Lymphomas (lymphogranulomatosis and non-Hodgkin's lymphomas)

Lymphoma is a cancer that affects lymphocytes (cells of the immune system). In some cases, it may be called cancer of the lymphatic system, but this is a misnomer, since cancer refers to tumors originating from epithelial tissues, and the term lymphoma is used for malignant neoplasms of the lymphatic system. There are many types of lymphoma, and their treatment depends on the type of disease, stage, response to previous therapy, if any, the patient's age and general health. That is, the approach can range from simple observation to high-dose chemotherapy and hematopoietic stem cell transplantation.

Types of lymphomas

All lymphomas are divided into two large groups - Hodgkin and non-Hodgkin. Hodgkin's lymphomas are characterized by the presence of special Berezovsky-Sternberg cells in the tumor tissue. Non-Hodgkin's lymphomas are a very heterogeneous group of tumors that are also divided into two large subgroups - T-cell and B-cell.

Based on the nature of their course, non-Hodgkin lymphomas are divided into the following types:

• Benign lymphomas, or indolent. They progress very slowly, but are very difficult to radically cure.
• Aggressive lymphomas. In this case, the disease inevitably progresses and, if left untreated, leads to the death of the patient. For such lymphomas, chemotherapy is mandatory.
• Super-aggressive forms. With such tumors, in the absence of treatment, the disease progresses very quickly and malignant cells spread almost like lightning throughout the body. Death may occur within several months or even weeks after the development of the disease. To defeat the disease, radical measures are needed, for example, high-dose chemotherapy with stem cell transplantation.

In children

If you compare the symptoms of lymphoma in adults and children, it turns out that aggressive forms are more common in younger organisms. Such diseases are quite common among young patients - they account for up to 10% of all types of cancer they encounter. They are usually diagnosed between the ages of five and ten years; in other groups it is much less common.

The situation is complicated by the fact that young children cannot describe their condition to doctors in detail, so they have to determine the disease by typical signs. If a child sweats a lot, gets tired quickly and becomes irritable (or apathetic), this is a serious reason to contact a specialist.

Symptoms of lymphoma

Signs of lymphoma can be very diverse, but they can all be combined into three large groups:

• Lymphadenopathy, or enlarged lymph nodes. Quite often there are situations where the first symptoms of lymphoma are painless enlargement of the lymph nodes. In this case, the patient consults a doctor and the diagnosis is established quite quickly. However, there are cases when lymphadenopathy affects internal lymph nodes that are not accessible to palpation or inspection. They can only be detected using ultrasound, CT or MRI and then this sign may not be detected.
• B-symptoms are a triad of symptoms that are the most specific sign of lymphoma. These include night sweats (sweating can be very severe, to the point that the patient wakes up on a pillow wet with sweat), unexplained weight loss and fever not associated with an infectious disease.
• Symptoms that develop when lymphoma spreads beyond the lymphatic system and spreads to internal organs. If the central nervous system is involved, this may include headaches, vomiting, and changes in vision. If the lungs are involved - cough, shortness of breath. Thus, the symptoms will depend on which organs or systems are affected.

Diagnostics

If, after a thorough examination, the pediatrician finds signs of Hodgkin's lymphoma, then he gives a referral to a specialized hospital (clinic of pediatric oncology and hematology).

The following are carried out in the hospital:

• Examination of the affected tissue . The main method of diagnosing lymphoma is a biopsy (surgical removal of the affected lymph node or tissue and examination of the material under a microscope). Based on the results of examining a tissue sample, it is possible to accurately determine whether a child has Hodgkin lymphoma, and if so, what type of lymphoma.
• Analysis of the prevalence of disease in the body. After making a diagnosis, it is necessary to find out how far the disease has spread throughout the body and what organs it has affected. For this purpose, PET-CT with glucose is performed. According to indications, a bone marrow examination is performed (trephine biopsy of the bone marrow in patients with stages IB, IIB-IV), osteoscintigraphy, and MRI for bone lesions.
• If there is a history of cardiovascular pathology, a heart murmur is listened to, and LVEF (left ventricular ejection function) is performed.

