Follicular lymphoma 3a. Follicular lymphoma: symptoms, reasons, treatment

Follicular lymphoma is an indolent non-Hodgkin Lymphoma derived from the centrocytes and the centroblasts of the lymphatic assembly, manifested by a wave-like slow magnification and a decrease in the size of lymph nodes, the lack of pronounced clinical manifestations, a good response for treatment, but frequent relapses, as well as long-term overall survival.

In early classifications, this type of lymphoma was indicated as a histiocyte, centralocytarocitary, lymphoma of small or large cells with split nuclei, diffuse from small split cells, lymphoma from cells of follicular centers and several other names, for example, Brill-Simmems disease.

EPIDEMIOLOGY
Follicular lymphoma is the most frequently found indolent Nevhodazkinsky lymphoma (the second frequency of non-Khozkinsky lymphoma after diffuse B-laminating) in Europe and the United States, ranges from 20 to 35% in the group of non-goods-shop lymphatic lymph (in our country - there is much less often, there is no accurate data).

Men and women are sick about the same often, mainly over the age of 60. Patients of a white race are 2-3 times more often than the rest.

Morphology and immunophenotype
In the WHO classification, a single concept was introduced - follicular lymphoma, but three types (or gradations) are isolated, differing in the tumor substrate of large cells - centroblasts in the tumor substrate. With a follicular type I lymphoma in the field of view of a large increase in the microscope (x40), up to 5 centroblasts are detected; with a follicular type II lymphoma - from 6 to 15 centroblasts; With a follicular lymphoma of type III - more than 15 centroblasts, while type III is divided into two categories "A" - among blasts there are centcrocities, and "b" - blades cover all fields of view. Follicular lymphoma I, II and III of type clinical flows are classical indolent lymphomas, while follicular lymphoma IIIIB type (up to 10% of all follicular lymphomes) is distinguished by aggressive flow and is treated according to aggressive lymph programs.

Histologically detected almost complete replacement of the lymphatic node with tumor tissue, often spreading outside the capsule.

The tumor usually has a follicular or mixed follicular and diffuse structure, less often - only diffuse. Within one lymphatic node, follicles are similar in shape and sizes than differ from jet follicles with a benign hyperplasia of lymph nodes. There are more or less pronounced T-zone between follicles, which contains small lymphocytes and centrocytes - small angular cells, which are not normally detected outside lymphoid follicles. Tumor follicles are not surrounded by a layer of small lymphocytes - mantle zone.

The population of tumor cells consists of centroblasts and centrocytes. The centrocytes are cells, 1.5-2 times higher than the size of a small lymphocyte, with an angular core of an incorrect form, at which a groove or a trait is sometimes visible, due to which the kernel is called split. The core contains rough heterochromatin and is not always a distinguishable nucleoline. The rim of the cytoplasm is practically not visible.

Centroblasts are larger than the centrocytes, have a rounded shape and a distinct rim of basophilic cytoplasm. A distinctive histological feature of the follicular lymphoma are extensive sclerosis fields, mainly in visceral lymph nodes.

For follicular lymphoma, the expression of surface immunoglobulins is characterized (more often Igm) and Pan-B-cell markers CD19, CD20, CD22 and CD79A. Tumor cells of follicular lymphoma express the antigen of the germinal center, including CD10. Proliferating fraction (Ki-67-positive cells) is usually small - up to 3%. In some cases, the low-degree follicular lymphoma (LOW-GRADE) has a high Ki-67 proliferation index and is manifested by an aggressive clinical flow. The characteristic diagnostic sign of the follicular lymphoma is the expression of BCL-2 protein, which allows differentiable FL and follicular reactive hyperplasia of lymph nodes, under which the expression of BCL-2 protein is absent. In some cases, difficulties in the differentiation of follicular lymphoma are observed from other non-nodzhkinsky lymphomes, such as lymphoma of mantle cells, marginal zone lymphoma and lymphoplasemic lymphoma. In this case, tumor cells of the follicular lymphoma (I and II type) almost never express CD5 and extremely rare CD43. In rare cases, the follicular lymphoma can be CD10- or BCL2-.

Citogenetic and molecular genetic properties
In the diagnosis of follicular lymphoma, a molecular genetic analysis may be useful to determine the rearrangement of BCl2, cytogenetic analysis or FISH technique to determine the variant T (14; 18) or T (8; 14). In almost all cases of follicular lymphoma it is possible to detect cytogenetic disorders. Chromosomal translocation T (14; 18) (Q32; Q21) is a leading and occurs in 70-95% of cases of follicular lymphoma. As a result of this translocation, BCL-2 locus is connected to a variable jH segment of the transcriptional-active gene of severe μ-chain of immunoglobulins (IGH) located on the long shoulder of chromosome 14 in the Q32 band. As a result of such a translocation, these two genes are connected in such a way that their transcription goes in one direction, and BCL-2 is transcribed with the participation of the active industrial circuit gene promoter, which contributes to the hyperactivation of BCL-2. Such activation leads to hyperproduction of the protein product of the BCL-2 gene - oncoprotein BCL-2, a powerful apoptosis inhibitor.

However, the presence of translocation T (14; 18) is not a necessary condition for the accumulation of BCL-2 protein, since in most cases BCL-2 actively accumulates in the absence of this chromosomal restructuring. This confirms the presence of other BCL-2 activation paths. In young patients with a localized BCl2 - negative follicular lymphoma, a diagnosis of pediatric follicular lymphoma may be considered.

Other cytogenetic violations: Trisomy on chromosomes X, 3, 5, 7, 8, 9, 12, 17, 18, 20, 21, deletions 6Q23 and 6Q25-27, anomalies in XP22, 1P21-22, 1P36, 7Q32, 10Q23- 25 Translocation 3Q27 occurs in about 15% of cases of follicular lymphoma. As with other translocations affecting the K27 band of chromosome 3, in which the BCL-6 gene is located, the activity of this gene encoding the protein zinc-containing transcription factor is listed, which plays a significant role in the formation of embryonic centers of lymph nodes. This leads to the exit of the proliferation of the cell line of the embryonic center from under the suppressor control and the development of clonal expansion. Aberration involving the BCL-6 gene and another known oncogen MYC, as well as mutations of the proapopotic gene - P53 are predisposing molecular genetic events to the development of the large-milking transformation of follicular lymphoma. Follicular lymphoma with trisomy 3 and translocation 3Q27-29 is a high risk disease and refers to the subgroup of follicular lymphoma with marginal differentiation. The high-risk group of transformation also includes follicular lymphoma with plasmocyte differentiation ("plasma-like lymphoma").

CLINICAL MANIFESTATIONS
In most patients, follicular lymphoma is diagnosed in a common stage - only one third of patients have I or II stage at the time of the disease. In addition to lymphatic assemblies (peripheral and visceral), spleen and bone marrow are usually affected (up to 70% of cases), 10% of patients have lymphocytosis and tumor cells are found in peripheral blood. Less often affect the lymphatic structures of the rings of the holter and the extraudal areas: the gastrointestinal tract, soft fabrics, leather, and the follicular lemon lymphoma is one of the most frequent in-cell skin lymphomes.

The clinical course of the disease is characterized by progressive, often for several months or years, asymptomatic increase in lymph nodes, randomly detected by the doctor or the patient himself. B-symptoms are found no more than 10% of primary patients with follicular lymphoma and are most often detected in the later stages of the disease. At the same time, there is often a progression in the follicular lymphoma of type III. "Transformation" into an aggressive diffuse B-large-milking lymphoma (an increase in the proportion of centroblasts in a tumor substrate more than 50%) occurs in 22% of patients with follicular lymphoma I and II types during the first 5 years of the course of the disease. These patients are treated according to the programs of aggressive lymphoma, however, chemoriness is usually developing and the forecast is significantly deteriorating - the median survival from the moment of confirmation of the transformation is only 22 months.

Survey and staging
Initial clinical examination with the firstly detected follicular lymphoma should include a thorough physical examination with special attention to the size of lymph nodes, an assessment of general condition and constitutional symptoms.
Laboratory studies: general blood test with leukocyte formula, serum lactate dehydrogenase levels and serum β2 microglobulin. Testing to the hepatitis B virus (due to the increased risk of viral reactivation with the beginning of immunotherapy). In certain cases, measuring the level of uric acid, testing for the hepatitis C virus
To document the I or II clinical stage, it is necessary to eliminate the damage to the bone marrow. For this, it is shown to perform an adequate trepalobiopation (sample length ≥1.6 cm) together with the aspiration of the bone marrow. If further radioimmunotherapy is supposed, bilateral biopsy is recommended; In this case, the pathologist must provide the percentage of common cell elements and the percentage of affected cell elements. Bone marrow biopsy can be postponed if observation is assumed instead of active treatment.
In the case of the intended use of arresters with anthracycline or anthracendions, it is necessary to evaluate the function of cardiac output (echocardiography).
The staging of follicular lymphoma is carried out on the Ann Arbor system. To accurately detect tumor lesions, a computed tomography of a chest, abdominal cavity and a small pelvis is shown. CT-scan of the neck can help in the assessment of localized disease.

