Where non-Hodgkin's lymphoma occurs most often Stages of non-Hodgkin's lymphomas and Hodgkin's lymphomas1

, monoclonal antibodies), radiation therapy and hematopoietic stem cell transplantation.

The modern WHO classification of lymphomas, adopted in 2008, largely abandoned the outdated opposition of “Hodgkin's lymphoma” and “non-Hodgkin's lymphoma”. Instead, the WHO classification has grouped more than 80 different forms of lymphomas into four main groups. In comparison, the previous classification of lymphomas, adopted in 1982 by the Working Group on Lymphoma and now obsolete, but still used for statistical comparison with previous decades, recognized and distinguished only 16 subtypes of non-Hodgkin's lymphoma.

The total (average) five-year survival rate for all types of NHL in the United States today is 69%. However, in fact, the five-year survival rates are very different for different types of NHL, different stages of the disease with the same form of NHL, as well as in different prognostic groups (determined by the presence of clinical and biological risk factors: a specific morphological subtype, immunophenotype, specific cytogenetic abnormalities, proliferative index of the tumor) within the same form of NHL.

Encyclopedic YouTube

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✪ A case of successful treatment of highly aggressive non-Hodgkin diffuse B large cell lymphoma

✪ Lymphoma - not a Sentence - Ranok - Inter

✪ Therapy for aggressive B-cell lymphomas. Alekseev S.M.

✪ Recurrent and resistant forms of Hodgkin's lymphoma. Modern view of the state of the problem

Subtitles

Causes of lymphomas

Different forms of lymphomas have different causes. For some forms, certain connections have been established with various etiopathogenetic factors (not necessarily the direct cause of the development of lymphoma in each case).

Infectious agents

Exposure to carcinogens and mutagens

Certain chemical carcinogens and mutagens, such as polychlorinated biphenyls (PCV), diphenylhydantoin (phenytoin), dioxin, and some phenoxy herbicides, contribute to the development of lymphomas.

Also, the development of lymphomas is facilitated by the use of cytostatic chemotherapy drugs, especially alkylating drugs, exposure to ionizing radiation, including medical radiation therapy.

Immunosuppression

The development of lymphomas, like other types of malignant neoplasms, is facilitated by the intake of immunosuppressants, in particular glucocorticoids, cyclosporine.

Genetic diseases

Genetic diseases such as Klinefelter's syndrome, Chédiak-Higashi syndrome, and ataxia-telangiectasia syndrome predispose to the development of lymphomas.

Autoimmune diseases

The predisposition to the development of lymphomas is also created by such autoimmune diseases as Sjogren's syndrome, trophic ulcers, rheumatoid arthritis, and systemic lupus erythematosus.

Epidemiology

The number of cases of non-Hodgkin's lymphoma worldwide has increased in recent decades. For example, in 2010, the world recorded 210,000 deaths from all forms of NHL, compared with 143,000 deaths from the NHL in 1990.

Historical background

Lymphogranulomatosis (LHM, LHR), or Hodgkin's disease, Hodgkin's lymphoma (HL) or Hodgkin's disease) was first isolated and described as a separate form of lymphoma by Thomas Hodgkin in 1832, and therefore named after his name. Hodgkin's lymphoma was historically the first form of lymphoma to be separately classified and characterized. Other forms of lymphoma have been identified and described later. In this regard, it became necessary to classify them. And since Hodgkin's lymphoma turned out to be much more sensitive to ionizing radiation than other forms of lymphomas, and had a more favorable prognosis compared to other lymphomas with the only treatment available at that time - radiation therapy, the isolation and classification of Hodgkin's lymphoma separately from other types of lymphomas had clinical importance for oncologists and their patients. The same situation - a more favorable prognosis compared to other types of lymphomas - continued to take place with the appearance of the first chemotherapy drugs - for example, mustine (substance) was used for a long time in the MOPP regimen for the treatment of lymphogranulomatosis. This explains why the enthusiasm of lymphoma researchers was initially almost entirely focused on Hodgkin's lymphoma (lymphogranulomatosis). The first generally accepted classification of Hodgkin's lymphoma was proposed by Robert J. Luke in 1963.

While there was a rapid consensus on the classification of Hodgkin's lymphoma, a large cohort of very different progression and prognosis lymphomas remained unclassified, contrasted with Hodgkin's lymphoma and informally referred to as "non-Hodgkin's lymphomas." The first generally accepted classification of non-Hodgkin lymphomas was the Rappaport classification proposed by Henry Rappaport in the first edition in 1956 and revised by him in 1966. Based on the development and improvement of Rappaport's classification, the Working Group on the Study of Lymphomas published a new classification of lymphomas in 1982. It officially introduced the term “non-Hodgkin's lymphomas” and defined three large groups of non-Hodgkin's lymphomas in accordance with the gradation of their clinical aggressiveness (the rate of cell proliferation and, accordingly, the rate of disease progression).

However, according to this classification, the NHL group consists of 16 completely different subspecies of "non-Hodgkin's lymphomas", which actually have little in common with each other, both clinically and biologically. They are grouped into three large groups according to the degree of their aggressiveness, but each subgroup contains tumors that have a completely different biological nature, different pathogenesis and a different prognosis, and require different approaches to treatment. However, the classification of NHL according to the degree of their aggressiveness is convenient in a practical sense. In less aggressive forms of NHL, long-term survival without treatment is possible, only on dynamic observation, while in more aggressive forms of lymphoma, the absence of active treatment can quickly lead to death. Therefore, without further clarification of the diagnosis, the name of the disease "non-Hodgkin's lymphoma" carries zero information content for both patients and doctors.

Modern use of the term

Despite all the difficulties and limitations, the classification of the Working Group on the Study of Lymphomas from 1982, and, accordingly, the broad diagnostic category and the term NHL ("non-Hodgkin's lymphomas") continue to be used for the collection and processing of statistics by many large agencies for the study of malignant tumors, cancer and lymphomas. So, in particular, the term NHL continues to be used in their statistics by IARC, the Canadian Society for the Study of Cancer, the American National Institute for the Study of Cancer.

Non-Hodgkin's lymphomas and HIV

Since 1987, the American Centers for Disease Control and Prevention (CDC) has included certain types of non-Hodgkin's lymphoma in the list of AIDS-associated tumors (that is, tumors characteristic of AIDS and, according to the definition of the term AIDS, a symptom of a patient with AIDS , and not just the carrier of HIV infection). It is believed that the immunosuppression observed in AIDS plays a role in the pathogenesis of AIDS-associated lymphomas, rather than HIV infection itself. Indeed, there is a clear correlation between the degree of immunosuppression (the number of CD4 + T cells and the ratio of CD4 + / CD8 +) and the risk of developing AIDS-associated forms of NHL. In addition, it is possible that other retroviruses, such as human T-cell leukemia virus (HTLV), are spread by the same mechanisms at both the cellular and population-epidemiological levels as HIV infection. This increases both the incidence of co-infection and the rate at which both types of retroviruses multiply if both enter the same organism. The natural course of HIV infection has changed significantly, and the frequency and rate of the transition from HIV to clinically apparent AIDS has decreased significantly in recent years due to the advent of highly active antiretroviral therapy (HAART). As a result, in recent years, the incidence of NHL in HIV-infected patients has significantly decreased.

see also

• Chemotherapy is one of the main treatments for lymphomas in general and NHL in particular
• CHOP is one of the most common chemotherapy regimens for NHL

Links

1. Monarch Disease Ontology release 2018-06-29sonu - 2018-06-29 - 2018.
2. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. - Oxford Univ Pr, 2008 .-- ISBN 978-92-832-2431-0.
3. SEER Stat Fact Sheets: Non-Hodgkin Lymphoma (unspecified) . NCI... Date of treatment June 18, 2014.
4. Maeda E, Akahane M, Kiryu S, Kato N, Yoshikawa T, Hayashi N, Aoki S, Minami M, Uozaki H, Fukayama M, Ohtomo K (2009). “Spectrum of Epstein-Barr virus-related diseases: A pictorial review”. Japanese Journal of Radiology. 27 (1): 4-19. DOI: 10.1007 / s11604-008-0291-2. PMID.
5. Peveling-Oberhag J, Arcaini L, Hansmann ML, Zeuzem S (2013). “Hepatitis C-associated B-cell non-Hodgkin lymphomas. Epidemiology, molecular signature and clinical management ”. Journal of Hepatology. 59 (1): 169-177. DOI: 10.1016 / j.jhep.2013.03.018. PMID.
6. Pinzone MR, Fiorica F, Di Rosa M, Malaguarnera G, Malaguarnera L, Cacopardo B, Zanghì G, Nunnari G (October 2012). “Non-AIDS-defining cancers among HIV-infected people”. Eur Rev Med Pharmacol Sci. 16 (10): 1377-88. PMID.
7. Kramer S, Hikel SM, Adams K, Hinds D, Moon K (2012). “Current Status of the Epidemiologic Evidence Linking Polychlorinated Biphenyls and Non-Hodgkin Lymphoma, and the Role of Immune Dysregulation”. Environmental Health Perspectives. 120 (8): 1067-75. DOI: 10.1289 / ehp.1104652. PMC. PMID.
8. Zani C, Toninelli G, Filisetti B, Donato F (2013). “Polychlorinated biphenyls and cancer: an epidemiological assessment”. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 31 (2): 99-144.

