Lymphomas from T- and B-cells (non-Hodgkin's lymphomas, NHL) are a group of malignant diseases characterized by a tumor growth from lymphoid cells, which are normal precursors of B-lymphocytes, less often T-lymphocytes or natural killer (NK). This disease rarely occurs in children, adults are more often affected. Lymphomas are characterized by the presence of a initial tumor formation, which makes them similar to solid tumors, unlike leukemia, when the lesion is immediately widespread.
In the vast majority of cases, lymphoma develops in a single lymph node (nodal forms). But there are also extranodal forms, when not a lymph node is affected, but some internal organ, for example, the liver, spleen, brain, thyroid gland, etc.
NHL are relatively benign tumors by its nature. They have a long course, do not have pronounced symptoms, and sometimes do not require any treatment at all. There are also aggressive forms of lymphoma that, without treatment, can kill a patient in a few weeks. In addition, there are different intermediate options.
One of the leaders in NHL treatment among children is Israel. Children's onco-hematology departments are staffed by doctors who are well-deservedly known all over the world. One of them is Professor Amos Toren (the head of the Pediatric Hemato-Oncology and BMT department at the Haim Sheba Israel Medical Center). He is a leading specialist, who manages the Pediatric Hematology project at our Maimonides Medical Center. All doctors working in Hematology Oncology Department of our clinic have undergone appropriate training and have high qualifications and practice experience with hematology oncology diseases in children.
Today, medicine is developing actively. First of all, this concerns such fields as oncology and hematology. Therefore, compared to the possibilities of lymphoma treating in children 5-10 years ago, we have made significant progress in these processes. Yes, the disease isn’t simple at all, with a serious prognosis! But in most cases it is possible to defeat it completely and restore a good quality of life after a course of treatment. And this became possible because various clinical trials are held, the latest treatment protocols are implemented, modern equipment for accurate diagnosis are provided and new effective drugs are invented.
In its work the Pediatric Hematology Department Maimonides Multidisciplinary Medical Center is guided by the main Israeli approaches to the children’s treatment:
- All therapeutic programs and protocols respond the modern evidence-based medicine standards and are built on the best global treatment protocols. At the same time, doctors use an individual approach to each child and his clinical case. All diagnostic and therapeutic procedures are selected for every child, their safety and effectiveness are constantly monitored.
- Comfortable conditions for children and their parents or custodian to stay. Wards and departments are equipped with everything necessary for the long-term stay of patients, because the process of lymphoma treating is long-term. There are playrooms and classrooms at the departments, children are entertained by animators.
- Doctor’s High qualification and broad practice experience in Pediatric Oncology Hematology Department, only modern and safe equipment applying for diagnosis.
- Treatment and care of small patients is provided not only by hematologists, but a whole multidisciplinary team. If necessary, oncologists, radiation therapists, chemotherapists, rehabilitators, pediatricians, infectious disease specialists, immunologists and other specialists are involved in the diagnostic and treatment process.
Causes and types of non-Hodgkin's lymphoma
The immediate cause of most NHL is unknown. There are several risk factors that increase the likelihood of developing lymphoma in children:
- Adverse effects of environmental factors (some types of chemicals, benzene, herbicides, pesticides, ionizing radiation).
- Some viral infections influence (HTLV-1, EBV, HIV, HHV-8, HCV viruses).
- Certain bacterial infections Impact (H. pylori).
- Autoimmune diseasesprimary and secondary immunodeficiencies.
- Chemotherapy in anamnesis (especially in combination with radiation therapy).
Among the main types of non-Hodgkin lymphoma are:
- B-cell lymphoma (DLBCL)lymphomas from small B cells (chronic lymphocytic leukemia and lymphoma from small lymphocytes, lymphomas from marginal zone cells, follicular lymphoma, lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia, lymphoma from mantle cells), lymphomas from large and medium B cells (B-cell diffuse lymphoma and its types, B-cell lymphomas with a high degree of malignancy, Burkitt's lymphoma).
- Natural killer/T-cell lymphoma (NKTL)peripheral T-cell lymphoma without additional characteristics, leukemia from large granular lymphocytes, mycosis fungoides, and others.