Positron-emission tomography - scanning is useful in primary patients with an allegedly localized disease to identify hidden foci or with suspected histological transformation. Positron-emission tomography does not replace histological confirmation of the diagnosis, however, the areas of increased activity of fluorideoxyglucose indicate the activity of fluorideoxyglucose with tumor lesion.

Prognostic systems
The international prognostic index for follicular lymphoma was developed in 2004 and is based on age, the stage on Ann Arbor, the number of injected nodal areas, hemoglobin levels and serum lactate dehydrogenases. FLIPI was developed on the basis of a large number of retrospective data on 4167 patients with follicular lymphoma collected between 1985 and 1992. All the test parameters were available in 1795 patients, on the basis of which three separate prognostic groups were revealed with a 5-year survival rate in the range from 52.5DO 90.6%.

The FLIPI prognostic index did not take into account the new information related to the widespread use of Rituximab, which currently became the standard of effective treatment in the first line of therapy, and also applies to relapses and the progressive course of follicular lymphoma. A new study was initiated by an international project to study prognostic factors in the follicular lymphoma in 2003 (Research F2). It was the result of an assessment of the treatment of 942 patients with follicular lymphoma in 69 European and American centers from 2003 to 2005. 826 patients received systemic therapy (559 - with Rituximab, 267 - without it).

The new FLIPI-2 index is based on the study of survival without progression, although it is also a powerful tool for determining the overall survival in the group of patients receiving rituximab. After analyzing 832 patients with full data, 5 risk factors were isolated, which were included in the FLIPI-2 model: an increased level of β2 microglobulin, the longest (maximum) diameter of the largest affected lymph node more than 6 cm, bone marrow damage, hemoglobin level of less than 120 g / l and age for over 60 years.

Further, since the data is available during the progression period, the survival rate without progression can be used instead of a general survival as a final point for research, which is important in clinical studies of indolent lymphoma. Survival without progression reflects tumor growth, it can be estimated earlier than the overall survival rate, and does not depend on subsequent therapy. In addition, the level of β2 microglobulin and the longest diameter of the largest affected lymphatic node used in the FLIPI-2 model reflecting the biological activity of the tumor volume of the tumor mass, respectively, can be easily measured. FLIPI-2 can also be useful for assessing the forecast in patients receiving active therapy with rituximab.

TREATMENT
The therapeutic strategy for follicular lymphoma should be based on a risk-adapted approach, taking into account the potential non-developability of the disease. In elderly patients over 60 years old without unfavorable forecast factors, the expected median survival is about 10 years, therefore the main goal of therapy of such patients is the quality of life, and not the quality of remission or survival. In young patients who have adverse prognostic factors, the median survival is less than 3 years, so the quality of remission for this group is more important. The quality of remission during follicular lymphoma, as with other types of non-Hodgkinsky lymphomas, is of great importance - in patients who managed to achieve complete remission, survival rates are higher compared to patients with partial response.

Treatment of patients with localized follicular lymphoma stages
Almost 15-25% of patients with follicular lymphoma are diagnosed in the initial stages (I and II). Due to the high radarity sensitivity of the follicular lymphoma and potentially, the standard therapeutic approach for such patients is radial therapy for primary zones involved, which allows to obtain a complete remission in 90-95% of cases, and 5-year-old uniodic survival reaches 60-70%.

The results of earlier studies with a long observation period demonstrated favorable outcomes in these patients. Among patients with the I-II stage of follicular lymphoma with a low degree of differentiation, which initially received radiation therapy for primary zones involved or large-scale radiation therapy, the median of the total survival was 14 years old; 15-year-old overall survival - 40% and 15-year survival without consequences are also about 40%. In these studies, the proportion of patients with the I stage of follicular lymphoma was 41%. The oscillations of 15-year survival without consequences were influenced by the stage of follicular lymphoma (66% at stage I vs. 26% at stage II) and the maximum tumor size (49% at a tumor 3 cm). The difference in overall survival was insignificant with large-scale radiation therapy compared with radiation therapy for primary zones involved (49 against 40%, respectively). According to a recent study by B. Campbell et al., In patients with limited stage of follicular lymphoma (types I-I-I-III, N \u003d 237), which received local (on primary zones) radiation therapy or limited local radiation therapy (only affected lymphatic Nodes), the decrease in the irradiation zone did not affect the frequency of survival without consequences and overall survival: 10-year survival without consequences and overall survival accounted for 49 and 66%, respectively.

The recurrence usually happens in areas that have not been ray influence, or in extracurne-far organs, which indicates the prevalence of the process by the time of diagnosis and incorrect staging when using traditional methods of examination. In addition, the results of the study of the efficiency of radiation therapy in patients with follicular lymphoma were obtained mainly before the use of rituximab.

Combined treatment, as it turned out, improves survival without progression, but does not affect the overall survival in patients at the early stage of follicular lymphoma. In a recent retrospective study, the outcomes of the treatment of 145 patients with the I - II stage of the follicular lymphoma, treated from 1967 to 2011, were estimated with various approaches in the first line - from "Watch and Wait" to chemotherapy, radiation therapy, a combination of radiation therapy + chemotherapy, monotherapy Rituximab, chemoimmunotherapy. No significant difference was detected in 7.5-year-old survival (66% - with radiation therapy, 74% - during chemotherapy, 67% - with radiation therapy with chemotherapy, 72% - when observed, 74% in chemoimmunotherapy).

In a prospective study on the basis of data National Lympho Care, the outcomes of various approaches of therapy of the first line in patients (n \u003d 206) with the I stage of follicular lymphoma are evaluated. These approaches included: "Watch and wait" - 17%, only radiation therapy - 27%, rituximab monotherapy - 12%, rituximab + chemotherapy (chemo-impaired heating therapy) - 28%, combination with radiation therapy (usually chemimmunotherapy with subsequent radiation therapy) - 13 %. In the median of observation of 57 months, the median survival without progression after radiation therapy was 72 months; The median survival without progression was not achieved at other approaches.

At the same time, as before, at different approaches, there were no significant differences in the frequency of general survival. The feature of the study was that these patients were strictly stared (including a bone marrow study, computed tomography and or orpositron-emission tomography), and they could have an advantage of systemic therapy, unlike other 265 patients with this study, which have a median survival without The consequences were worse. It is not excluded that the standard approach to the treatment of early stages of symptomatic follicular lymphoma with only radiation therapy can be changed in the near future therapeutic strategies aimed at systemic therapy. Of course hopes are imposed on the positron-emission tomography, the widespread dissemination of which will make it possible to more accurately distribute patients into groups with local and common defeat. The advantage of combined chemical treatment for improving the overall survival in patients with localized stages, according to available data, has not yet been reliably proven, but there are currently research on this topic. This is especially true for a group of patients with a large local tumor mass or with several affected areas. It is in this group of patients who are often observed relapses in early terms after radiation therapy, so in some centers the treatment of such patients start with chemotherapy, in accordance with treatment approaches in generalized stages of the disease.

Indications for the start of system therapy
The criteria for the start of treating patients with the active flow of follicular lymphoma were proposed on the basis of clinical randomized studies before the wide range of therapy Rituximab and testified that the immediate start of treatment does not increase the results of survival compared to the tactics of "watching and waiting". At the same time, the presence of certain signs of activity of follicular lymphoma requires immediate start of therapy even at localized stages.

The most famous criteria for follicular lymphoma activity are offered by French researchers in 1997:
Signs of a large tumor mass - a tumor of more than 7 cm in diameter, more than two increased lymph nodes in three different areas, each more than 3 cm in diameter, symptomatic splenomegalia (more than 16 cm on computed tomography), organ compression (in epidural space, ureterals, etc. .), Ascites or pleural effusion;
cytopenia (leukocytes less than 1x109 / l and / or platelets less than 100x109 / l);
leukemization (more than 5x109 / l of tumor cells);
system manifestations (ECOG-WHO status more than 1);
Improving the level of serum lactate dehydrogenase or β2 microglobulin.

British criteria had a similar set and among others also included quick generalization of the disease (for 3 months), bone marrow damage, and Italian - an extremeal defeat of more than 7 cm. New indications about the need to start systemic therapy, taking into account the use of rituximab and other modern drugs will be based on the results of clinical studies.

Selection of therapy with limited stages of follicular lymphoma (stage II)
Currently, patients with confirmed I or II stage of follicular lymphoma, a preferred treatment option is radiation therapy for primary zones involved (24-30 gr, +6 GR is additionally for patients with a large tumor mass). In some cases, when the toxicity of local radiation therapy outweighs potential clinical benefits, a suitable option may be observation. Alternative approaches include "watching and waiting", immunotherapy with or without chemotherapy, with or without radiation therapy. For patients with partial response after primary treatment of immunotherapy with or without chemotherapy (but without radiation therapy), it is necessary to consider as an additional treatment of radiation therapy for primary zones involved (local).