Malignant diseases of the lymphatic system or lymphomas: Hodgkin's and non-Hodgkin's are manifested by enlarged lymph nodes.

Non-Hodgkin's lymphomas unite a group of cancers that differ from the structure of their cells. Distinguish multiple non-Hodgkin's lymphomas by looking at the affected lymphoid tissue. The disease forms in the lymph nodes and organs with lymphatic tissue. For example, in the thymus gland (thymus), spleen, tonsils, lymphatic plaques of the small intestine.

Malignant cells

Lymphoma occurs at any age, but more often in the elderly. Non-Hodgkin's, most often occurs after 5 years of age. They tend to leave the site of primary development and invade other organs and tissues, for example, the central nervous system, liver, and bone marrow.

In children and adolescents, tumors of high malignancy are called "highly malignant NHL" because they cause new severe diseases in the organs and can be fatal. Low-grade, slow-growing non-Hodgkin lymphoma is more common in adults.

Causes of non-Hodgkin lymphomas

The causes of lymphomas are still being investigated by doctors. It is known that non-Hodgkin's lymphoma begins from the moment of mutation (malignant change) of lymphocytes. At the same time, the genetics of the cell changes, but its reason for its change has not been clarified. It is known that not all children with such changes get sick.

It is believed that the cause of the development of non-Hodgkin's lymphoma in children is the combination of several risk factors at once:

• congenital disease of the immune system (Wiskott-Aldrich or Louis-Bar syndrome);
• acquired immunodeficiency (eg, HIV infection);
• suppression of one's own immunity during organ transplantation;
• viral disease;
• radiation;
• certain chemicals and medicines.

Symptoms and signs of non-Hodgkin lymphoma

Symptoms of non-Hodgkin's lymphoma of an aggressive course and high malignancy due to the growth rate are manifested by a noticeable tumor or enlarged lymph nodes. They do not hurt, but they swell on the head, in the area or. It is possible that the disease begins in the peritoneum or chest, where it is impossible to see or feel the nodes. From here it spreads to non-lymphoid organs: the meninges, bone marrow, spleen, or liver.

Non-Hodgkin's lymphoma manifests itself:

• high fever;
• weight loss;
• increased sweating at night;
• weakness and fatigue;
• high fever;
• lack of appetite;
• painful well-being.

Shows non-Hodgkin's lymphoma symptoms of a specific type.

The patient may be suffering from:

• Abdominal pain, indigestion (diarrhea or constipation), vomiting and loss of appetite. Symptoms appear when the LN or abdominal organs (spleen or liver) are affected.
• Chronic cough, shortness of breath with damage to the lymph nodes in the cavity of the sternum, thymus and / or lungs, respiratory tract.
• Joint pain with damage to the bones.
• Headaches, visual disturbances, vomiting on a lean stomach, paralysis of the cranial nerves with damage to the central nervous system.
• Frequent infections with a decrease in the level of healthy white blood cells (with anemia).
• Pinpoint cutaneous hemorrhages (petechiae) due to low platelet count.

Attention! The symptoms of non-Hodgkin's lymphomas intensify over two to three weeks or more. In each patient, they manifest themselves in different ways. If one or 2-3 symptoms are noticed, then these can be infectious and diseases not associated with lymphoma. To clarify the diagnosis, you need to contact a specialist.

Stages of lymphoma

For lymphoblastic lymphoma, a classification (St. Jude Classification) has been proposed.

It includes the following categories:

1. Stage I - with a single lesion: extranodal or nodal of one anatomical region. The mediastinum and abdominal cavity are excluded.
2. Stage II - with a single extranodal lesion and involvement of regional LNs, primary lesion of the gastrointestinal tract (ileocyclic region ± mesenteric LN).
3. Stage III - with damage to the nodal or lymphoid structures on both sides of the diaphragm and primary mediastinal (including the thymus gland) or pleural foci (III-1). Stage III-2, independently of other foci, refers to any extensive primary intra-abdominal unresectable lesions, all primary paraspinal or epidural tumors.
4. Stage IV - with all primary lesions of the central nervous system and bone marrow.

For fungal mycosis, a separate classification has been proposed.

It provides:

1. Stage I, indicating changes in the skin only;
2. II - A stage with indication of skin lesions and reactively enlarged LN;
3. Stage III with LN with increased volume and verified lesions;
4. Stage IV with visceral lesions.

Forms of non-Hodgkin lymphomas

The form of NHL depends on the type of cancer cells under a microscope and on the molecular genetic characteristics.

The WHO international classification distinguishes three large groups of NHL:

1. B-cell and T-cell lymphoblastic lymphomas (T-LBL, pB-LBL), growing from immature progenitor cells of B-lymphocytes and T-lymphocytes (lymphoblasts). The group is 30-35%.
2. Mature B-cell NHL and mature B-form-ALL (B-ALL), growing from mature B-lymphocytes. These NHLs are among the most common forms of oncology - almost 50%.
3. Anaplastic large cell lymphomas (ALCL), accounting for 10-15% of all NHL.

Each major form of NHL has subspecies, but other forms of NHL are also less common.

Classification of Non-Hodgkin's Lymphomas (WHO, 2008)

Non-Hodgkin's includes:

B-cell lymphomas:

• B-cell precursor lymphomas;
• B-lymphoblastic lymphoma / leukemia;
• Mature B cell lymphomas;
• Chronic lymphocytic leukemia / small cell lymphocytic lymphoma;
• B-cell prolymphocytic leukemia;
• Lymphoma from cells of the marginal zone of the spleen;
• Hairy cell leukemia;
• Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia;
• Heavy chain diseases;
• Plasma cell myeloma;
• Solitary plasmacytoma of bones;
• Extraosseous plasmacytoma;
• Extranodal lymphoma from cells of the marginal zone of lymphoid tissues associated with mucous membranes (MALT lymphoma);
• Nodal lymphoma from cells of the marginal zone;
• Follicular non-Hodgkin's lymphoma;
• Primary cutaneous centrofollicular lymphoma;
• Lymphoma from cells of the mantle zone;
• , non-specific;
• Large B-cell non-Hodgkin's lymphoma with a large number of T cells / histiocytes;
• Lymphatic granulomatosis;
• Non-Hodgkin's lymphoma diffuse large B-cell lymphoma associated with chronic inflammation;
• Primary cutaneous large B-cell lymphoma;
• Intravascular large B cell lymphoma
• ALK-positive large B-cell lymphoma;
• Plasmablastic lymphoma
• Large B-cell lymphoma derived from HHV8-associated multicentric Castleman disease
• EBV positive large B cell lymphoma of the elderly
• Primary mediastinal lymphoma (thymic) large B-cell;
• Primary exudative lymphoma
• B-cell lymphoma with a morphology intermediate between diffuse large B-cell lymphoma and classical lymphoma;
• Hodgkin's B-cell with a morphology intermediate between Burkitt's lymphoma and diffuse large B-cell lymphoma.

T-cell and NK-cell lymphomas:

• T-cell precursor lymphomas;
• T-lymphoblastic lymphoma / leukemia;
• Lymphomas from mature T and NK cells;
• Osp-like lymphoma;
• Adult non-Hodgkin T cell lymphoma;
• Extranodal NK / T cell lymphoma, nasal type;
• T-cell Hodgkin's lymphoma associated with enteropathy;
• Hepatosplenic T-cell lymphoma;
• Subcutaneous panniculopathy T-cell lymphoma;
• Fungal mycosis / Sesari's syndrome;
• Primary cutaneous anaplastic large cell lymphoma;
• Primary cutaneous gamma-delta T-cell lymphoma;
• Primary cutaneous CD4 positive small and medium cell T-cell lymphoma;
• Primary cutaneous aggressive epidermotropic CD8 positive cytotoxic T-cell lymphoma;
• Peripheral T-cell lymphoma, nonspecific;
• Angioimmunoblastic T-cell lymphoma;
• Anaplastic large cell lymphoma ALK-positive;
• Anaplastic large cell lymphoma ALK-negative.