Lymphomas recovery statistics in children
To describe the prognosis, oncologists use the term “5-year survival”, which refers to the number of patients who survived 5 years after diagnosis.
The patient’s overall 5-year survival with this pathology is 72%. These are very good indicators that will only grow with new and effective therapy methods implementation into clinical practice.
Lymphoma symptoms and stages in children
Unfortunately, there are no pathognomonic symptoms for lymphoma, only a detailed testing with a biopsy and histological examination will allow to make the correct diagnosis. But you can suspect the disease if the following signs are present:
- prolonged fever for no apparent reason;
- night sweating;
- unmotivated weight loss;
- lymphadenopathy (lymph nodes enlargement) – a long-term increase of one, a whole group of lymph nodes or several both peripheral and internal;
- in the case of extranodal forms – symptoms of corresponding localization tumor, for example, an increase in liver, jaundice appearance, ascites in liver lymphoma, etc.;
- symptoms of bone marrow damage – increase in the total number of leukocytes in blood or their decrease, anemia, thrombocytopenia.
There are distinguished 4 stages in the clinical course of the disease:
- One lymph node is affected, or one anatomical group of lymph nodes, or an extranodal focus without adjacent lymph node damages.
- More than 2 groups of lymph nodes on one side of the diaphragm.
- Affected lymph nodes on both sides of the diaphragm or lymph nodes above the diaphragm with simultaneous spleen damage.
- Extranodal organ damage with lymph nodes damage.
The selected treatment scheme depends on the stage of the process, so the diagnosis must be executed very carefully and every square centimeter of the patient's body must be examined with modern methods of medical imaging.
Modern diagnosis of non-Hodgkin's lymphomas at Maimonides Medical Center
All patients with suspected lymphoma undergo thorough diagnostic program to confirm the diagnosis, establish the type of tumor, determine the spread of the process and its stage. For this purpose, the following modern diagnostic procedures are used:
- Laboratory studies: general and biochemical blood analysis, blood protein fraction tests, studies for the infection presence of some related ones – HIV, viral B and C hepatitis, Epstein-Barr virus, cytomegalovirus.
- Neoplasm biopsy with followed histological and immunohistochemical biopsy specimens study. It is important that we send all materials after the biopsy for revision to the best Israeli, German, and American pathogistological centers. Thanks to such "molecular checks", we are absolutely sure of the diagnosis correctness and selected therapy scheme adequacy.
- Nodal and extranodal lesions detection using CT with contrast, PET-CT, MRI. If the clinic does not have any necessary equipment for diagnosis, the patient is referred to subsidiary medical centers or Israeli partner clinics of Maimonides.
- Sometimes, we need to provide different other studies studies when lymphomas of certain locations are suspected. For example, bone marrow aspiration and trepan biopsy, various endoscopic examinations (bronchoscopy, cystoscopy, laparoscopy, thoracoscopy, gastroscopy), lumbar puncture and cerebrospinal fluid analysis, etc.
- Molecular genetic tests are used to detect certain types of lymphomas, and when we need to select personalized immunotherapy (biological, targeted).
If any of the procedures are invasive and accompanied by pain, they are provided only under general anesthesia in children. Thus children do not feel pain, fear or other psychological discomfort.
Innovations in lymphoma treatment
Thanks to modern advances in the hematology oncology treatment lymphoma it can be completely defeated, despite the fact that it is a serious malignant disease. Israeli medicine has achieved particularly great success in this field. Doctors at Maimonides Medical Center also took over the invaluable experience from Israeli mentor colleagues. Choosing treatment for each individual patient, we do not use only template protocols, but a personalized approach. Undoubtedly, all treatment schemes are based on modern protocols and global recommendations, but also we take into account the individual patient’s characteristics, his state of health, wishes for the future and other important factors.