Rice. 3. Damage to the intrathoracic lymph nodes in Hodgkin lymphoma

Methods for diagnosing lymphoma

There are no screening tests to diagnose lymphoma. Typically, the diagnosis is established based on the results of an examination that the doctor prescribes for the patient after he has presented with complaints of symptoms of a “viral infection.”

Blood tests and lymph node biopsy (carried out in different ways: using a needle, removing the entire lymph node or part of it) help to establish the correct diagnosis. In some cases, a red bone marrow biopsy is required.

Lesions can be detected using CT, MRI, ultrasound, and positron emission tomography (PET).

Diagnosis of non-Hodgkin's lymphomas

Diagnosis of NHL includes a number of laboratory and instrumental research methods. However, the primary thing is to examine the patient with the collection of complaints, assessment of his general condition, clarification of hereditary history and the presence of chronic or other tumor diseases. All groups of peripheral lymph nodes are palpated and their size, elasticity, mobility, and pain are assessed, as well as palpation examination of the liver and spleen. The condition of the palatine tonsils and nasopharynx is assessed.

A number of laboratory research methods are prescribed:

• general blood test with leukocyte count and platelet count determination;
• biochemical blood test with assessment of liver function (bilirubin, total protein, albumin) and kidney function (urea, creatinine), determination of electrolyte levels (K, Na, Ca), lactate dehydrogenase levels, uric acid;
• coagulogram;
• diuresis measurement and urinalysis;
• determination of markers of viral infections: Epstein-Barr virus, HIV, hepatitis;
• determination of serum immunoglobulins.

Instrumental diagnostic methods are performed:

• Ultrasound of lymph nodes, abdominal and pelvic organs.
• X-ray of the chest organs. Allows you to establish enlargement of the thymus, mediastinal lymph nodes, and identify lesions in the lungs.
• CT to assess the condition of the chest, abdominal and pelvic organs, neck.
• MRI for symptoms of damage to the central nervous system and spinal cord.
• Osteostincigraphy and radiography of bones in the presence of bone pain.
• Endoscopic examination of the stomach with biopsy and determination of Helicobacter pylori infection.

In all cases, to verify the diagnosis, it is mandatory to perform a biopsy of tumor tissue for histological examination and determination of the immunophenotype of the tumor.

To determine the involvement of the bone marrow in the tumor process, a bone marrow biopsy and myelogram are performed.

Treatment of Hodgkin's lymphoma in Moscow and Krasnodar

For Hodgkin's lymphoma in the early stages, treatment is carried out according to the ABVD regimen. This is a combination of chemotherapy drugs:

• adriamycin (doxorubicin),
• bleomycin,
• vinblastine
• dacarbazine.

All of them are administered using a dropper. Each course takes 4 weeks. The patient may require 4–6 courses, meaning treatment for lymphoma will last 4–6 months.

Chemotherapy according to the ABCD regimen leads to immunodeficiency and susceptibility to infections, fatigue, weakness, multiple bruises, skin reactions (redness, darkening, etc.), hair loss, infertility, sensitivity to light, etc. In addition to chemotherapy, patients with Hodgkin lymphoma must radiation therapy is needed.

The prognosis in the early stages is good; many people manage to go into long-term remission, that is, essentially recover. Only a doctor who takes into account the patient’s age, hemoglobin levels, lymphocytes, albumin, etc. can give a more accurate forecast.

At stages III–IV (they are called late), a different chemotherapy regimen is needed. It's called BEACOPP . These are bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone. Some of these drugs are taken in the form of capsules and tablets, while others are administered through a dropper.

Side effects from BEACOPP are quite common for chemotherapy: decreased immunity, fatigue, weakness, shortness of breath, hair loss, multiple bruises, nosebleeds, infertility, etc. One course lasts 3 weeks, the patient may need up to 8 courses, which will take a total of six months . Radiation therapy in this case is not always necessary - it is carried out only if the full effect of chemotherapy has not been achieved and there are residual formations. The prognosis for stage III–IV Hodgkin lymphoma depends on the same factors as in the early stages.

Unfortunately, due to the toxicity of the drugs used, the consequences of treatment (malignant neoplasms, heart disease, etc.) may appear years later.