Diagnosis and treatment of the disease

It is carried out in clinics specializing in oncological diseases and blood diseases. To determine the right type of non-Hodgkin's lymphoma, you need to do many tests, including blood tests, ultrasound, x-rays, and excisional biopsies of the earliest lymph node. It is removed completely. When removed, it must not be damaged mechanically. It is not recommended to remove LNs in the groin for histological examination if there are other groups of LNs involved in the process.

Tumor tissue examination

If non-Hodgkin's lymphoma is suspected by preliminary analyzes, diagnosis and treatment in the future will depend on the results of a comprehensive additional diagnosis:

• Surgically, the affected organ tissue is taken or the LN is removed.
• When fluid accumulates in cavities, for example, in the abdominal cavity, the fluid is examined. It is taken with a puncture.
• Bone marrow puncture is performed to examine the bone marrow.

According to the results of cytological, immunological and genetic analyzes, immunophenotyping, the pathology is confirmed or not, its form is determined. Immunophenotyping is performed by flow cytometry or immunohistochemical methods.

If a comprehensive diagnosis of lymphoma confirms NHL, then experts determine its prevalence in the body to draw up a treatment regimen. For this, ultrasound and X-ray images, MRI and CT are examined. Additional information is obtained from PET - positron emission tomography. The presence of tumor cells in the central nervous system is recognized by a sample of cerebrospinal fluid (CSF) using a lumbar puncture. For the same purpose, children undergo bone marrow puncture.

Pre-treatment studies

Children and adults are tested for the work of the heart using an ECG - electrocardiogram and EchoCG - an echocardiogram. Find out if NHL affected the function of any organ, metabolism, and whether infections are present.

Initial test results are very important in the event of any changes in NHL treatment. Treatment for lymphoma is not complete without blood transfusions. Therefore, the patient's blood group is immediately established.

Drawing up treatment regimens

After confirming the diagnosis by doctors, an individual treatment regimen is drawn up for each patient, taking into account certain prognostic and risk factors that affect the prognosis of the patient's survival.

The following are considered important prognostic factors and criteria affecting the course of treatment:

• a specific form of NHL, depending on which a treatment protocol is made;
• the scale of the spread of the disease throughout the body, stage. The intensity of treatment and duration depends on this.

Surgery for non-Hodgkin's lymphoma

Surgery for NHL is not often performed, only in the case of removal of part of the tumor and with the aim of removing tissue samples to clarify the diagnosis. If there is an isolated lesion of an organ, for example, stomach or liver, then surgery is used. But more often, preference is given to radiation.

Treatment of Non-Hodgkin's Lymphomas by Risk Group

With non-Hodgkin's lymphomas, treatment is complex.

To develop the basic principles for the treatment of non-Hodgkin's lymphomas, each individual clinical situation is repeatedly assessed and accumulated experience in the treatment of indolent and aggressive NHL. This has become the foundation of approaches to therapy. Treatment of lymphoma should take into account the intoxication of the body (A or B), extranodal lesions (E) and lesions of the spleen (S), the volume of tumor foci. Differences in the prognosis of the results of aggressive chemotherapy and radiation therapy (RT) at stages III and IV are important compared with the results observed in Hodgkin's lymphoma.

To prescribe treatment, stage III tumors were divided into:

• III - 1 - taking into account the lesions on both sides of the diaphragm, limited by the involvement of the spleen, chilar, celiac and portal lymph nodes;
• III - 2 - including paraortal, iliac or mesenteric LN.

Is lymphoma treated? It is known that in patients over 60 years of age at the first stage, the proliferative disease proceeds relatively well, and at the fourth stage they have a high level of lactate dehydrogenase (LDH) in the blood and a poor prognosis of survival. To choose the principle and increase the aggressiveness of treatment, the largest volume of tumor masses was considered: peripheral, nodal lesions - 10 cm or more in diameter, and the ratio of the diameter of enlarged mediastal LN to the transverse dimensions of the chest was more than 0.33. In special cases, an unfavorable prognostic sign influencing the choice of therapy is considered for nodal lesions to be the largest tumor size - 5 cm in diameter.

The principle of choice of therapy is influenced by another 5 unfavorable risk factors, which were combined by the International Prognostic Index (IPI):

• age 60 years or more;
• an increased level of LDH in the blood (2 times more than the norm);
• general status\u003e 1 (2–4) on the ECOG scale;
• stages III and IV;
• number of extranodal lesions\u003e 1.

1. Group 1 - low level (presence of 0-1 signs);
2. Group 2 - low intermediate level (presence of 2 signs);
3. Group 3 - high intermediate level (presence of 3 signs);
4. Group 4 - high level (presence of 4-5 signs).

For patients under 60 years of age with aggressive NHL, a different MPI model is used and other 4 risk categories have been identified for 3 unfavorable factors:

• stages III and IV;
• increased serum LDH concentration;
• overall status on the ECOG scale\u003e 1 (2–4).

1. Category 1 - low risk in the absence of (0) factors;
2. Category 2 - low intermediate risk with one risk factor;
3. Category 3 - high intermediate risk with two factors;
4. Category 4 - high risk with three factors.

The survival rate for 5 years in accordance with the categories will be - 83%, 69%, 46% and 32%.

Scientists oncologists explaining what it is and how it is treated, believe that the risk indicators for MFI influence the choice of treatment not only for aggressive NHL in general, but also for any form of NHL and in any clinical situation.

The original treatment algorithm for indolent NHL was that it was for B-cell lymphomas. More often for follicular tumors of I and II degrees. But in 20-30% of cases, they are transformed into diffuse large B-cells. And this requires a different treatment, corresponding to the fundamental treatment of aggressive forms, which include grade III follicular NHL.

The main treatment for non-Hodgkin's lymphomas is with the use of combinations of cytostatic drugs. Treatment is often carried out in short courses, the intervals between them are 2-3 weeks. To determine the sensitivity of the tumor to each specific type of chemotherapy, exactly 2 treatment cycles are carried out, at least. If there is no effect, then the lymphoma is treated with another chemotherapy regimen.

Change the chemotherapy regimen if, after a significant decrease in the size of the LN, they increase in the interval between cycles. This indicates the resistance of the tumor to the combination of cytostatics used.

If the long-awaited effect from the standard chemistry regimen does not occur, a high-dose one is performed and hematopoietic stem cells are transplanted. With high-dose chemistry, high doses of cytostatics are prescribed, which kill even the most resistant and persistent lymphoma cells. Moreover, this treatment is capable of destroying hematopoiesis in the bone marrow. Therefore, stem cells are transferred into the hematopoietic system to restore the destroyed bone marrow, i.e. allogeneic stem cell transplantation is performed.

It's important to know! In allogeneic transplantation, stem cells or bone marrow are taken from another person (from a compatible donor). It is less toxic and more frequent. In autologous transplantation, stem cells are taken from the patient before high-dose chemotherapy.

Cytostatics are administered by transfusion (infusion) or intravenous injections. As a result of systemic chemotherapy, the drug is carried throughout the body through the vessels and fights lymphoma cells. If the central nervous system is suspected or the test results indicate this, then in addition to systemic chemistry, the drug is injected directly into the brain fluid, i.e. intrathecal chemistry is performed.

Cerebral fluid is found in the space around the spinal cord and brain. The blood-brain barrier, which protects the brain, does not allow cytostatics to pass through the blood vessels to the brain tissues. Therefore, intratectal chemistry is important for patients.

To increase the effectiveness of treatment, they are additionally used. NHL is a systemic disease that can affect the entire body. Therefore, it is impossible to cure with one surgical intervention. The operation is used for diagnostic purposes only. If a small tumor is found, it is removed promptly and a less intensive course of chemistry is prescribed. They completely abandon cytostatics only in the presence of tumor cells on the skin.

Biological treatment

Biological products: serums, vaccines, proteins replace natural substances produced by the body. Protein drugs that stimulate the production and growth of blood stem cells include, for example, Filgrastrim. They are used after chemotherapy to restore hematopoiesis and reduce the risk of infections.