Patients with partial response (after local radiation therapy) or with a full response are subject to observation every 3-6 months during the first 5 years, and then each year (or by clinical indications). Computer tomography is carried out no more than every 6 months during the first 2 years after the complete completion of therapy, and then no more than once a year (or by clinical indications). Patients who have not reached the response to the first line of therapy are subject to the same treatment as patients with an advanced stage of the disease.

Approaches for generalized stages of follicular lymphoma (including II stage with a large tumor mass)
The problem of treating patients with follicular lymphomas with generalized stages is currently not solved. The main question of the need to immediately start treating patients with asymptomatic flow, especially the older age category. Patients with advanced follicular lymphoma stages should begin treatment only in the presence of testimony that the most fully take into account the Gelf's criteria. To begin treatment, the signs of sustainable progression of the disease are also important for more than 6 months, the involvement of extroduction foci, other life-threatening symptoms with the defeat of individual bodies.

Currently, some patients are focused on the immediate start of treatment, even in the absence of clinical indications. Such patients should be part of participation in relevant clinical studies. The results of the study of monotherapy rituximab in asymptomatic patients with common stages of follicular lymphoma, which indicate that such therapy can significantly delay the need to start new therapy. Thus, 462 patients with follicular lymphoma of I-sha types and II-IV stages of the disease (without a large tumor mass) were randomically divided into 3 groups.

In the group A, observation was carried out, the group B received rituximab in 375 mg / m2 weekly No. 4, and the group C was treated in the same way as the group B followed by the supporting therapy Rituximab every 2 months for two years. In the process of observing 20% \u200b\u200bof patients, new therapy was required. In 3% of patients from the Group A, spontaneous remissions are marked, in 6% - partial response, the disease remained without changes (74%), and progression is noted in 17%. At the same time, the median before the start of therapy was 33 months, as previously noted by other researchers.

In the group, 45% of complete and complete unconfirmed remissions, 33% of partial remissions were noted, in 19% there were no changes, and in 3% progression. The group with the results were a bit, but insignificantly better than in the group B. However, the time before the start of the new therapy in the groups received by Rituximab, was significantly increased compared to the observation team, and the median for 4 years was not achieved. Thus, taking into account the existing evidence of the effectiveness of the active approach to treatment, the popular approach "Watch and Wait" is now time to change on at least "Watch and Worry" ("Watch and Relax").

When choosing the initial line of therapy, unnecessary myelotoxic modes in patients who subsequently may be candidates for highly visible chemotherapy with AUTO-TGSC.

In some cases, elderly and weakened patients who cannot transfer chemotherapy, with a palliative purpose possible use of local radiation therapy. Asymptomatic patients, especially 70 years old, are mainly subject to observation.

First line of immunochemotherapy
Monotherapy with chlorambucil or fludarabin does not affect the overall survival, and in the treatment of patients with follicular lymphoma with advanced stages does not apply. At the same time, Fludarabine causes a significant myelosuppression and immunosuppression, and also worsens the opportunity to assemble blood stem cells from candidates for outologue transplantation.

Cyclophosphamide as a monotherapy in the CALGB study demonstrated the same overall survival and a complete response, as well as cyclophosphamide-containing combined chemotherapy Snor with bleomycin, but in the subgroup of these patients who had only mixed phenotype (N \u003d 46), a tendency to improve the results of combination therapy was noted . Interferon Alpha was actively used to treat indolent lymphomas, including follicular lymphoma, since the early 1980s. Remote results showed that the presence of interferon in the composition of induction therapy does not affect the frequency of response and on overall survival. Given the sufficiently high toxicity of interferon with long-term use and significant deterioration in the quality of life of patients, this drug is not used in the treatment of follicular lymphoma and other lymphoproliferative diseases.

Rituximab in monotherapy can be applicable in elderly or weakened patients, however, data on its effect on overall survival in this mode is missing. Polyza from adding rituximab in combination with chop or in increasing the response rate, time before progression or overall survival of all patients with advanced stages Follicular lymphoma is proved in several randomized studies.

W. Hiddemann et al. showed a statistically significant advantage of R-chop (n \u003d 223) against chop (n \u003d 205) when studying 2-year-old survival (95% against 90%). M. Herold et al. When studying the effectiveness of the MSR combination (mitoxantrone, chlorambucil and prednisone) with rituximab (R-MCP; N \u003d 181) against MSR (n \u003d 177), an increase in 4-year-old survival rate was demonstrated: 87 against 74%. Almost simultaneously R. MARCUS et al. They revealed the advantage (n \u003d 159) over (n \u003d 162) in an increase in the 4-year-old s virtually identical results: 83 against 77%.

When studying the combination of fludarabine, cyclophosphamide and rituximab in the first line of therapy in primary patients with follicular lymphoma (n \u003d 75), Spanish researchers J. Tomas et al., Despite the high efficiency of this scheme (89% of full responses), revealed high mortality associated with With treatment (n \u003d 10), in connection with which the FCR mode is not recommended in the first line of FL therapy. In Italian study, FOLL05 (N \u003d 534), R-CVP, R-CHOP and R-FM are compared in the treatment of primary patients with II-IV stages of follicular lymphoma. It has been established that R-CVP was associated with a reduced 3-year survival rate to progression (47%) compared to R-FM (60%) and R-CHOP (57%). At the same time, R-chop showed anti -olimphoma activity similar to R-FM, but a significantly better toxicity profile, so it can be considered at the present time as a standard mode in the treatment of patients with advanced follicular lymphoma stages.

Recently M. Rummel et al. We demonstrated that Br (Bandamustine and Rituximab) mode contributes to better survival without progression and less toxicity compared to R-chop. In the study, in addition to patients with follicular lymphoma, patients with other indolent lymphomas and lymphoma of mantle cells were participated, and 514 patients were randomized: 274 (estimated 261) for treatment under the program BR and 275 (253 rated) - on R-chop. The median survival without progression was significantly higher on the program BR (69.5 months) than on R-CHOP (31.2 months). At the same time, for patients with follicular lymphoma (n \u003d 279), the median survival without failure is not achieved in the treatment under the program BR (against 41 months with therapy R-chop, p \u003d 0.0072).

Patients with follicular lymphoma, which have reached a partial or complete response to the first line of therapy, can later or be observed, or obtain supporting therapy. Previously, attempts were made to apply Interferon Alpha for supporting treatment, but the safety profile and the tolerability of this drug did not assume its long-term use in this category of patients.

In 2013, the results of the PRIMA study results were published after 6-year observation, in which 1217 patients participated. After the first line of therapy, 1019 patients achieved complete or partial remission. Of these, 505 patients were supported by rituximab (375 mg / m2 every 8 weeks) to 2 years, and in the second group (n \u003d 513) - observation. With a median of observation of 73 months in a group of supporting therapy, rituximab 6-year-old uniodic survival accounted for 59.2%, and in the observation group - 42.7% (p \u003d 0.0001). At the same time, the overall survival was not significantly different, including according to meta-analysis 9 studies (N \u003d 2586), published in 2011, which is perhaps due to the need for longer observation in order to demonstrate a statistical difference in survival rate. Nevertheless, 2-year-old supporting therapy Rituximab after successful chemotherapy with rituximab has become a new standard for the treatment of the first line for patients with common stages of follicular lymphoma.

In addition, due to the fact that rituximab does not damage stem hematopoietic cells, the drug can be used before harvesting. As studies are shown, rituximab really makes it possible to reduce the contamination of autotransplant with tumor cells and increases the frequency of molecular remissions after conducting highly visible chemotherapy, without extending the period of recovery of hematopois after transplantation.

Due to the advent of the subcutaneous form of rituximab, the ability to carry out supporting therapy in follicular lymphoma are expanding. A new variant of alternative supporting therapy in the first remission of follicular lymphoma can be radioimmunotherapy (for patients without substantial involvement of bone marrow).

Patients receiving supporting therapy rituximab are observed every 3-6 months during the first 5 years, and then each year (or by clinical indications). The CT scan is performed more than every 6 months during the first 2 years after the complete completion of therapy, and then no more than once a year (or by clinical indications). The value of the study of positron-emission therapy with follicular lymphoma is significantly lower than with diffuse B-large cell lymphoma.

Follicular lymphoma refers to the type of cancer, but in contrast to other types of similar lesions, has a less aggressive current. The diagnosis is set in rare cases. Patients after therapy are usually given disability.

general information

The follicular type is diagnosed in each third case when establishing lymphoma in adults. In children and patients under the age of 30 years, such a disease is detected in rare cases.

Often, such a diagnosis as follicular lymphoma is detected in men from 60 years. The risk group also includes people suffering from immune diseases of a congenital character.

The neoplasms are formed from B-lymphocytes and are formed in the follicular center of the lymphatic node. They are localized in larynx, almonds, stomach, spleen. Thus, the pathological focus may occur in any part of the body.

Modern medicine cannot help achieve full cure. Even after the course of therapy, the disease returns after 3-5 years.

Classification

Depending on the structure of the neoplascence, three main forms of lymphoma are isolated: follicular, diffuse and follicular diffuse. Each of them has a number of features.

Follicular lymphoma is also divided into several subspecies depending on the mechanism of development.