According to statistics, the disease can return in 10-15 percent of patients who initially had Hodgkin lymphoma in the early stages, and in 20-40 percent in the later stages. Also, 10–15 percent of patients will be resistant to first-line chemotherapy (the one given first). In all these cases, second-line chemotherapy is quite effective. It can be different:

• GEM-P (gemcitabine, cisplatin, methylprednisolone);
• GDP (gemcitabine, dexamethasone, cisplatin);
• GVD (gemcitabine, vinorelbine, pegylated liposomal doxorubicin);
• IGEV (ifosfamide, mesna, gemcitabine, vinorelbine, prednisolone);
• mini-BEAM (carmustine, etoposide, cytarabine, melphalan);
• ESHAP (etoposide, steroid, cytarabine, cisplatin);
• ICE (ifosfamide, carboplatin, etoposide);
• DHAP (dexamethasone, cytarabine, cisplatin).

Unfortunately, until now there have not been enough studies to answer the question: which of these treatment regimens is most effective. Usually two courses of this chemotherapy are sufficient, but some patients require longer treatment.

If the lymphoma is localized, that is, the affected area is limited, then radiation therapy is also performed.

After this course of treatment, the patient undergoes high-dose chemotherapy and autologous transplantation of hematopoietic stem cells (pre-selected own bone marrow cells, from which all blood cells are formed). After this, 40–60 percent go into remission. The chances are higher for those who have had a good response to second-line therapy.

If a relapse occurs after transplantation of your own cells, then there are two options:

A) palliative care, that is, improving the quality of life, but not leading to recovery;

B) high-dose chemotherapy and transplantation of hematopoietic stem cells from a donor.

In the West, some monoclonal antibodies are also used (for example, brentuximab vedotin). However, these drugs are not registered in Russia. The choice in favor of one or another type of treatment is made depending on the general condition of the person and the aggressiveness of the disease.

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Stages of non-Hodgkin's lymphomas

The clinical stage of lymphoma is determined based on a set of diagnostic studies performed before prescribing treatment.

Each stage is divided into substages depending on the presence of common symptoms:

Substage A is characterized by the absence of general symptoms, substage B is characterized by their presence.

Also, stages 1-3 may be characterized by:

• E – localized extranodal lesion.
• S – damage to the spleen.

Pregnancy and Hodgkin's lymphoma

Of course, during treatment for Hodgkin's lymphoma, a woman should take precautions to avoid becoming pregnant. However, if the disease was diagnosed when she was already expecting a child, then the decision on further treatment is made based on the severity of her condition. If lymphoma is found during the first trimester, then it is better to postpone treatment at least until the second or third, since chemotherapy is quite toxic, and in the first trimester it can have a particularly bad effect on the development of the fetus and cause various defects. In the future, at 32–36 weeks, labor can be induced to begin treatment faster.

If the disease right now threatens the health and life of the mother, then combination chemotherapy ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) is used in any trimester. As a last resort, radiation therapy is used, but only above the diaphragm. What risks does such treatment pose to a child in the second and third trimesters? Low weight, intrauterine growth restriction, premature birth, stillbirth, mental retardation and learning disabilities. Steroids may be used along with chemotherapy to reduce the toxicity of the drugs and speed up the development of the baby's lungs, making premature birth less dangerous.

If Hodgkin's lymphoma recurred during pregnancy and was not discovered for the first time, then it is better to have an abortion, and then undergo high-dose chemotherapy and hematopoietic stem cell transplantation.

Non-Hodgkin's lymphoma

Non-Hodgkin's lymphomas can be divided into three groups: indolent, aggressive and highly aggressive.

Indolent lymphomas

Indolent lymphomas progress slowly, and it is almost impossible to cure them completely: they constantly recur. The World Health Organization classifies the following diseases as indolent lymphomas:

• lymphocytic lymphoma;
• lymphoplasmacytic lymphoma (Waldenström macroglobulinemia);
• plasma cell myeloma (plasmocytoma);
• hairy cell leukemia;
• follicular lymphoma (stages I and II);
• B-cell marginal zone lymphoma;
• lymphoma from mantle cells (such lymphoma can be aggressive);
• T-cell leukemia of large granular lymphocytes;
• mycosis fungoides;
• T-cell prolymphocytic leukemia;
• NK cell leukemia of large granular lymphocytes.