Cytokines such as Interferon-alpha treat skin T-cell lymphomas and hairy cell leukemia. Special white cells - monoclonal antibodies bind to antigens that are located on the surface of the tumor cell. Due to this, the cell dies. Therapeutic antibodies bind to antigens dissolved in the blood and are not bound to cells.

These antigens promote tumor growth. Then used in therapy - a monoclonal antibody. Biological treatment enhances the effect of standard chemotherapy and prolongs remission. Monoclonal therapy is referred to as immune therapy. Its various types activate the immune system so much that it itself begins to destroy cancer cells.

Tumor vaccines are capable of eliciting an active immune response against proteins specific to tumor cells. The new species is being actively explored with CC T cells loaded with chimeric antigen receptors that will act against a given target.

Radioimmunotherapy acts with monoclonal therapeutic antibodies combined with a radioactive substance (radioisotope). When monoclonal antibodies bind to tumor cells, they die under the influence of a radioisotope.

Informative video

Nutrition for Non-Hodgkin Lymphomas

Nutrition for non-Hodgkin's lymphoma should be as follows:

• adequate in terms of energy consumption to avoid weight gain;
• as diverse as possible: with vegetables and fruits, meat of animals, birds, fish and products derived from it, with seafood and herbs.
• with a minimum consumption of pickles and sauerkraut products, table (sea or table) salt, smoked meats.

Food should be tasty, frequent and small doses. Each patient should be approached individually so as not to exclude hypernatremia (excess sodium salts). This traps fluid in the body and forms edema. At the same time, salt and smoked meats should be excluded so as not to increase the salt K in the blood. If the patient cannot eat fresh food, his appetite spoils, then a minimum amount of caviar, olives and other pickles can be added to the menu, but in combination with drugs that remove sodium. It should be borne in mind that after chemistry with diarrhea and vomiting, sodium salts, on the contrary, are very necessary for the body.

Alternative treatment

Includes: tinctures, infusions and decoctions of mushrooms and herbs. Effective infusions of wormwood, cocklebur, hemlock, Dzhungarian aconite, black henbane.

The following mushrooms have medicinal anti-cancer properties: birch chaga, reishi, cordyceps, meitake and shiitake, Brazilian agaric. They prevent metastases, normalize hormones, and reduce the side effects of chemotherapy: hair loss, pain and nausea.

To remove tumor toxins, crushed chaga (birch mushroom) is mixed with the chopped root of the mountaineer snake (3 tbsp each) and poured with vodka (strong moonshine) - 0.5 l. Let it brew for 3 weeks in the dark and take 30-40 drops 3-6 times a day.

The active substance Leutinan, amino acids and polysaccharides of the Reishi mushroom in combination with the substances of the Shiitake mushroom activate specific immunity and restore the blood formula.

Birch tar (100 g) should be washed 9 times in water, then grind with ammonia powder (10 g) and flour calcined in a pan. Form the dough into balls 0.5 cm in diameter. You can store them in a cardboard box, after sprinkling them with flour. The first three days, take 1 ball 4 times 60 minutes before meals. Drink with herbal decoction - 100 ml.

Broth: mix the crushed herb of the pharmacy agrimony with plantain (leaves), calendula (flowers) - all 50 grams each. Cook (10 minutes) in 600 ml of water 3 tbsp. l. collection. Let it cool a little, then drink with lemon and honey.

Survival prognosis for non-Hodgkin lymphoma

Many patients and their relatives are interested in the question of how long do patients live with this or that type of non-Hodgkin's lymphoma? The prognosis depends on the subspecies of the disease, the stage and degree of its spread throughout the body. The classification of this disease has 50 types of lymphomas.

According to research, the table shows life expectancy for non-Hodgkin's lymphomas after 5 years of treatment.

5 - YEARS SURVIVAL IN DIFFERENT TYPES OF NON-HODGKIN'S LYMPHOMA (REAL) DEPENDING ON ADVERSE FACTORS
OPTION NHL	% Of TOTAL PATIENTS	5 - YEARS SURVIVAL (% of patients)
		0-1 FACTORS	(SIMULTANEOUSLY) 4 FACTORS
Follicular	75	83	12
Marginal zone	70	90	52
Mantle zone	29	58	12
Diffuse large B-cell	45	72	22
Peripheral T-cell	26	64	15
Anaplastic large cell	77	80	77

Malignant pathology of the lymphatic system is initially divided into two groups: Hodgkin's lymphoma (lymphogranulomatosis) and non-Hodgkin's lymphoma. Approximately 80% of lymphomas are in the first group. Non-Hodgkins only account for 20%.

Non-Hodgkin's lymphoma has symptoms

In addition to classifying lymphomas by stage, doctors use an additional classification:
... A - the patient has no symptoms of the disease.
... B - patients have these symptoms.
This helps the specialist who sees the patient for the first time to quickly draw conclusions about the severity of his illness.
Symptoms for the diagnosis:
... rapid weight loss for no apparent reason;
... an increase in body temperature to subfebrile numbers (it does not go away over time and can be elevated for several weeks and months);
... increased sweating at night.
If the disease affects any internal organ, then other manifestations specific to different organs may be added. Therefore, it can disguise itself as a different pathology and lead the doctor off the right path in the diagnostic search.
If the patient sees an additional letter "E" in the indication of the diagnosis, this indicates that the lymphoma in this patient initially arose not in the lymph node, but in another organ. These forms of lymphomas are called extranodular.
If the diagnostic process is completed, and doctors were able to establish the type of lymphoma, the stage of cancer in which it is located, the degree of its malignancy, then the doctors draw up a treatment plan and proceed to the next stage.

Diagnostics

What is the difference between Hodgkin's and non-Hodgkin's lymphoma? There is only one way to distinguish these lymphomas from each other. First, a certain amount of tumor tissue is taken from the suspicious area. The cells are stained using special technologies and examined under a microscope. They can also be affected by special proteins. The technique is called immunohistochemistry.
Reed-Sternberg cells (specific to this type of tumor) are often found in material obtained from patients with Hodgkin's disease. Non-Hodgkin's lymphoma does not have these cells. It may seem that there are practically no differences between diseases, but this is not at all the case. The treatment process for patients with different types of lymphomas is very different. Non-Hodgkin's lymphomas combine more than 20 diseases, and each of them has its own characteristics and specific symptoms.
Also, non-Hodgkin's lymphomas differ from each other in specific cellular elements. Different diseases are characterized by the presence of different proteins. In different lymphomas, not only the clinical picture can be very different, but also the principles of their treatment.

Grades of malignancy of non-Hodgkin's lymphoma

It is very important in the process of diagnostics to correctly establish the stage of development of the disease and its exact type. This allows doctors to predict the course of the disease and take adequate measures.
Doctors need to know the degree of malignancy in order to understand how aggressively the disease will continue and at what speed it will develop. All non-Hodgkin's lymphomas fall into two categories according to this criterion:
... with a high degree of aggressiveness;
... with a low degree of aggressiveness.
With a low degree of aggressiveness calls it sluggish. It progresses very slowly and does not require radical treatment. An oncologist can observe a patient with such a disease for more than one year and not see a reason for prescribing treatment. If therapy is started, then the tumor quickly decreases in size or even completely disappears. Some lymphomas in this group are permanently cured, and some may recur and bother the patient again.
Sluggish lymphomas include:
... follicular lymphoma;
... lymphoma from cells of the mantle zone;
... lymphoplasmacytic lymphoma;
... lymphoma of the marginal zone.
progress rapidly and cause more pronounced clinical symptoms. Once they are found in a patient, the treatment process begins. Otherwise valuable time may be wasted and further effects will not be as good. Up to death.
Aggressive lymphomas are:
... diffuse large B-cell lymphoma;
... Burkit's lymphoma;
... large cell anaplastic lymphoma.
Unfortunately, low-grade non-Hodgkin's lymphoma can unexpectedly change its course for the patient and begin to progress extremely rapidly. According to statistics, this phenomenon is observed in about a third of patients with sluggish forms of the disease. Of course, certain of the sluggish non-Hodgkin's lymphomas have a tendency to accelerate progression, which doctors have already noticed. Therefore, they try to treat patients with such diseases as quickly as possible, without waiting for the situation to change.
The transition to another form can take up to several years. These non-Hodgkin's lymphomas are treated according to the same principles as initially aggressive. In some cases, doctors find in one patient and sluggish and aggressive forms of the disease. In this case, doctors act on the same principles as when treating initially aggressive lymphoma.