Nevhodknaya

The formation of a follicular nehodgkin lymphoma comes from the V- and T-cells of immunity. At the initial stage, the defeat affects only one lymphatic node. Over time, the pathological process applies to the rest.

The focus can be located in the bone marrow or the mucous membrane of the lymph node.

In cell lymphoma

It is considered the most common type of disease. Most often is installed in a large-cell lymphoma. Also, this type includes small-cell, berkitta, mediastinal formation, and coolery leukemia.

B-cell lymphoma is quite aggressive type and is characterized by rapid growth. In the absence of timely therapy, the likelihood of complete disposal of the disease is reduced.

Second Cytological Lymphoma

The structure of the neoplasm is practically no different. To accurately determine their type, experts are distinguished by cytological and histological type.

As education develops, its type can change. The cytological type lymphoma is distinguished by an aggressive flow, rapidly grow. Unpleasant symptoms appear already at the initial stages of the development of the disease.

Treatment is carried out only complex. To achieve positive results, maximum doses of chemotherapeutic preparations are used.

Third cytological lymphoma

The formation of this type has the most unfavorable forecast. This is due to the fact that the risk of repeated development of the disease is quite high even after the course of chemotherapy and operational intervention in the bone marrow transplantation.

The forecast is possible to improve the help of special drugs. But they can also not give one hundred percent result.

Causes

Lymphoma is a cancer in which the pathological process affects the lymphatic system. The reasons for its development did not establish specialists.

The studies have made it possible to identify a number of factors that influence the body and significantly increase the risk of developing pathology. It is also believed that the occurrence of lymphoma is associated with chromosomal anomaly.

As additional factors, other genetic deviations are distinguished, contact with poisonous, chemical and toxic substances.

The bad habits that the patient suffers from particular importance. These include smoking and drinking alcohol. The composition of alcohol and tobacco smoke contain carcinogenic substances, negatively affecting the body's state.

Also, experts believe that the fundamental factors are ionizing radiation, the application for a long time of antidepressants, the presence of autoimmune diseases and accommodation in the area with an unfavorable ecology.

Symptoms of follicular lymphoma

The disease is dangerous in that in the first and second stage it can flow without visible signs. Patients do not complain about worsening well-being, there is no discomfort. Symptoms are manifested when the pathological process affects the bone marrow.

As the disease develops, there is an increase in lymph nodes located in the neck, the axillary depression and the groin zone. They become painful, especially when palpation.

At night, an increased sweating occurs, weakness appears, fast fatigue, the body hyperthermia is observed. In cases where the pathological process affects the spleen, the body increases. The difficulty of the swallowing process is manifested when almond cells affect the almonds.

When conducting diagnostics, anemia is established. At the fourth stage of development of the disease, the neurological system is defeated, which is accompanied by appropriate features.

Diagnostic methods

In order to establish a faithful diagnosis, a specialist conducts comprehensive diagnostics. In suspected lymphoma, primarily the doctor examines the patient's history in order to identify possible causes.

To get a complete picture of the disease, laboratory tests and instrumental diagnostic methods are prescribed.

Inspection

When conducting an oncologist's procedure also carries out a palpator study of lymphatic nodes.

But not all types of formations can be determined using a similar procedure.

Biopsy

With the help of a thin-game biopsy, the affected fabrics of the lymphatic node are taken. The materials obtained are sent to the laboratory for a cytological study.

The technique allows you to establish the degree of malignancy and the prevalence of the pathological process. The procedure is performed under anesthesia, as it is sufficiently painful.

Laparoscopy

The procedure is applied not only for treating purposes, but also for diagnosis. It is used for a comprehensive study of the abdominal organs.

Laparoscopy allows you to estimate the degree of prevalence of the pathological process, damage to organs.

Bone marrow puncture

The procedure has sufficiently high informativeness and is assigned to establish the presence of metastatic lesions.

Puncture allows reliable data and a complete picture of the disease.

Cytogenetic

Laboratory study aimed at studying chromosomes. The technique allows you to establish a link between the cellular structure and heredity.

With the help of cytogenetic research, experts can explore the structure of the cell core.

X-ray study

Using X-ray, it is possible to determine the area of \u200b\u200bdamage and localization of the focus of the pathological process.

The procedure is painless and practically does not have contraindications.

Ultrasound

Patients are prescribed an ultrasound study of the thyroid and mammary glands, lymph nodes, internal organs.

Ultrasound allows you to determine the violation of the health of the liver, spleen and other organs, determine the degree of their increase.

CT or MRI

With the help of layer-by-layer scan, a specialist manages to determine changes in the chest area.

Computer and magnetic resonance imaging are carried out to establish structural disorders, even if the lesion is small.

As additional diagnostic methods, patients prescribe lymphoscintigraphy, internal organs and bone scintigraphy.

Based on the results obtained, the specialist establishes the diagnosis and determines the course of therapy.

Treatment

When establishing follicular lymphoma, the course of therapy is assigned individually. It is important to remember that the earlier the patient appealed to the oncologist, the higher the chances of recovery.

It is important that the specialist regularly conducts surveys, especially when setting 1-2 types of follicular lymphoma, when the pathological process proceeds slowly.

The fatal outcome in the early stages at properly conducted therapy occurs only in exceptional cases.

When lymphoma is diagnosed, having rapid development and accompanied by a number of unpleasant signs, treatment is carried out immediately. Patients may assign chemotherapy or laser therapy.

If metastatic lesions are observed in the bone marrow, surgical intervention is appointed, the purpose of which is the body transplantation. At the same time, the period of remission is short.

Metastases arise in remote organs already at 4 stages of development of pathology. Chemotherapy or laser therapy are used to improve the patient's well-being and deceleration. Mandatory assigns therapy to maintain immunity.

In some cases, secondary leukemia is installed as a concomitant disease. In this case, the pathological process affects the bone marrow. Experts use the transplantation of affected areas.

To date, the technique of snar is popular in the treatment of pathology. Oncologist appoints a number of drugs. The course of therapy implies the use of "cyclophosphane", "Winskrestin", "prednisolone" and "doxorubcin".

In individual clinics, new experimental treatments are applied. But an important stage is the timely appeal to the oncologist.

Disability

Follicular lymphoma is a dangerous disease that is seriously treating even at the initial stages of its development.

Depending on the stage of the formation of the pathological process, the presence of complications and the results of therapy of the patient is established a certain group of disabilities. The third is determined if there are 1 or 2 stages. The second group of disability is given if there are 2 and 3 stages.

The first group is determined in accordance with the third or fourth stage in the development of the disease.

Possible complications

Follicular lymphoma as the pathological process spread the complications causes complications.

As ulcers are formed on the mucous membrane of the internal organs. After even minor physical exertion, fatigue occurs.

Patients complain about hair loss, frequent bleeding are observed, blood coagulation indicators deteriorate. Against the background of the development of the disease, immunity is reduced, as a result of which the body becomes infectious defeats.

Also noted a decrease in body weight and degradation of appetite. But the most dangerous consequence of follicular lymphoma is the distribution of metastatic lesions. As they have been developed, even when conducting therapy in a short time, the fatal outcome comes.

In addition, the decay of the formed formations is possible, as a result of which the kidney performance, the cardiovascular and nervous system is disturbed.

Even after successful treatment, there is a retest of pathology after 3-5 years. That is why treatment should be carried out in a timely manner and regularly attend the doctor with the aim of preventive inspections.

Forecast

Depending on the degree of prevalence of the pathological process, the state and age of the patient, the presence of concomitant diseases establishes the forecast.

When the disease has 1 or 2 stage, it is possible to achieve continuous remission. Survival of patients when follicular lymphoma, regardless of its type, has 3 development stage, is about 50%.

In 4 stages, metastatic lesions are affected by not only neighboring fabrics, but also penetrate into remote organs. At the same time, the forecast is unfavorable. Conducting treatment allows only to facilitate the suffering of the patient and extend his life.

In case of severe flow, the fatal outcome occurs as a result of the development of complications under which there is a violation of the performance of many organs and systems. At 4 stages of follicular lymphoma, survival rate is about 10%.

Prevention

In order to reduce the risk of developing disease, patients are recommended to adhere to the following prophylaxions:

1. News healthy Lifestyle.
2. Refuse such harmful habits Like smoking and drinking alcoholic beverages.
3. Correctly feed The diet must be balanced. The menu must include vegetables and fruits, as they contain a sufficient number of trace elements and vitamins.
4. Support immunity. During the peak period, the specialists recommend taking multivitamin complexes.
5. In case infectious Diseases in a timely manner and fully treated. It should not stop the reception of the prescribed drugs ahead of time, even if the well-being improved significantly, and the symptoms disappeared.
6. Exclude precooling organism and overheating.
7. Do not be for a long time on the sun. Sunny weather should be used by special protective creams. It is important to abandon the visit to Solariyev.
8. Observe the mode labor and rest.
9. Avoid significant physical and mental loads.
10. Exclude hypodynamine. To do this, you need to lead an active lifestyle.
11. If possible, avoid stressive situations, neurosis and depression.
12. Take up one year preventive inspections.