Radiation therapy is widely used in the all malignant diseases treatment, including lymphoma. It can be remote (when the radiation source is outside) or contact (when radioactive isotopes are placed directly into the tumor tissue). In the first case, modern and safe devices are used – linear accelerators, in the second - brachytherapy. Irradiation leads to damage of tumor cells reproduction processes and their normal functioning, which leads to the immediate death of the tumor. Unfortunately, radiation also affects healthy body cells, causing a number of side effects. Importantly! The more modern radiation therapy machine is, the safer it is. In our practice, we use only innovative expert-class equipment, so all risks of side effects are minimized. Radiation therapy can be provided as one of the main methods of lymphoma treating, or in combination with other methods, for example, before a bone marrow transplantation procedure.
Chemotherapy is also actively used to treat patients with leukemia. The basis of the method is various chemotherapy drugs introduction of into the body, which lead to the death of malignant cells. Chemotherapy is a systemic treatment, it affects the whole body, which is why most of the side effects of this treatment method are related. In our practice, we use only proven drugs from well-known manufacturers around the world, so we are sure of their effectiveness and reliability. The choice of a specific drug for chemotherapy depends on the main diagnosis, the type of lymphoma, the stage of the process, the patient's condition, the type of Hematology-oncology course (relatively stable or aggressive).
One of the most modern treatment options for lymphoma is targeted therapyDrugs with targeted action block the growth factors receptors on the surface of a malignant cell (class of monoclonal antibodies) or disrupt the synthesis of proteins that transmit signals to cell division (class of low molecular weight inhibitors). In this way, the cell stops functioning normally, reproduces and eventually dies on its own. A great advantage of targeted drugs is their effect only on tumor cells. This is a modern and highly effective treatment method requires preliminary molecular genetic analysis of tumor cells. Because targeted drugs are developed for a specific gene of a malignant cell (personalized oncology). Targeted therapy is usually used in combination with radiation, chemotherapy, and a bone marrow transplantation.
Immunotherapy for lymphomas is a modern treatment method based on immune system activation and its "training" to fight against malignant cells. On leading Israeli Medical Centers researches of various immunotherapy types application are ongoing. Every day, new immunotherapy medicines are introduced into clinical practice – monoclonal antibodies, checkpoint inhibitors of the immune response, CAR-T cells therapy, etc.
CAR-T cells therapy is one of immune (biological) therapy types with Hematology-oncology diseases. This is an innovative treatment method in which the patient's leukocytes are genetically programmed to destroy certain types of malignant cells. During the procedure, a blood sample is taken from the patient. After this leukocytes are extracted from it using modern equipment in genetic engineering laboratory. Next, these cells are modified so that chimeric antigen receptors(CAR) appear on their surface. Then they are cloned to increase their number and returned to the patient's bloodstream. Now the chimeric antigen receptors on the surface of the modified T-lymphocytes will actively search for the corresponding malignant cells in the body, connect with them and destroy.
One of the main methods of treatment for patients with non-Hodgkin's lymphoma is bone marrow transplantation. To date, more than 1 million stem cell (bone marrow) transplants have been performed and this number is growing every day, giving patients with serious blood disorders a chance for a long and healthy future.
There are 2 main types of bone marrow transplantation, depending on the source of the donor material – autologous and allogeneic.
- Autologous transplantation. The donor is the patient himself. At this case, the selection of stem cells is provided before any treatment. And after a course of chemotherapy, radiation therapy, targeted drugs, and immunotherapy, healthy bone marrow cells are returned to the patient and they successfully populate the bone marrow and normal blood formation is restored. This method is safer, as rejection reactions do not develop, because the material is 100% native to the recipient. Unfortunately, this treatment is suitable only in cases where the tumor process does not initially spread to the patient's bone marrow. In the case of bone marrow primary damage diseases, own cells are not suitable for transplantation, and a donor must be sought.
- Allogeneic transplantation is the cells transplantation from a donor (relative or unrelated). This method is best suited for bone marrow primary damage disease treatment, for example, leukemia
The procedure of bone marrow transplantation is complected, requires the high-tech equipment application, qualified specialists, with experience in this field, so you need to trust only proven doctors and medical centers. One such clinics is Maimonides Multidisciplinary Medical Center and its Israeli partner medical institutions.