If the doctor did a biopsy (took a tissue sample) of the lymph node and found that the lymphoma is indolent, then the lymph node is simply removed, and the patient periodically comes to the hematologist, talks about his symptoms, if any, undergoes an examination and takes tests. This tactic is called “watch and wait.”

Quite often, without treatment, a person may not feel sick for a long time (months or even years). Therefore, therapy is delayed until symptoms appear that impair quality of life.

Starting chemotherapy right away does not make much sense, since it will not increase life expectancy, but one line of therapy will already be used, and doctors have a limited number of them at their disposal. Therefore, for example, if indolent lymphoma is diagnosed during pregnancy, treatment can usually be delayed until after delivery.

When a person with indolent lymphoma goes into remission, they may be given the drug rituximab as maintenance therapy so they are more likely to relapse later.

Aggressive and highly aggressive lymphomas

Aggressive lymphomas are:

• follicular lymphoma (stage III);
• diffuse large B-cell lymphoma;
• lymphoma from mantle cells;
• peripheral T-cell lymphoma;
• anaplastic large cell lymphoma.

Highly aggressive lymphomas:

• Burkitt's lymphoma;
• B-lymphoblastic leukemia/lymphoma and B-cell precursors;
• T-cell leukemia/lymphoma;
• T-lymphoblastic leukemia/lymphoma from T-cell precursors.

If the lymphoma is aggressive or highly aggressive, it is best to start chemotherapy right away, even if the patient is pregnant. The treatment regimen for such lymphomas is approximately the same: first, several courses of chemotherapy are given, often with rituximab, and remission is achieved. Rituximab (MabThera) is a drug that came out in the late 1990s and has greatly improved survival in lymphomas. It belongs to a group of substances called monoclonal antibodies. They are made up of immune cells that recognize cancer cells, attach to them and block their growth or kill them.

Radiation therapy for aggressive lymphomas can be used if the affected area is limited. Then combination treatment gives better results than chemotherapy alone.

It is impossible to say how many people will avoid relapse, even if we talk about one type of lymphoma. Only a doctor can give a prognosis, having calculated everything taking into account the characteristics of a particular patient.

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If remission ultimately cannot be achieved or if a relapse occurs, then second-line chemotherapy is used - with those drugs that have not yet been used, then high-dose chemotherapy and autologous transplantation of hematopoietic stem cells, that is, restoration of bone marrow killed by drugs using pre-saved own cells. As such, autologous transplantation does not have a curative function. It is needed only so that a person’s hematopoiesis is restored and he survives after such therapy. If after this the disease returns, then high-dose chemotherapy is carried out followed by an allogeneic transplantation of hematopoietic stem cells from a donor. The donor can be a brother or sister, if there is tissue compatibility with them, or a suitable person from the database of potential donors. Such transplantation also plays a therapeutic role. Hematopoietic stem cells form the human bone marrow, which ensures the functioning of the immune system. In other words, after such a transplantation, the patient’s immunity is no longer his own, but from the donor. And new lymphocytes destroy residual tumor cells. But at the same time, cells arising from donor hematopoietic stem cells can attack other organs of the patient - this graft-versus-host reaction is deadly. The doctor must recognize it as quickly as possible and begin treatment with hormones or cyclosporine, that is, immunosuppressive therapy - suppressing the immune system. Transplantation of donor hematopoietic stem cells is a last resort, as the mortality rate from such treatment is 30 percent.

If a relapse occurs after such a transplantation or if for some reason it cannot be carried out (for example, due to the person’s severe physical condition or old age - over 65 years old), then the patient receives maintenance treatment - tablet chemotherapy. These are standard cytostatics (drugs that block the division of tumor cells) in a small dose. It is also very important that the person receives palliative care: lymphoma in this situation can worsen the quality of life, so doctors fight the symptoms. For example, with pain, nausea, loss of appetite, shortness of breath, etc.

Active treatment for lymphoma may stop earlier, even after first-line therapy. This happens if, due to treatment, a person has a stroke, heart attack or other complication. Over time, some patients find it harder and harder to endure chemotherapy, the person recovers longer than necessary, and the lymphoma grows without treatment in time. Then the person is prescribed maintenance chemotherapy, which will not cure the disease, but will somewhat inhibit the growth of tumor cells.