Compliant with the prevention rules are necessary not only in order to reduce the risk of developing pathology, but also after treatment. These recommendations will eliminate the re-emergence of pathology.

Follicular lymphoma is a dangerous disease, diagnose which in the initial stages is quite difficult. The danger of the disease is that even after the treatment occurs, relapse arises.

That is why patients are important to regularly visit the doctor and undergo preventive inspections. Only timely treatment and constant control will eliminate the emergence of serious consequences.

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The site provides reference information solely to familiarize yourself. Diagnosis and treatment of diseases must be under the supervision of a specialist. All drugs have contraindications. Consultation of a specialist is obligatory!

What is lymphoma?

Lymphoma - This is the disease, which is based on the defeat of the lymphatic system. To better present the nature of this pathology, you should familiarize yourself with the characteristics of the structure and the function of the lymphatic system.

The structure and functions of the lymphatic system

The lymphatic system consists of vessels that form a single network, permeating all internal organs. On this network, a colorless liquid flows, which is called lymph. One of the main components of lymphs are lymphocytes - cells that produce the immune system. Another link of the lymphatic system are lymphatic nodes ( lymph nodes), which consist of lymphoid tissue. Limphocytes are formed in lymph nodes. All links of the lymphatic system - lymph nodes, vessels, lymph perform a number of important functions necessary for human vital activity.

The lymphatic system performs the following functions:

• Barrier. In the lymph, in addition to lymphocytes, various pathogenic bacteria may be present, dead cells, foreign elements for the body. The lymphatic assembly plays the role of a depot, which cleans lymph, delaying all pathogenic particles.
• Transport. Lymph delivers nutrients from the intestines to the tissues and organs. In addition, this lymph is transported from the tissues of the intercellular fluid, due to which the tissue drainage is carried out.
• Immune. Lymphocytes that produce lymph nodes are the main "instrument" of the immune system in the fight against viruses and bacteria. They attack any harmful cells that detect. It is due to the fact that pathogenic microorganisms accumulate in lymph nodes, they increase with many diseases.

What happens to the lymph system during lymphoma?

In the lymphoma, the uncontrolled division of lymphatic cells begins, the accumulation of which forms tumor neoplasms. In other words, lymphoma is a tumor formed by a lymphoid fabric that can be in a lymph node or in any organ where there are lymphatic vessels. Type of tumors ( building, location), dynamics ( rising speed) And other characteristics depend on the variety of the disease.

Lymphoma is a cancer or not?

Lymphoma is a malignant neoplasm that people are denoted as "cancer". However, the lymphoma is very different between themselves, and, first of all, according to the degree of malignancy.

Causes of lymphoma

To date, one specific factor is not allocated to this day, which it can be said that it is the cause of lymphoma. But in history ( history of the disease) Patients with this pathology are often present similar circumstances. This allows us to conclude that there are a number of predisposing conditions that are not the truth cause of lymphoma, but create a favorable environment for the development and progression of this disease.

The following distinguishing towards lymphoma are distinguished:

• age, sexuality;
• viral diseases;
• bacterial infections;
• chemical factor;
• reception of immunosuppressants.

Age and sexuality

With age, the functionality of some organs is disturbed, which creates conditions that contribute to the occurrence of lymphoma. The risk group includes people aged 55 to 60 years. It should be noted that among patients with this disease are also faces under the age of 35 and even children. But the percentage of such patients is significantly lower than the elderly. Sexuality is important for Hodgkin lymphoma ( disease variation), Because among men this disease is diagnosed more often.

Viral diseases

Various viral and bacterial agents often act as a concomitant factor lymphoma. So, in many patients with the lesion of the lymphatic system, the Epstein-Barr virus is found. Penetrating the organism of air-drip ( for example, when kisses) or contact-domestic ( with touches, the use of things infected person) By, this virus causes various diseases. In addition to lymphoma, Epstein-Barr virus can provoke mononucleosis ( disease of mucus producing organs), hepatitis ( inflammation of the liver), multiple sclerosis ( brain disease).

The disease is manifested by symptoms that are similar for many infections, namely, a general discomplication, increased fatigue, increasing temperature. 5 - 7 days after infection, the patient increases lymphatic nodes ( in the neck, lower jaw, pah) And the rash appears, which can be in the form of points, bubbles, small hemorrhages. Other viral diseases that have a lymphoma occurrence are immunodeficiency virus ( HIV), some types of herpes viruses, hepatitis C virus

Bacterial infections

In addition to viruses, bacteria play some role in the development of lymphoma. So, it is noted that in patients with the stomach lymphoma diagnosed infection, the causative agent of which is the bacterium Helicobacter Pilori ( latin name - Helicobacter pylori). This microorganism dwells on the gastric mucosa or duodenum, causing various disorders from the digestion system. Interestingly, no other microorganisms, in addition to this bacteria, are not able to withstand the action of hydrochloric acid present in the stomach. Symptoms of infection Helicobacter Pilori are not a passing feeling of nausea, belching with a smell of rotten eggs, stool disturbances in the form of constipation or diarrhea.

Chemical factor

Under a chemical factor, various substances with a poisoning effect, with whom a person has been faced with a long time at work or in everyday life. Increased risk are subject to persons employed in the field of agriculture and in contact with pesticides. In people working in laboratories and in other areas associated with the use of various chemicals ( solvents, varnishes, benzene), also more often than the rest, lymphoma is diagnosed.

Reception of immunosuppressants

Immunosuppressants are a category of drugs that brake the activity of the immune system. Such drugs are prescribed to patients with autoimmune diseases ( pathologies under which the immune system begins to "attack" its own body). An example of such a disease can be red lupus ( multiple inflammatory processes affecting the skin, bones, internal organs), rheumatoid arthritis ( inflammation of the joints with their subsequent destruction).

Symptoms of lymphoma

The lymphoma is manifested by a number of signs, among which there are both characteristic features and characteristic of other diseases of the symptoms. Timely diagnosis and start of treatment is an important factor that ensures successful fighting tumor. Therefore, people, especially those who enters the risk group ( persons of the appropriate age, for example), Symptoms of lymphoma should be known to consult a doctor in time.

Symptoms of lymphoma are:

• increased lymph nodes;
• increased temperature;

• reinforced sweating;
• pain;
• other signs.

Three important symptoms in any form of lymphoma are elevated temperature, reinforced sweating and weight loss. If all of the listed features are present in history, the tumor is indicated by the letter B. In case there are no symptoms, the lymphoma is labeled by the letter A.

Increased lymph nodes during lymphoma

An increase in lymph nodes is the main symptom of this disease, which appears in the early stages. This is due to the fact that uncontrolled cell division begins in lymph nodes, that is, a tumor is formed. There are increased lymph nodes in 90 percent of patients with lymphoma.

Localization of increased lymph nodes
The lymph nodes located in the neck area and on the back of the neck increase more often during lymphoma. Often, the swelling of lymph nodes is celebrated in the axillary zone, next to the clavicle, in the groin. When the Khodkhan lymphoma, the swelling of the cervical or subclavian lymph nodes occurs approximately 75 percent of patients. An increase in lymph nodes can occur in one particular zone ( for example, only on the neck) or simultaneously in several places ( in groin and on the back).

Exterior of increased lymph nodes
With lymphoma, lymphatic nodes change to such an extent that if they are not covered with clothing, then rush. During palpation, a more dense consistency of affected lymph nodes is noted. They are mobile and, as a rule, are not laughing with leather and surrounding tissues. With the progression of the disease, enlarged nodes nearby are connected, forming large formations.

Whether lymph nodes are sick with lymphoma
Both enhanced and the remaining lymph nodes are not hurt at this disease, even with moderate pressing. Some patients have pain in the affected lymph nodes after drinking alcohol. Sometimes patients in the initial stages believe that lymph nodes increase due to the inflammatory process and begin to take antibiotics and other drugs against infection. Such actions do not cause results, since the tumor-like formations of this type do not react to anti-inflammatory drugs.

Increased temperature in lymphoma

Increased body temperature without visible external reasons ( colds, intoxication) It is a frequent "satellite" of almost all forms of lymphoma. In the initial stages of the disease, patients note a minor increase in this indicator ( as a rule, not higher than 38 degrees). This condition is called subfebilitation or subfebrile temperature. Subfebrile preserves a long time ( months) And does not disappear after the reception of drugs intended to reduce the temperature.

In the later stages of the disease, temperatures may increase to 39 degrees, when many internal organs are involved in the tumor process. Due to the tumors of the body system begin to function worse, which leads to inflammatory processes, as a result of which the body temperature increases.

Increased sweating during lymphoma

Increased sweating is a sign that is characterized by more for patients with Hodgkin's lymphoma. The sweating is intensified at night and in some patients it is so intense that the lower and even bed linen rolls. In medical practice, this feature is also called profuse ( that is very strong) Potting or night sweats. Pot does not have any pronounced odor or color.

