpoint inhibitors, CAR-T cell therapy, and small molecule inhibitors.
CAR-T cell therapy is the latest innovation in fight against hematological cancers, including lymphomas. To produce such a medicine, you need modern genetic engineering laboratory and highly qualified personnel. CAR-T cells are produced individually for each patient. To do this, a blood sample is first taken from the patient, from which T cells are separated. These white blood cells are then genetically modified to display chimeric antigen receptors (CARs) on their surface, matching the type of tumor cells found in the same patient. Next, such “upgraded” cells are multiplied by cloning and returned back to patient’s blood, where they actively “hunt down” malignant cells and destroy them.
Hematopoietic stem cell transplantation
Bone marrow transplantation, or hematopoietic stem cell transplantation, is a modern method of treating hematology oncology diseases. It is not a mainstay treatment for Hodgkin’s lymphoma, but may be used if there is no response to first-line therapy.
Transplantation can be autologous, when patient is the donor before the start of entire treatment course, and allogeneic, when donor is a relative or any other person who meets certain criteria.
Hematopoietic stem cell transplantation procedure is complicated and requires application of modern equipment and qualified doctors with experience in this field of medicine, so you should trust only trusted specialists and medical institutions. One of them is Pediatric Hematology Oncology department of Tel Aviv Medical Clinic.