Disease stages

The stages of the disease are exhibited depending on how widespread the malignant process is. To establish the stage, doctors also need information about where the focus is located and how many lymph nodes are affected by metastases. It also takes into account whether the lymphoma has spread to internal organs and nodes in other anatomical areas.
The most popular and simplest is the following classification:
... Stage 1 - enlarged regional lymph nodes belonging to the same group.
... Stage 2 - two groups of nodes have already been changed, but the pathological process does not extend to the other side of the diaphragm (all nodes are either below or above). The diaphragm is a broad muscle that separates the abdominal cavity from the chest and takes part in the act of breathing. Everything above it is considered to be the upper half of the body, and everything below it is the lower half.
... Stage 3 cancer - the lymph nodes are enlarged on either side of the diaphragm.
... Stage 4 cancer - spread beyond the nodes and damage to internal organs: liver, lungs, spleen, etc.

New treatment regimens

Since pathology is very relevant to this day, a lot of research is being carried out around the world to find new methods of treatment. This led to the discovery of new drugs and the introduction of new treatment regimens. As a result, lymphoma has been treated more effectively in recent years. Nowadays, doctors can achieve a good result even when the disease has left the lymph nodes and affected other organs. Now many more patients are recovering after the course of treatment, and remission lasts for many years.
In the case of a disease such as lymphoma, doctors refer to recovery as remission. Remission - this is the absence of manifestations of the disease, both morphological and clinical. In fact, this is the state of a healthy person. If we talk about partial remission, then they mean a decrease in tumor size and an improvement in the patient's well-being. Such people do not suffer from the manifestations of the disease and do not need treatment at a certain stage.

Immunotherapy for non-Hodgkin's lymphoma

Immunotherapy drugs are used to treat different subtypes of lymphomas. This allows you to achieve the best result and not burden the body with less effective means.

• Substances that act on the DNA of cancer cells. As a result of their damage, tumor growth stops and regression occurs.
• Antibiotics with antitumor activity.
• Drugs that block the ability to build nucleic acids - antimetabolites.
• Proteasome inhibitors - lead to a decrease in the ability of the cell to withstand adverse factors.
• Inhibitors of enzymes and proteins responsible for DNA repair. As a result, the genetic material of the cell remains defenseless and it loses its ability to reproduce and dies.
• Inhibitors of mitosis - the process of cell division. It is thanks to these drugs that the cells multiply and the tumor grows.
• Cortisol-based hormones - in large quantities, they can effectively destroy lymphocytes.
• Special monoclonal antibodies - destroy cancer cells and have an order of magnitude fewer side effects than traditional chemotherapy drugs.

Non-Hodgkin's lymphoma with a low degree of aggressiveness
Treatment of these forms can be postponed indefinitely and the patient can be observed. This tactic is called watchful waiting or active observation.
If we talk about a sluggish form, then such therapy is adequate for it - a combination of monoclonal antibodies with chemotherapy drugs. When a patient is found to have lymphoma that affects only one group of nodes in one anatomical region, doctors most often prefer to carry out local radiation therapy. This allows you to influence the tumor and not expose the entire body to the effects of chemotherapy drugs injected into the systemic circulation.
In most cases, after such treatment, the patient is in remission. When the disease returns, a course of treatment with monoclonal antibodies is carried out. This allows you to keep the disease under control for a long time.
With a high degree of aggressiveness
These forms are treated with higher doses of drugs. Drugs are injected into the bloodstream and antibodies are additionally used. Such patients can be treated at a day hospital. If necessary, doctors will recommend hospitalization for a while. If, as a result of the progression of the disease, the central nervous system is affected, then drugs can be injected directly into the spinal canal, using a puncture. Sometimes aggressive lymphoma is more sensitive to treatment than indolent lymphoma.
If doctors believe that the risk of recurrence remains at a high level, then the patient is given additional measures (therapy with high doses of the drug, radiotherapy).

Radiotherapy

For lymphomas, doctors use local radiotherapy. As a rule, a group of lymph nodes affected by the disease is irradiated. It is advisable to carry out such treatment if no more than 2 groups of nodes are affected and they are located on one side of the diaphragm. Sometimes radiotherapy is combined with other treatments.
The entire course is a series of short sessions conducted daily in a dedicated unit. The amount of exposure is determined by the doctor.

Chemotherapy

If the disease is sluggish and relatively easy, then the patient can be treated in the form of tablets. As a result, the medical professional does not need to inject the drug on his own, the patient takes the pills at home, which eliminates the need to stay in the clinic.
Sometimes the drug is given intravenously. Then the patient must visit a healthcare facility to receive treatment. Because Since drugs have a number of side effects, some patients need a day hospital. This gives doctors the opportunity to monitor the patient around the clock.
Chlorambucil is a drug often prescribed to patients in tablets. Fludarabine is often used (it can be in a tablet or as a solution). CVP is a combination of drugs. This includes cyclophosphamide, vincristine, and prednisolone.
With an aggressive disease
In order to effectively treat such forms of the disease, doctors resort to intravenous administration of the drug. The patient receives treatment with chemotherapy for several days, after which a break is made, lasting several weeks. During this time, the substances exert their effect, and healthy tissues recover from the impact that was exerted on them. Unfortunately, the high efficiency of the drug often comes at the cost of many side effects. The entire course of treatment takes several months. Throughout this time, the patient undergoes tests, the purpose of which is to control the effectiveness of treatment.
There are chemotherapy regimens that provide for the administration of the drug once a week for several months without interruption, since the body tolerates such a rare exposure well.
Aggressive lymphomas are treated with a combination of drugs. Nowadays, CHOR is generally accepted - a combination of four chemotherapy drugs. In addition to it, monoclonal antibodies can be prescribed if there is a reason.

Injection of chemotherapy drugs into the spinal canal

If damage to the structures of the central nervous system occurs, then the treatment is somewhat different from the standard one. For this, a lumbar puncture is performed and the cerebrospinal fluid is taken for analysis. If abnormal cells are found there, then doctors prescribe an intrathecal injection of a chemotherapy drug. This allows the drug to be delivered directly to its destination, bypassing the blood-brain barrier. Such treatment can be performed on an outpatient basis, but it is better to hospitalize the patient for a short time. The fact is that the complications of such treatment can be very serious.
So drugs can be administered not only if there are abnormal cells in the cerebrospinal fluid. If the cells are not detected, but there are all symptoms indicating damage to the structures of the central nervous system, then intrathecal administration is possible.

Non-Hodgkin's lymphoma is one of the most common types of cancer, affecting hundreds of people around the world. To understand how to recognize a disease and treat it, you must first understand what it is.

Non-Hodgkin's lymphoma is a collective concept, it denotes a whole group of oncological diseases in which malignant cells affect lymphoid tissues. In other words, this category includes all types of existing lymphomas with the exception of Hodgkin's lymphoma. A distinctive characteristic of the latter is the presence of altered and multinucleated cells in the affected tissues.

Features of the disease

About 80 different diseases belong to non-Hodgkonian lymphomas, which differ in their aggressiveness and localization.

There are approximately the same number of men and women among patients, although in some types of the disease there is still a dependence on gender. As for the age categories, older people have a slightly higher risk of developing cancer. Meanwhile, the disease is often diagnosed in children.

Since non-Hodgkin's lymphomas are not one but many diseases united by one characteristic, several forms and varieties should be considered at once. The characteristics of the disease will directly depend on such features as the duration and intensity of the course of therapy, the prognosis of treatment and possible

B-cell form

The most common type of classification can be considered the one adopted by the World Health Organization. It is based precisely on the cellular composition of oncology. There are 2 broad categories here: B-cell and T-cell lymphomas. Each of them should be mentioned in more detail.

What is B-cell non-Hodgkin's lymphoma? This is a malignant disease of lymphoid tissue in which B-lymphocytes are affected. Their main task is to produce antibodies, therefore, they are involved in the immune humoral response. Several types of lymphomas can be distinguished here:

1. Nodal and splenic. These species are slow growing.
2. Burkitt's lymphoma. According to medical statistics, it is men who are about 30 years old who most often suffer from this form of the disease. Doctors are in no hurry to give favorable predictions: with Burkitt's non-Hodgkin lymphoma, the survival rate of patients within 5 years is only 50%.
3. Follicular. In most cases, this cancer develops rather slowly, but it can turn into a diffuse form, which is characterized by rapid development.
4. Lymphoma MALT of the marginal zone. This form spreads to the stomach and increases at a slow rate. With all this, it is extremely difficult to treat it.
5. Primary mediastinal (or mediastinal). This disease most often affects women, 5-year survival rate after treatment is 50%.
6. Small cell lymphocentric. Development is slow, but the cure rate is quite low.
7. Primary CNS lymphoma.
8. Diffuse non-Hodgkin's lymphoma is large cell. This type refers to rapidly progressing oncological diseases.