Weight loss

Slimming without increasing physical exertion is a symptom characteristic of many forms of lymphoma. This contributes to the violation of metabolic processes, which provokes the tumor process. Often the disease, especially with the defeat of the organs of the abdominal region, is accompanied by a deterioration in appetite, nausea, vomiting, a feeling of crowded stomach. As a result, a person is rapidly losing weight, and in the later stages in some patients there is a strong, life-threatening exhaustion.

Pain in lymphoma

The pain syndrome is sometimes found among patients, but is not characteristic of the disease symptom. In other words, some patients may experience painful sensations in one or several parts of the body, other patients - no. The nature and localization of pain can be different. The presence of pain or their absence, their type and localization - all these factors depend on the organ in which the tumor is located.

In the lymphoma pain most often localized in the following organs:

• Head. Headaches are characteristic of patients who have lymphoma affects the back or brain. The cause of painful sensations is the disturbed blood supply to these organs, since the lymphoma squeezes blood vessels, preventing normal blood circulation.
• Back. The patients who are affected by the brain are affected by the pain in the back. As a rule, discomfort in the back is accompanied by both headaches.
• Chest. The pain in this part of the body is present in cases where organs in the chest are affected. By increasing in size, lymphoma begins to put pressure on neighboring bodies, because of what pain arises.
• Stomach. Pains in the abdomen are experiencing patients with lymphoma abdominal cavity.

Itching during lymphoma

The sebum itch is a sign that is characterized by more for the limphoma of Hodgkin ( occurs about one third of patients). In some patients, this symptom is preserved even after reaching remission ( symptom sinks). Itching can be local ( in one part of the body) or generalized ( throughout the body). At the initial stages of patient disease, local itching is concerned about the lower body, namely on hips, caviar. Subsequently, local itch flows into generalized form.
The intensity of this feature may be different. Some patients note a light itching, other patients complain about an unbearable feeling of burning, because of which they combed the skin, sometimes before the blood. Itching during the lymphoma subsides in the daytime and enhanced at night.

The feeling of itching with this disease is characteristic, but not constant symptom. That is, it can disappear or becomes not so strong and then appear to re-or enhance. In some patients, the attenuation of the itch can be a consequence of the positive reaction of the body on the therapy conducted, in the other patients it happens without the reasons for that.

Weakness in lymphoma

Weakness is celebrated by almost all patients with lymphoma from the initial stages of disease. Due to the fact that such a state is common and is not necessarily a sign of any disease, most patients do not give it due value. Weakness is noted in all muscles of the body and is not a consequence of physical overwork, but appears without obvious external reasons. This symptom is also accompanied by a decrease in working capacity and increased fatigue. Some patients complain of increased drowsiness, apathy ( loss of interest in everything).

Specific signs of lymphoma

This group includes those symptoms that are characteristic only for certain types of lymphoma. These features appear later than general symptoms ( temperatures, increased lymph nodes) and their occurrence is associated with the negative effect of the tumor on neighboring organs or tissues.

The following specific symptoms of lymphoma are exist:

• Cough. This feature appears in patients with a lymphoma located in the chest. The cough itself can be described as dry and exhausted. Traditional cough preparations do not bring significant improvement to patients. Accompanied coughing shortness of breath and chest pain.
• Edema. The swelling is a consequence of the impaired blood circulation, which happens when the lymphoma increases in size and begins to put pressure on the blood vessels. They swell those bodies that are near the tumor. For example, in the lymphoma, one or both legs swell into the groin.
• Digestion disorder. With damage to the lymphatic tissue, located in the abdominal cavity area, patients are worried about abdominal pain, diarrhea or constipation, feeling of nausea. Many worsen appetite and rapid false saturation occurs.

Types of lymphoma in humans

In modern medicine there are more than 30 varieties of lymphoma. The neoplasms differ in structure, sizes and other factors. Since the tumor is in the lymph node, and they are located in different zones of the body, then its location includes the distinctive criteria for lymphoma.
All existing lymphomas are divided into 2 large categories - Hodgkin lymphoma and non-Hodgkinsky lymphoma.

Lymphoma Hodgkin

Hodgkin lymphoma ( the second name is lymphogranulomatosis) Is a malignant tumor that affects the lymphatic system.
For this type of lymphoma, the formation of specific granulomas is characterized, from where the name of the disease follows. The main difference of this tumor from the non-Hodgkinsky lymphoma is the presence of special pathological cells in lymphatic tissue, which are called Reed-Sternberg cells. These cells are the main morphological characteristic of the Hodgkin lymphoma. These are large ( up to 20 microns) Cells containing several cores. The presence of such cells in Point ( content extracted by puncture) The lymph node is the main proof of the diagnosis. In view of the presence of these cells, the treatment of Hodgkin's lymphoma is fundamentally different from therapy, which is shown to patients with lymphosarcoma. Hodgkin's lymphoma is not as often as non-Hodgkin's lymphoma, and amounts to about 5 - 7 percent in the structure of all cancer and 35 to 40 percent in the structure of malignant lymphoma. Most often, this pathology is diagnosed in patients aged from 20 to 30 years.

The origin of the Hodgkin lymphoma cells is still unclear, but it is established that they are developing from in lymphocytes. There are many varieties of lymphoma based on the histological structure, but they are clinically much different with each other. As it was already said, fortunately Hodgkin's lymphoma is found not so often. Men is predominantly suffering from it. There are two peaks of morbidity - the first at 25 to 30 years, the second in 50 - 55 years. In young children, lymphoma is very rare. There is a genetic predisposition to the lymphoma. So, in twins the frequency of occurrence is 5 times higher than among the rest of the population.

Symptoms of Limphoma Hodgkin
The main manifestation of lymphoma is lymphadenopathy - increased lymph nodes. This symptom is found at 75 - 80 percent. It increases as peripheral lymph nodes, so intragenic nodes. With this disease, the lymph nodes are dense, with palpation painless and are not laughing among themselves. As a rule, they form different conglomerates in size ( bucket).

To groups of lymph nodes, which are most often increasing with Hodgkin lymphoma include:

• shane-probually;
• axillary;
• inguinal;
• femoral;
• nodes of the mediastinum;
• irregular nodes.

An integral sign of Hodgkin's lymphoma is inxication syndrome. It is characterized by night sweating, a decrease in body weight, long fever within 38 degrees.

With the Lymphoma of Hodgkin, the bone system is very often affected, internal organs. So, the defeat of the bones is found in one third of the patients. At half past cases, this is a spine, in other cases these are pelvic bones, ribs, chest. In this case, the main symptom are pain. The intensity of pain is very pronounced, but also pains can enhance when pressed on affected bones ( for example, when pressing on the spine). Often ( at 30 - 40 percent of cases) The liver is affected, while numerous granulomas are formed in it. Symptoms of liver damage is heartburn, nausea, vomiting, feeling of bitterness in the mouth.

Lymphoma Neakzhkinskaya

Non-Hodgkinsky lymphomas are malignant formations, that is, cancer tumors. Also, this type of lymph is called lymphosarcomes. More than half of all cases of such a tumor are diagnosed in patients over 60 years old. This type of lymphoma is classified according to various features, among which the greatest value is characteristic ( dynamics of development) and localization of the tumor.

Views of Nevatzhkinsky Lymphoma are:

• berkitta lymphoma;
• diffuse large cell lymphoma;
• aplastic lymphoma;
• marginal lymphoma.

Dynamics of lymphosarcoma development
One of the main criteria is the dynamics of the development of the tumor, that is, its character, which can be aggressive or indolent. Aggressive lymphoma is rapidly increasing in size and metastasis ( germinate) To other organs. For indolent formations, the slow development and sluggish current, during which relapses occur ( repeated exacerbations of disease). Interesting is the fact that aggressive lymphomas are best suited to cure, and indolent tumors are prone to unpredictable flow.

Localization of non-Hodgkinsky lymphoma
Depending on the location of the lymphosarcoma, there may be a nodal or extrodal one. In the first case, the tumor is located only in the lymph node, without affecting the neighboring tissues. Such neoplasms are characteristic of the initial stages of the disease. They react positively to therapy, and in most cases the treatment leads to prolonged remission ( symptom sinks).

Extrangal lymphosarcoma is a tumor that struck not only lymph node, but also located near the cloth or organs. In severe cases, such malignant formations affect even bone tissue and / or brain.

Lymphoma Berkitta

Berkitt lymphoma is a variant of lymphoma a very high degree of malignancy. It is characterized by a tendency to spread outside the lymphatic system in blood, bone marrow, internal organs. Burkitt's lymphoma cancer cells take their origin from B-lymphocytes. Unlike other lymphom, this species has its own distribution area, these are the countries of Central Africa, Oceania and the United States of America.

Etiology ( origin) Burkitt lymphoma, like other lymph, is not yet clarified. Radiation, Epstein-Barr virus, adverse environmental conditions plays a major role in origin. There are two forms of Berkitt lymphoma - endemic and sporadic. The endemic form of lymphoma is found in the countries of Central Africa, which is often called African. His difference from sporadic form is the presence of Epstein-Barr virus genome.