Even before treatment, you need to discuss possible infertility with your doctor, since chemotherapy drugs can deprive a woman of the opportunity to become pregnant and a man to become the biological father of his child. Therefore, it is generally recommended that women freeze their eggs and men freeze their sperm. However, in Russia, women will have problems with this, since reproductive specialists usually have no experience in caring for patients with lymphoma, and they do not undertake to carry out hormonal stimulation of superovulation, which is necessary before retrieving a large number of eggs.

If, after treatment for lymphoma, you are in remission, the doctor will want to see you once every few months, then less and less often, as the likelihood of relapse decreases over time.

Diffuse large B-cell lymphoma

This aggressive type of lymphoma is the most common among non-Hodgkin lymphomas. If the disease is detected early, most patients are better off with a shortened course of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). Radiation therapy is also necessary, but if it has the potential to worsen the quality of life in the future, it is better to do without it. If large cell lymphoma affects the testicle, epidural space (outside the dura mater of the spinal cord), or paranasal sinuses, the risk of damage to the central nervous system increases. Therefore, in such cases, it is necessary to carry out intrathecal chemotherapy, that is, inject the drug into the cerebrospinal fluid. Also, if the lymphoma has touched the testicle, it is necessary to remove it and irradiate this and the adjacent area.

In case of relapse or if the lymphoma is resistant to first-line therapy, it is recommended to use the GDP regimen (gemcitabine, dexamethasone, cisplatin). An alternative may be ICE (ifosfamide, carboplatin, etoposide) or DHAP (dexamethasone, high dose cytarabine, cisplatin). In all these cases, rituximab should also be added if it was not used the first time. This is followed by first high-dose chemotherapy and then autologous hematopoietic stem cell transplantation (BMT). If the disease returns after this, then the only option is allogeneic hematopoietic stem cell transplantation, that is, from a donor.

If for some reason TCM cannot be performed or a person does not respond to second-line therapy, then all he can do is fight the symptoms.

Peripheral T-cell lymphoma

This group of predominantly aggressive lymphomas is treated according to the standard regimen: first, combination chemotherapy is carried out - most often according to the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone). If the patient is under 60 years of age, then etoposide is added to these drugs. Sometimes radiation therapy is also performed. If a relapse occurs later and the person responds to second-line chemotherapy, he may be eligible for a hematopoietic stem cell transplant. However, in the case of peripheral T-cell lymphoma, this approach is less likely to produce good results. If treatment for lymphoma does not help, the doctor will most likely prescribe supportive care, and palliative care will also be needed in the future.

Brain lymphoma in Israel: treatment prices

An important aspect of treatment for brain lymphoma in Israel is cost. Top Assuta Clinic sets prices for treatment in such a way that they are as affordable as possible for foreign patients. Compared to other countries on the medical tourism map, Israel sets prices 30-40% lower than clinics in the US and Germany. This is due to generous government funding and a large influx of patients.

By ordering a call from our employee, you have the opportunity to receive a calculation of the planned treatment completely free of charge. To do this, you just need to leave a request on our website!

Positive aspects of treatment for brain lymphoma in Israel

• Level of professionalism. The clinic employs international-level professionals, professors and doctors of medical sciences.
• Treatment methods. Israeli doctors are developing highly effective treatment methods for a speedy recovery of the patient.
• Diagnostics. Top Assuta uses the latest technical equipment, which is not available in many other countries. All research performed is truthful and accurate.
• Attitude towards patients. The clinic takes care of the patient’s comfortable stay within its walls. All Top Assuta employees try to meet the patient halfway in resolving all issues that arise, including everyday ones.
• Prices. Israeli clinics set the most affordable prices in comparison with other medical tourism countries.
• Another important positive aspect of treatment for brain lymphoma in Israel is reviews. Patients treated at Top Assuta leave a large number of positive reviews about the clinic. This once again confirms the high level of services provided by the clinic.

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(15 votes, average: 4.9 out of 5)

Treatment of follicular lymphoma

If the disease is detected at stages I–II, then such lymphoma is classified as indolent and, if necessary, is treated with radiation therapy. But the likelihood of the disease returning is extremely high.