Varieties of non-Hodgkin T-cell lymphoma

T-cell lymphoma is understood as a malignant disease during which an uncontrolled growth of T-lymphocytes occurs. Their production takes place in the thymus and they support the cellular (or barrier) immunity of the skin and mucous membranes.

• Lymphoblastic form. Most of the patients with this diagnosis are young men under 40. A favorable outcome of treatment is predicted only if the bone marrow is not involved in the process.
• Large cell non-Hodgkin's lymphoma is anaplastic. Most often, this disease occurs in young people, but with timely diagnosis, it responds well to treatment.
• Extranodal NHL. This form of the disease affects killer T cells, and its aggressiveness can vary.
• Cesari syndrome (or cutaneous). This form is often called fungal mycosis and is formed mainly in older people (50-60 years old).
• Lymphoma with enteropathy. It has been noticed that this type of cancer is typical for people with gluten intolerance. It is characterized as extremely aggressive and difficult to treat.
• Angioimmunoblastic. This type is difficult to treat, and therefore doctors do not make favorable predictions for life.
• Non-Hodgkin's lymphoma is panniculitis-like. Such oncology develops in the subcutaneous fat. A characteristic feature of this form is considered to be low sensitivity to chemotherapy, which makes the treatment ineffective.

Types of aggressiveness

Another option for the classification of neodzhkin lymphomas is the division according to the aggressiveness of the process. This is very convenient for doctors, as it allows you to optimally select a course of treatment and observation tactics.

• Aggressive NHL. This type includes oncological diseases with rapid development, active spread and, in some cases, with resistance to chemotherapy. The prognosis of treatment here can be made based mainly on the stage of oncology at which non-Hodgkin's lymphoma was detected. Relapses of these forms of the disease occur quite often.
• Indolent. Unlike the previous form, indolent lymphoma grows slowly and metastasizes. Sometimes cancers of this form may not manifest themselves for years (that is, they do not cause painful sensations and other symptoms of pathology in a person). In general, with timely treatment of non-Hodgkin's lymphoma, the prognosis here is quite good.
• Intermediate. These types of diseases begin to develop slowly, but over time they increase the pace, tending more to aggressive forms.

Development reasons

Until now, doctors have not been able to accurately identify the factors provoking the development of non-Hodgkin's lymphoma of any type. However, the following point should be considered here. According to its origin, the disease is divided into:

• primary - oncology primarily affects lymphoid tissues (an independent focus), and then gives metastases to other organs;
• secondary - in this case, the disease appears in the form of metastases, therefore, the reason can be called the presence of malignant cells in the body.

If we talk about the causes of primary lymphoma, then in medicine there are several factors:

• Infections in the body. The hepatitis C virus, HIV infection or human herpes virus (type 8) can provoke the appearance of abnormal cells. The Epstein-Barr virus often causes Burkitt's lymphoma, or the follicular form of the disease. People exposed to the bacteria Helicobacter pylori (which causes stomach ulcers) have a markedly increased risk of developing MALT lymphoma.
• Certain genetic diseases. Among them are: ataxia-telangiectasia syndrome, Chédiak-Higashi, and Klinefelter's syndrome.
• Ionized radiation at any dose.
• The effect of benzenes, insecticides, herbicides and many other mutagens or chemical carcinogens.
• Diseases of an autoimmune nature. A typical example would be rheumatoid arthritis or systemic lupus erythematosus.
• Long-term use of various immunosuppressants.
• Age-related changes in body tissues. The risk of developing non-Hodgkin's lymphoma increases markedly with age. A doctor's recommendation to reduce this risk is to get regular check-ups. This will make it possible to identify the disease at an early stage and start treatment in a timely manner.
• Overweight.

It should be noted that the presence of one or several factors from the above list does not mean the inevitable development of oncological diseases. They only increase the risk of its occurrence.

Lymphoma stages

The entire period of the course of oncological disease is usually divided into 4 stages (stages), and lymphoma in this case is no exception.

Stage 1. Non-Hodgkin's lymphoma at this stage is represented by the defeat of one lymph node or the appearance of one independent focus. Local manifestations have not yet been observed.

Stage 2. This stage includes a malignant neoplasm that has spread to two or more lymph nodes and has also gone beyond the lymph nodes, but is localized only on one side of the diaphragm. So, the tumor can spread either only in the abdominal cavity or only in the chest.

Stage 3. The next stage of development is the presence of foci on both sides of the diaphragm.

Stage 4. This stage of development of lymphoma is considered the last one. At this time, the lesion spreads to the bone marrow, skeleton and central nervous system. This stage is not in vain considered the last and most difficult for the patient. One of the manifestations is constant severe pain, which can no longer be stopped with the help of conventional analgesics.

Clinical picture

The symptoms of non-Hodgkin's lymphoma are very diverse and depend on the form of the disease and the location. A common symptom of malignant lymphoid tissue is enlargement of the lymph nodes (widespread or local) and pain in this area. This condition is accompanied by symptoms of damage to a specific organ or signs of general intoxication of the body.

T-cell forms often manifest themselves as follows:

• increase;
• there is an increase in the spleen and a violation of its work;
• lungs and skin are damaged.

There are several symptoms that are common in non-Hodgkin's lymphomas but are absent in Hodgkin's lymphoma. Among them:

• damage to the lymph nodes of the mediastinum (the space of the chest cavity), there is swelling of the face and hyperemia (excessive blood flow to a certain part of the body);
• if malignant cells develop in the thymus, there is frequent shortness of breath and cough;
• enlargement of the pelvic or retroperitoneal lymph nodes provokes renal failure or hydronephrosis (gradual atrophy of the kidneys).

At the same time, one cannot fail to note the symptoms that accompany any oncological disease. With non-Hodgkin lymphoma, they begin to appear at stage 2 of the disease and gradually become brighter:

• a sharp decrease in working capacity, the appearance of weakness and rapid fatigue;
• lack of appetite;
• weight loss;
• the appearance of irritability, apathy;
• persistent heavy sweating, mainly at night;
• signs of anemia.

Diagnosing lymphomas

An increase in lymph nodes indicates not only an oncological disease, but also the presence of an infection in the human body. If an infectious component is suspected, the patient is prescribed a drug designed to eliminate the focus. After a while, the inspection is repeated. If no improvement is observed, a number of laboratory tests and instrumental diagnostic procedures are prescribed. The doctor will choose the principles and methods of treatment for non-Hodgkin's lymphoma based on the examination data.

• Blood tests to determine the state of the body and search for pathology.
• Chest X-ray. According to the results of this procedure, the condition of the lymph nodes of the chest is revealed.
• CT - computed tomography provides information about the state of all lymph nodes and the possible presence of metastases in other organs.
• MRI. With the help of magnetic resonance imaging, doctors determine the current state of the spinal cord and brain and the possible presence of malignant cells in them.
• PAT. This term hides the diagnostic procedure positron emission tomography. During it, a special substance is injected into the patient's vein to help identify all cancerous foci in soft tissues.
• Gallium scan. This method effectively complements PET, as it detects malignant cells in the bone tissue.
• Ultrasound gives information about the state of internal organs.
• Biopsy. This diagnosis is the extraction of tumor cells and their further examination in the laboratory. Biopsy can be performed in different ways, therefore, incisional, excisional, puncture, spinal puncture and bone marrow aspiration are distinguished.

Treatment

In each case, the course of treatment is prescribed taking into account the results of the diagnosis. Some forms of lymphoma do not need treatment at first (this includes types of tumors with slow development and no pronounced symptoms).

Chemotherapy. For non-Hodgkin's lymphoma, multiple courses of chemotherapy are given. The therapeutic effect is achieved with the use of strong anticancer drugs, which are designed to block the growth and reproduction of pathological cells. The interval between courses is about 2 or 4 weeks. Dosage form: intravenous solutions or tablets.

Radiation therapy. The essence of the treatment comes down to the effect on the human body of ionized rays, which are destructive for a cancer. Such treatment for non-Hodgkin's lymphoma is in some cases the main one, but most often it is combined with chemotherapy.