The clinical picture depends on the localization of the pathological focus. Initially, cancer cells are localized in lymph nodes, and then they go to the authority they surround. The result of tumor growth is a violation of the function of the organ. If the lymph nodes, increasing, form conglomerates among themselves, then the vessels and nerves are completely squeezed.

The beginning of the disease may be sudden or gradual, which depends on the localization of the tumor. The first symptoms are not nonspecific and might imitate ( remind) Cold. In addition, it is joined by a frequent symptom of lymphoma - fever. Fever is often combined with night sweating and weight loss. These symptoms are a manifestation of general intoxication syndrome. Also, the permanent symptom of Berkitta lymphoma is regional lymphadenopathy ( increased lymph nodes). If the lymphoma is localized at the level of the gastrointestinal tract, the clinical picture of the lymphoma is complemented by the obstruction of the intestine, and in severe cases in intestinal bleeding. When lymphoma localization at the level of the urinary system, the main symptom is renal failure. Its signs are swelling, a decrease in daily diurea ( total urine), violation of the electrolyte balance in the body. As the disease progresses, patients are very thin, they can lose up to 10 kilograms.

Diffuse large cell lymphoma

Diffuse large cell lymphoma refers to lymphomas with a high degree of aggressiveness. Life expectancy at this type of cancer varies within a few months. The primary substrate for cancer cells in this case is in lymphocytes. Most often face of middle and older. At the same time, the primary focus can be located both in lymph nodes and extroductally, that is, outside the lymphatic node. In the second case, the tumor is most often localized at the level of the gastrointestinal tract and the urogenital system.

A separate variant of the large-cell lymphoma is the primary in-large-milking mediastinal lymphoma. It is assumed that it is originally this tumor develops from the fork gland ( timus), which subsequently grows into the mediastinum. Despite the fact that this type of lymphoma is able to intensively grow into neighboring organs, it almost never metastasizes. Suffer a large cell lymphoma most often young women.

For diffuse large cell lymphoma, several variations of development are characterized. In the first case, there is a simultaneous increase in several lymph nodes ( development of lymphadenopathy). This symptom will be the main in the clinical picture of the tumor. A variant is also possible when the tumor is located outside the node in some organ. In this case, the specific symptoms of organ lesion will prevail. For example, during localization in the nervous system, it will be neurological symptoms, during localization in the stomach - gastric symptoms. An option is also possible when the inxication syndrome is in the first place with manifestations in the form of fever, sweating, a sharp decline in body weight.

Lymph Classification according to the degree of aggressiveness

The National Cancer Institute in the United States of America proposed a classification of lymphom based on the average life expectancy of patients. According to this classification, lymphoma is divided into indolent, aggressive and highly aggressive.

Views of lymphoma according to the degree of aggressiveness are:

• Indolecent ( sluggish) - The average life expectancy varies within a few years. These include lymphocytic and follicular lymphoma.
• Aggressive - The average life expectancy is calculated by weeks. These include diffuse laminating lymphoma, diffuse mixed lymphoma.
• High-aggressive - The average duration is calculated by weeks. These include Berkitt lymphoma, T-cell leukemia.

Lymphoblastic lymphoma ( T and B.)

Lymphoblastic lymphomas can develop both T-lymphocytes and lymphocytes V. Morphologically and clinically lymphoblastic lymphoma is very similar to lymphoid leukemia. This type of lymphoma is inclined to the formation of massive tumors, which are often localized in the mediastinum. For lymphoma, the defeat of the central nervous system is characterized with the development of single and multiple nerve lesions. In addition, the transformation of the bone marrow in the type of acute leukemia is noted, which means the formation of blast in the bone marrow ( cancer) cells.

Like all other non-Hodgkinsky lymphoma, lymphoblastic lymphoma is distinguished by a malignant flow. T-cell lymphomas account for about 80 percent, the share of B-cell lymphomas - 20 percent. In progression of the disease, the lesion of the liver, kidneys, spleen is joined.

Marginal and anaplastic lymphoma

Marginal and anaplastic lymphoma are variants of non-Hodgkinsky lymphoma, distinguished by a high degree of malignancy. Marginal lymphoma is a variant of lymphoma that develops from the border ( marginal) Cell zones in the spleen. The marginal zone is the border between the white and red pulp, which contains a large number of lymphocytes and macrophages. This type of lymphoma refers to sluggish tumors.

Anaplastic lymphoma originates from T-cells. With this form, the cell cancer fully loses its characteristics, acquiring the type of "young" cells. This term is called aplasia, where the name of the disease follows.

Lymphoma in children

Unfortunately, the variety of lymphoma aggressiveness is found in children. This category of persons in the share of Lymph accounts for about 10 percent of all malignant formations. Most often diagnosed in children from 5 to 10 years, it is extremely rare in children up to one year.

Children lymphoma are distinguished by increased aggressiveness, rapid metastasis and germination to other organs. That is why children, as a rule, fall into the hospital, already in the later stages ( the tumor is growing rapidly and expands).
The clinical picture of the lymphoma is characterized by the damage to the bone marrow, the central nervous system and the internal organs.

As a rule, there are non-Hodgkinsky lymphoma, while Hodgkin's lymphoma is relatively rare. In the first case, internal organs are often affected, and the intestines and the abdominal cavity. The symptoms of the lymphoma of the abdominal cavity are pain in the abdomen, disruption of intestinal passability ( manifests in the form of constipation) and palpable tumor during inspection. Treatment lies in polychimotherapy. Hodgkin's lymphoma is manifested by painless lymph nodes most often with cervical. Lymphadenopathy ( increased lymph nodes) Combined with increased sweating, fever, body weight loss.

It is important to remember that in children, in view of their age and limited vocabulary, the collection of anamnesis is sometimes difficult. They rarely say that they are bothering them, they cannot specify accurate localization of pain. Therefore, it is important to pay attention to indirect signs of the disease - increased fatigue, weakness, sweating, irritability. Young children often capricious, sleep well, become sluggish and apathetic.

Stages of lymphoma

Stages of lymphoma are the stages of development of tumor-shaped formations. Each stage has a number of specific characteristics, namely the age of the neoplasm, the level of propagation of the tumor process and the degree of defeat of the body. That is why the definition of the stage is very important to choose the most effective tactics of treatment. In medical practice distinguish 4 lymphoma stages.

First stage of lymphoma

The first, the initial stage is characterized by the defeat of one lymphatic node or several lymph nodes, which are in the same zone ( for example, cervical lymph nodes). Lymphoma, localized in the same organ, without concomitant lesion of lymphatic nodes, is also considered as a tumor of the first stage. All the lymphomas of the first stage are local tumors, that is, they do not have metastases into other organs, fabrics.

In addition to the designation of the stage, the tumor is assigned an alphabet designation, depending on which zone of the body it is located. So, if the tumor is in lymph node, the fork gland, spleen or within the lymphoid pharyngeal rings ( cluster of lymphatic tissue in the throat), lymphoma is marked simply by the number I, which indicates the stage. The lymphoma of the first stage, located, for example, in the stomach, intestines and any other organs, is indicated by the additional letter E.

Second stage of lymphoma

The second stage of lymphoma is determined when the tumor affects 2 or more lymph nodes that are on one side of the diaphragm ( muscles located between the chest and abdominal cavity). This type of lymphoma is indicated only by the number II.

A tumor that struck one lymphatic node and located near the tissue or organ, also ranked 2 stages. Tumor processes of this type, except for numbers, are denoted by the letter E.

Third stage of lymphoma

The lymphoma of the third stage is the involvement in the pathological process 2 or more lymph nodes located at a different side of the diaphragm. This type of tumor is indicated only by numbers. The similar stage "is awarded" in situations when lymph nodes from different zones of the body and one body or a piece of fabric are involved in the tumor process, located next to the lymph node. In this case, the tumor is indicated by the letter E.

Also, the 3 stages include lymphomas, which have hit the spleen and several lymph nodes, located on opposite sides with respect to the diaphragm at the same time. Such neoplasms are noted by the letter S. Letters E, S notes the process in which several lymph nodes are involved, adjacent organs and spleen.

Fourth stage of lymphoma

Limphoma last stage relates to disseminated ( massively common) Tumors. The final stage is told in the event that the tumor process does not affect one, but several organs, and at the same time they are separated from the primary localization of the lymphoma.

How many live during lymphoma?

The survival in the lymphoma depends on the stage of the disease, the correctness of the treatment, the age of the patient and the state of its immune system. Achieving continuous ( at least 5 years) remission ( symptom sinksIt is possible in cases where the tumor is diagnosed in the first or second stage, and the risk factors are completely absent.

The following risk factors are distinguished during lymphoma 1 and 2 stages:

• lymphoma is located in the chest, and its dimensions reach 10 centimeters;
• the tumor process, except for lymph nodes, has also spread to any organ;
• cancer cells are detected in 3 or more lymph nodes;
• when surrendering analyzes, the erythrocyte sedimentation rate is noted;
• for a long time, general symptoms are preserved ( night sweats, subfebrile, weight loss).