If follicular lymphoma was first diagnosed at stage III–IV, it is recommended to be treated with rituximab in combination with chemotherapy. For example, according to the regimen R-CVP (rituximab, cyclophosphamide, vincristine and prednisone), R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) or BR (bendamustine and rituximab). In some cases, the doctor may prescribe long-term use of rituximab after complex treatment.

But if, despite sensitivity to chemotherapy, a rapid relapse occurs, then a person who is able to withstand high-dose chemotherapy undergoes autologous hematopoietic stem cell transplantation. If this does not help, they resort to donor cell transplantation.

The prognosis for follicular lymphoma is determined by the special FLIPI index (Follicular Lymphoma International Prognostic Index). Risk factors such as the patient’s age over 60 years, elevated LDH levels, late stage of the disease (III–IV), decreased hemoglobin levels less than 120 g/l, and more than 5 areas of nodal lesions are taken into account. For each risk factor, 1 point is added. The survival prognosis depends on the score.

Burkitt's lymphoma

After removing a lymph node containing tumor cells, a person with Burkitt's lymphoma must undergo 4-6 courses of chemotherapy to prevent progression of the disease and early relapse (up to a year). Treatment regimens commonly used are CODOX-M (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate) combined with IVAC (ifosfamide, cytarabine, etoposide, and methotrexate injected into the cerebrospinal fluid). Injecting the drug into the cerebrospinal fluid (intrathecal chemotherapy) is very important because Burkitt's lymphoma is fraught with complications in the central nervous system.

The CALGB 9251 protocol is also sometimes used. This is a highly toxic combination chemotherapy that causes a person to end up in the hospital for a long time. If the body cannot withstand such aggressive treatment for Burkitt's lymphoma, then the EPOCH regimen (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) with rituximab is used.

During treatment of Burkitt's lymphoma, tumor disintegration (lysis) syndrome often develops. This is a dangerous condition in which, due to the destruction of tumor cells, various substances enter the blood in large volumes, causing metabolic disorders and leading to kidney failure. To prevent this syndrome from occurring, you need constant monitoring by a competent specialist, active fluid infusion through a vein, as well as constant correction of electrolytic imbalance.

If Burkitt's lymphoma returns or is resistant to treatment, there are no treatment options other than clinical trials - the person is given palliative care to improve their quality of life.

Treatment of lymphoplasmacytic lymphoma

Lymphoplasmacytic lymphoma is an uncommon type of B-cell non-Hodgkin lymphoma. It got its name because, under a microscope, its cells resemble both lymphocytes and plasma cells. Most often it occurs in people over 60 years of age, it grows slowly, but sometimes there is rapid aggressive growth. For many patients, doctors adhere to active surveillance tactics. If signs of rapid growth appear, chemotherapy drugs in combination with prednisone and dexamethasone, targeted drugs, and immunotherapy are prescribed. In rare cases, for extranodal lesions, radiation therapy is used.

Causes

The exact causes of lymphoma have not yet been established - however, this is the case with many malignant tumors. But we can say that there are factors contributing to the development of the disease.

These factors include previous viral diseases, bacterial infections, use of immunosuppressants, the influence of certain chemicals, as well as certain age and gender.

People over 55 years of age are at risk, since the immunity of such patients is weakened due to natural causes and accumulated diseases. But lymphomas are quite common, so they are also found in younger groups - up to 35 years old, in childhood. Gender dependence is noted in the case of Hodgkin lymphoma - it is more common in men.

Dangerous viruses that can subsequently lead to such a disease include the Epstein-Barr virus, mononucleosis, hepatitis, HIV, certain types of herpes, etc.

When we talk about the chemical factor, we mean regular contact with aggressive chemicals that have a toxic effect. Here, people who regularly come into contact with various solvents, pesticides and similar dangerous components are at risk.

As for immunosuppressants, we are usually talking about situations where a person is diagnosed with an autoimmune disease. In this case, you need to suppress the body's reaction to its own cells - as a result, the lymphatic system may also suffer. This occurs in systemic lupus erythematosus, rheumatoid arthritis, etc.