Surgery. In the case of lymphomas, surgery is rarely used due to its low efficiency. Its purpose makes sense only in the case of a limited spread of the tumor.

Immunotherapy. Treatment of non-Hodgkin's lymphoma is often carried out with drugs that contain interferon, monoclonal antibodies, and chemotherapy drugs. The essence of such an effect is to supply the body with those substances that the human body produces independently under normal conditions. Such medicines significantly reduce the size of the tumor, slow down its growth and dramatically increase the human immunity to fight the disease.

Bone marrow transplant. This therapy is used when other treatments fail. Before the transplant, the patient undergoes high-dose radiation or chemotherapy. Subsequent transplantation is required because high doses of radiation or drugs kill not only cancer cells, but also healthy tissue. It is to restore the bone marrow that transplantation is prescribed.

Important! Self-medication with such a diagnosis is strictly prohibited! Lymphomas of any type and nature are not treated with folk remedies; this requires a professional approach and a set of measures to eliminate the tumor.

Forecast

As medical statistics and medical reviews show, non-Hodgkin's lymphoma is effectively treated at stages 1 and 2 of development. In this case, the survival rate of patients over the next 5 years is about 80%. This is a fairly high figure given the severity of the disease. In the case of patients with stage 3 oncology, the survival rate is lower, since the tumor has time to spread far beyond the focus, and it is much more difficult to cope with it. At stage 4, the survival rate is low - only 20%.

Doctors emphasize: even constant development and research in this area does not allow treating oncological diseases with 100% efficiency. That is why a lot depends on the patient himself. Early detection of the symptoms of the disease and going to the clinic significantly increase the chance of a full recovery.

Non-Hodgkin's lymphomas are a heterogeneous group of diseases characterized by the monoclonal proliferation of malignant lymphoid cells in the lymphoreticular regions, including lymph nodes, bone marrow, spleen, liver, and gastrointestinal tract.

The disease usually presents with peripheral lymphadenopathy. However, in some forms, there is no enlargement of the lymph nodes, but there are abnormal lymphocytes in the circulating blood. Unlike Hodgkin's lymphoma, the disease is characterized by dissemination of the process at the time of diagnosis. The diagnosis is based on a lymph node or bone marrow biopsy. Treatment includes radiation and / or chemotherapy, and stem cell transplantation is usually performed as salvage therapy for incomplete remission or relapse of the disease.

Non-Hodgkin's lymphoma is more common than Hodgkin's lymphoma. It is the 6th most common cancer in the United States, and about 56,000 new cases of non-Hodgkin's lymphomas are reported annually across all age groups. However, non-Hodgkin's lymphoma is not a single disease, but an entire category of lymphoproliferative malignant diseases. The incidence increases with age (median age is 50 years).

ICD-10 code

C82 Follicular [nodular] non-Hodgkin's lymphoma

C83 Diffuse non-Hodgkin's lymphoma

Causes of non-Hodgkin lymphomas

The majority of non-Hodgkin's lymphomas (80 to 85%) originate from B cells, in the rest of the cases, the source of the tumor is T cells or natural killer cells. In all cases, the source is early or mature progenitor cells.

The cause of non-Hodgkin's lymphomas is unknown, although, as with leukemias, there are strong indications of a viral nature of the disease (eg, human T-cell leukemia / lymphoma virus, Epstein-Barr virus, HIV). Risk factors for the development of non-Hodgkin's lymphomas are immunodeficiency (secondary post-transplant immunosuppression, AIDS, primary immune diseases, dry eye syndrome, RA), infection Helicobacter pylori,exposure to certain chemicals, previous treatments for Hodgkin's lymphoma. Non-Hodgkin's lymphomas are the second most common cancer in HIV-infected patients, and AIDS is defined in many primary patients with lymphoma. Rearrangement S-tuscharacteristic of some AIDS-associated lymphomas.

Leukemias and non-Hodgkin's lymphomas have many common features, since in both pathologies, lymphocytes or their precursors proliferate. In some types of non-Hodgkin's lymphomas, a clinical picture similar to leukemia with peripheral lymphocytosis and bone marrow involvement is present in 50% of children and 20% of adults. Differential diagnosis can be difficult, but usually in patients with many lymph nodes (especially mediastinum), a small number of circulating abnormal cells and blast forms in the bone marrow (

Hypogammaglobulinemia, caused by a progressive decrease in immunoglobulin production, occurs in 15% of patients and can predispose to the development of severe bacterial infections.

Symptoms of non-Hodgkin lymphomas

In many patients, the disease manifests itself as asymptomatic peripheral lymphadenopathy. The enlarged lymph nodes are elastic and mobile, later they merge into conglomerates. In some patients, the disease is localized, but the majority have multiple lesions. Mediastinal and retroperitoneal lymphadenopathy can cause compression symptoms in various organs. Extranodal lesions may dominate the clinical picture (eg, gastric involvement may mimic cancer; bowel lymphoma may cause malabsorption syndrome; CNS is often affected in HIV patients).

Skin and bones are initially affected in 15% of patients with aggressive lymphomas and in 7% of patients with indolent lymphomas. Sometimes in patients with a pronounced process in the abdominal or chest cavity, chyle ascites or pleural effusion caused by obstruction of the lymphatic ducts develops. Weight loss, fever, night sweats, and asthenia indicate disseminated disease. Patients may also have splenomegaly and hepatomegaly.

Two signs are typical in NHL and are rare in Hodgkin's lymphoma: hyperemia and edema of the face and neck may occur due to compression of the superior vena cava (superior vena cava syndrome or superior mediastinal syndrome), compression of the ureter by the retroperitoneal and / or pelvic lymph nodes disrupts urine flow through the ureter and can lead to secondary renal failure.

Anemia initially occurs in 33% of patients and gradually develops in most patients. Anemia can be due to the following reasons: bleeding with gastrointestinal lymphoma with or without thrombocytopenia; hypersplenism or Coombs-positive hemolytic anemia; infiltration of bone marrow with lymphoma cells; myelosuppression caused by chemotherapy or radiation therapy.

T-cell lymphoma / leukemia (associated with HTLV-1) has an acute onset, rapid clinical course with skin infiltration, lymphadenopathy, hepatosplenomegaly, and leukemia. Leukemia cells are malignant T cells with altered nuclei. Hypercalcemia often develops, associated more with humoral factors than with bone damage.

Patients with anaplastic large cell lymphoma have rapidly progressive skin lesions, adenopathy, and damage to the visceral organs. This disease can be mistaken for Hodgkin's lymphoma or metastases of undifferentiated cancer.

Staging of non-Hodgkin lymphomas

Although localized non-Hodgkin's lymphomas are sometimes found, the disease is usually disseminated at the time of diagnosis. Tests for staging are CT scans of the chest, abdomen and pelvis, PET, and bone marrow biopsy. The definitive staging of non-Hodgkin's lymphomas, as in Hodgkin's lymphoma, is based on clinical and histological findings.

Classification of non-Hodgkin lymphomas

The classification of non-Hodgkin's lymphomas continues to evolve, reflecting new knowledge of the cellular nature and biological basis of these heterogeneous diseases. The most common is the WHO classification, reflecting the immunophenotype, genotype and cytogenetics of cells; there are other classification of lymphomas (for example, the Lyon classification). The most important new types of lymphomas included in the WHO classification are lymphoid tumors associated with mucous membranes; lymphoma from cells of the mantle zone (formerly diffuse from small split cells lymphoma) and anaplastic large cell lymphoma, a heterogeneous disease, in 75% of cases originating from T cells, 15% from B cells, in 10% of cases - unclassified. However, despite the variety of types of lymphomas, their treatment is often the same, except for certain types of T-cell lymphomas.

Lymphomas are usually classified as indolent and aggressive. Indolent lymphomas progress slowly and respond to therapy, but are incurable. Aggressive lymphomas progress rapidly but respond to therapy and are often curable.

In children, non-Hodgkin's lymphomas are almost always aggressive. Follicular and other indolent lymphomas are very rare. The treatment of aggressive lymphomas (Burkitt, diffuse large B-cell and lymphoblastic lymphomas) requires special approaches due to the involvement of such areas as the gastrointestinal tract (especially in the terminal ileum); the meninges and other organs (such as the brain, testes). It is also necessary to take into account the possible development of side effects of therapy, such as secondary malignant tumors, cardiorespiratory complications, as well as the need to maintain fertility. Currently, research work is aimed at solving these issues, as well as studying the development of the tumor process at the molecular level, prognostic factors for lymphoma in children.