In general, according to statistics, the successful results of treatment reaches an average of 70 percent ( when a tumor is detected in 2 stages) up to 90 percent ( when a disease is detected at stage 1) Patients.

Survival at the later stages of the disease varies from 30 percent ( for 4 stages) up to 65 percent ( for 3 stages). At this stage, the risk factors are the age of 45 years old, the male floor, when surrendering analyzes, a high level of leukocytes, a low level of albumin, hemoglobin, lymphocytes.

Before use, you must consult with a specialist.

Oncological diseases, namely, cancer formation of lymphocytic type are divided into 2 groups: (lymphogranulomatosis) and. Follicular type lymphoma is a third of other species oncologies of lymphocytic type. Changes in cells forming the main immunity (B-lymphocytes) may cause the development of cancer. This includes follicular lymphoma degree. FL - tumor diagnosed at the initial stage of development is considered a lightweight, safe, treatable and favorable forecast.

Classification and flow stage

Depending on the cytological type, 3 stages of follicular lymphoma are isolated:

1. I type. For this type of FL, the content of centroblasts is not more than 5 in the field of view (expressed by the percentage content, since the calculation is carried out per 100 cells). The cell composition is represented by small cells. Tyment form I cytological type is well amenable to therapy and has a favorable treatment result.
2. II type. With cytological II type, tumor cell populations are contained up to 50%. In the smear, under an increase in the microscope 400 times, there are from 6 to 10 blast cells with signs of centroblast cytomomorphology and centrocytes. The composition of the cells has a mixed form - there are both small and large cells (diffuse growth of growth). With the help of the "shock" dose of chemotherapy, tumor II cytological type is treated. Unfortunately, frequent relapses arise, which causes the need to conduct repeated chemiele groups.
3. III type. Centroblasts appeal from 16 and higher. The cell composition is represented by large cells. This cytological type of lymphoma has an unfavorable forecast. Survival is striving for zero.

In clinical and diagnostic measures for differentiation of the typical affiliation of the follicular lymphoma, a characteristic cytological basis is the presence of follicle-like tumor structures - these are dendritic follicle cells.

Types of follicular lymphoma:

1. Diffuse. Follicular cells that form a tumor are contained in a volume of 25%.
2. Follicular diffuse. The volume, newly formed cells is 25-75%.
3. Fully follicular - The volume of formed tumor cells is more than 75% (B-largecot formations are dominated).

The main causes of the development of pathology

As such, there is no reason for the development of follicular lymphoma, but there are possible provoking factors for the development of oncology:

• autoimmune diseases;
• congenital anomalies associated with genetic coding;
• chromosomal anomalies;
• unhealthy and asocial lifestyle (smoking, alcoholism, toxicization, drug addiction);
• prolonged exposure to carcinogenic and chemical compounds on the body;
• long-term use of immunosuppressants;
• sustain replacement operations for implant and any other operational interventions associated with transplantology;
• viral infections, including human immunodeficiency virus;
• diseases of the blood coagulation system, the red lupus and trophic ulcers are one of them (ICD 10).

All of the above reasons lead to a decrease in immunity, disrupting the formation of in lymphocytes and their main function. Despite the favorable prognosis in the treatment of FL, due to the reduction of the body's resistance, the disease is characterized by frequent relapses.

Limphoma symptoms

Follicular lymphoma according to statistics, meets in men and women older than 55 years. In young age and independently of the floor, follicular cancer does not occur. How many live with a given diagnosis, it is difficult to say - it all depends on the immunity of the disease.

Additional information about the development of cancer of lymph nodes, read in the review

Clinical manifestations are directly dependent on the stage of the tumor. The first two degrees are not accompanied by bright, characterized symptoms of follicular lymphoma. Weakness may appear or minor ailments. At 3 stages, clinical manifestations acquire a bright color, accompanied by:

• elevated temperature;
• rapid fatigue, from minor loads;
• increasing the spleen;
• amplification of sweating in a state of calm and during the night sleep;
• an increase in the inguinal, axillary and cervical lymph nodes (due to the inflammation of the cervical lymph nodes, the affected almonds prevent the correct swallowing process);
• increases belly and full leukemia appears.

As in any other oncology, 3 and 4, the stage of cancer is accompanied by a total damage of the hematopoietic system, the bone marrow and spleen suffer. The defeat of the central nervous system of a person leads to a fatal outcome or severe disablement.

Diagnostic methods

Follicular lymphoma has a hidden course of the disease, and therefore may be in a latent state without manifesting clinically about 10 years. Therefore, it is so important to regularly pass inspections in the oncological dispensary to persons over 57 years. And when the increased lymph nodes are detected, immediately seek help from the therapist or oncologist.

The diagnostic methods are prescribed to refute or confirm the lymphoma. In addition to the patient's survey, learning the history of the patient and palpation of inflamed lymph nodes, the following types of diagnostics are applicable:

1. Blood test for general and biochemical type of research.
2. X-ray of lymph nodes.
3. Ultrasonic diagnosis of the abdominal cavity and its space.
4. MRI and CT.
5. Studying a biopsyth microscope obtained by surgical pathway, or by excised painful lymph node.
6. Immunochemical laboratory reactions. With the help of the techniques used, the cell affiliation of lymphoma is completely accurate.

Therapy

When diagnosing 1 or 2 degrees, the degree of FL is carried out gentle therapy, without the use of radical measures. Only in the event that the process aggressive and rapid chemotherapy is appointed. Fatal outcome at 1 and 2 degrees are not observed. In other, later stages, oncologists are used laser and polyhemical therapy, drugs to raise the immune balance of the body. Detection of oncology in the fourth stage is not subject to treatment.

In the event of a metastase in the bone marrow, the sole proper tactics serves the transplantation of bone marrow tissue. Experimental treatment is the transplant of its own stem cells to the patient. The complexity is that not every person turns into a bank to preserve its stem cells.

Summing up, it can be noted that the methods of treatment of follicular lymphoma do not differ from the treatment of other species of cancer.

Forecast

Prediction in the treatment of cancers depends primarily on the stage of detecting the tumor process. Reviews of doctors say that in cancer processes in follicles of lymph nodes 9 of 10 patients are fully cured if:

• After diagnostic measures, the 1st FL stage is installed.
• 2. The type of disease is confirmed with an inhibitory rate of the progression of the neoplasm.

3 The degree of follicular lymphoma has an unfavorable forecast. At this stage, the current therapy does not benefit. Due to weakened immunity, a secondary infection is joined (for example, pneumonia), which leads in 90% of cases to death. Some factors increasing the risk of developing alert, and their timely diagnosis may contribute to the prevention of the severe effects of lymphoma:

• Anemia, hemoglobin less than 120 g / l;
• Increased norm of LDH in blood biochemistry (lactate dehydrogenase);
• Age for over 60 years;
• Defeat by cancer cells of more than 4 groups of lymphatic nodes.

The degree of malignancy of the follicular lymphoma is determined by the counting of the number of blasts in 10 fields of view with a large increase in the microscope (X40 lens).

GRADE 1. 0-5 centroblasts in sight.

6-15 centroblasts in sight.

Grade 3. More than 15 centroblasts in sight:

3a. There are centricots;

3b. No centrocytes, there are fields of centroblasts.

GRADE 3 follicular lymphoma is considered as an aggressive lymphoma and is treated according to the protocol of diffuse B-large-cell lymphoma.

330.1. International prognostic index for follicular lymphoma (FLIPI-1) (Table 156).

Table 156.

Each parameter is estimated at 1 point: low risk - 0-1 score, intermediate risk - 2 points, high risk - 3-5 points.

330.2. Stage I-II (Grade I and Grade II).

For a small number of patients with limited I-II stages of disease, the radiation therapy should be conducted by extended fields. Erony mode: one-time dose 1.8 grams 5 times a week, total dose - 30-40 grams.

In the presence of a large volume of the tumor (the size of individual lymph nodes is more than 10 cm), treatment is starting with chemotherapy using modes used in common forms of the disease. After 4-6 chemotherapy courses, there are irradiation of areas of lesions and adjacent areas in a total focal dose of 36 gr.

330.3. III-IV Stage (Grade I and Grade II).

For most patients with common III and IV healing therapy, there are currently no stages. Since the natural course of the disease is characterized by spontaneous regression to 25% of cases, chemotherapy should be started only with the appearance of in-symptoms, damage to the bone marrow, the presence of a large volume of tumor, compression of vital organs, the appearance of pleurite / ascites.

In 4 randomized studies, it was shown that the early start of treatment in asymptomatic patients does not lead to an increase in survival.

If the target of therapy is complete remission or long-term illegal survival of the selection therapy serve as rituximab in combination with chemotherapeutic modes: SHOR, SVR, FC or FM. Chemotherapy is carried out until the maximum effect is achieved, and then two additional courses are held.

Monotherapy with monoclonal antibodies (rituximab) or monotherapy with alkylating preparations (chlorambucin) is an alternative for low-risk patients or in the presence of contraindications to conduct more intensive chemisimmunotherapy.

In the presence of contraindications to conducting combination chemotherapy, monochimotherapy chlorambucal can be used.