Subtypes of non-Hodgkin's lymphoma (WHO classification)

B cell tumors

T- and NK-cell tumors

From precursors of B cells B-lymphoblastic leukemia / B-cell precursor lymphoma From mature B cells B-cell chronic lymphocytic leukemia / small cell lymphocytic lymphoma. B-cell prolymphocytic leukemia. Lymphoplasmacytic lymphoma. B-cell lymphoma from cells of the marginal zone of the spleen. Hairy cell leukemia. Plasma cell myeloma / plasmacytoma. Extranodal B-cell lymphoma of the marginal zone of lymphoid tissue (MALT lymphoma). Nodal B-cell lymphoma from cells of the marginal zone. Follicular lymphoma. Lymphoma from cells of the mantle zone. Diffuse large B-cell lymphomas. (including mediastinal large B-cell lymphoma, primary exudative lymphoma). Burkitt's lymphoma

From precursors of T cells T-lymphoblastic leukemia / lymphoma from precursor T cells. From mature T cells T-cell prolymphocytic leukemia. T-cell leukemia from large granular leukocytes. Aggressive NK cell leukemia. Adult T cell leukemia / lymphoma (HTLV1 positive). Extranodal 1MCD-cell lymphoma, nasal type. Hepatosplenic T-cell lymphoma. Subcutaneous panniculitis-like T-cell lymphoma. Fungal mycosis / Sesari's syndrome. Anaplastic large cell T / NK cell lymphoma, primary cutaneous type. Peripheral T-cell lymphoma, nonspecific. Angioimmunoblastic T-cell lymphoma

MALT is lymphoid tissue associated with mucous membranes.

NK are natural killers.

HTLV 1 (human T-cell leukemia virus 1) - human T-cell leukemia virus 1.

Aggressive.

Indolent.

Indolent, but rapidly progressing.

Diagnosis of non-Hodgkin lymphomas

Non-Hodgkin's lymphoma is suspected in patients with painless lymphadenopathy or when mediastinal adenopathy is found on routine chest x-ray. Painless lymphadenopathy can result from infectious mononucleosis, toxoplasmosis, cytomegalovirus infection, or leukemia.

Radiographic findings may be similar to lung cancer, sarcoidosis, or tuberculosis. Less commonly, the disease is detected in connection with lymphocytosis in the peripheral blood and the presence of nonspecific symptoms. In such cases, the differential diagnosis is made with leukemia, Epstein-Barr virus infection and Duncan syndrome.

A chest x-ray is performed if it has not been previously performed, as well as a lymph node biopsy if lymphadenopathy is confirmed on a CG or PET scan. In the presence of enlarged mediastinal lymph nodes, the patient needs to perform a biopsy of the lymph node under the control of CG or mediastinoscopy. The following examinations are performed as standard: complete blood count, alkaline phosphatase, renal and hepatic function tests, LDH, uric acid. Other tests are done based on preliminary findings (eg, MRI for symptoms of spinal cord compression or CNS abnormalities).

Histological criteria for biopsy are a violation of the normal structure of the lymph node and invasion of the capsule, as well as the detection of characteristic tumor cells in the adjacent adipose tissue. Immunophenotyping determines the nature of cells, identifies specific subtypes and helps to determine the prognosis and management of the patient; these studies should also be performed on peripheral blood cells. The presence of the panleukocyte antigen CD45 helps to exclude metastatic cancer, which is often found in the differential diagnosis of undifferentiated cancers. Determination of total leukocyte antigen and gene rearrangement (documenting B- or T-cell clonality) is necessarily performed on fixed tissues. Cytogenetic studies and flow cytometry require fresh biopsies.

Treatment for non-Hodgkin lymphomas

Treatment for non-Hodgkin's lymphoma varies greatly depending on the cell type of lymphoma, and there are many treatment programs that do not allow us to dwell on them in detail. Fundamentally different approaches to the treatment of localized and disseminated stages of lymphoma, as well as aggressive and indolent lymphomas.

Localized non-Hodgkin's lymphoma (stages I and II)

Indolent lymphoma is rarely diagnosed at the stage of localized lesion, but in the presence of such a lesion, regional radiation therapy can lead to long-term remission. However, more than 10 years after radiation therapy, the disease may recur.

About half of patients with aggressive lymphomas are diagnosed in the stage of localized lesions, in which polychemotherapy in combination with or without regional radiation therapy is usually effective. Patients with lymphoblastic lymphomas or Burkitt's lymphoma, even with localized lesions, should be treated with intensive chemotherapy regimens with prevention of CNS damage. Supportive therapy (for lymphoblastic lymphoma) may be required, but complete recovery is possible.

Common form of non-Hodgkin's lymphoma (stage III and IV)

There are various approaches to the treatment of indolent lymphomas. A watch-and-wait approach, therapy with one alkylating drug or a combination of 2 or 3 chemotherapy drugs, can be used. The choice of treatment strategy is based on a number of criteria, including age, general status, prevalence of the disease, tumor size, histological variation, and expected treatment efficacy. Rituximab (anti-CD20 antibodies to B cells) and other biologics that are used in combination with chemotherapy or as monotherapy are effective. Recent reports of the use of antibodies conjugated to radioisotopes are promising. Although the survival rate of patients can be calculated in years, the long-term prognosis is poor due to the occurrence of late relapses.

For patients with aggressive B-cell lymphomas (eg, diffuse large B-cell lymphoma), the standard combination is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone). Complete regression of the disease occurs in more than 70% of patients and depends on the risk category (determined by the MFI). More than 70% of patients with a complete response to treatment recover, relapses 2 years after completion of treatment are rare.

The effectiveness of the use of autologous transplantation in the first line of therapy is being studied. In accordance with the MPI, patients at high risk can be selected for therapy with dose intensification regimens. It is currently being studied whether this treatment strategy increases the chances of a cure. Individual patients with mantle cell lymphoma may also be candidates for this type of therapy.

Recurrent aggressive lymphoma

The first relapse after the first line of therapy is almost always treated with autologous hematopoietic stem cell transplantation. Patients must be younger than 70 years of age with a satisfactory general status, respond to standard chemotherapy, and have the required number of collected CD34 + stem cells (collected from peripheral blood or from bone marrow). Consolidation myeloablative therapy includes chemotherapy with or without radiation therapy. The feasibility of using immunotherapy (eg, rituximab, vaccination, IL-2) after the completion of chemotherapy is being investigated.

In allogeneic transplantation, stem cells are harvested from a compatible donor (brother, sister, or a compatible unrelated donor). Allogeneic transplantation provides a double effect: restoration of normal hematopoiesis and a "graft versus disease" effect.

Recovery is expected in 30-50% of patients with aggressive lymphomas undergoing myeloablative therapy. In indolent lymphomas, recovery from autologous transplantation is questionable, although remission may be achieved more frequently than with palliative therapy alone. The mortality rate of patients after the use of the myeloablative regimen ranges from 2 to 5% after autologous transplantation, and about 15% after allogeneic transplantation.

Consequences of standard and high-dose chemotherapy are secondary tumors, myelodysplasias, and acute myeloid leukemia. Chemotherapy combined with radiation therapy increases this risk, although the incidence of these complications does not exceed 3%.

Non-Hodgkin lymphoma prognosis

Patients with T-cell lymphoma generally have a worse prognosis than those with B-cell lymphomas, although new, intensive treatment programs are improving prognosis.

Survival also depends on many factors. The International Prognostic Index (IPI) is often used for aggressive lymphomas. It is based on 5 risk factors: age over 60, poor general status [by ECOG (Eastern Cooperative Oncology Group)], increased LDH, extranodal lesions, stage III or IV. Treatment effectiveness deteriorates with increasing number of risk factors; the actual survival rate also depends on the cell type of the tumor, for example, in large cell lymphoma, the 5-year survival rate in patients with 0 or 1 risk factor is 76%, while in patients with 4 or 5 risk factors it is only 26%. Usually, patients with\u003e 2 risk factors should receive more aggressive or experimental treatment. For indolent lymphomas, the Modified International Follicular Lymphoma Prognostic Index (FLIPI) is used.

It's important to know!

The diagnostic assessment of benign and malignant lymphoproliferative skin diseases is a very difficult task for the pathologist. In recent decades, significant progress has been made in this direction, associated with the success of immunology.