Non-Hodgkin's lymphomas are a whole group of malignant Hematology Oncology diseases (lymphomas) that cannot be classified as a specific Hodgkin's lymphoma. These are tumors that develop from lymphoid B-cell precursors, T-lymphocytes and NK-cells (natural killers). Lymphomas occur mainly in adults, children are relatively rare. But in children, this type of Hematology Oncology tumors proceeds more aggressively, but responds to specific treatment much more better.
A typical location of lymphoma is a certain lymph node or a group of anatomically close lymph nodes. Such forms of non-Hodgkin's lymphoma are called nodular(or nodal).
Also there are lymphomas that affect not the lymph nodes, but certain internal organs (brain, liver, skin, spleen, kidneys, etc). Such forms of lymphoma are called extranodal. Besides there are mixed forms of damage – with the involvement of both lymph nodes and internal organs in the pathological process.
The main features of Lymphoma’s treatment in children at Medical Center:
- Clinic works in close cooperation with the best Israeli Hematology Oncology centers and according to their reference model.
- All doctors have appropriate qualifications, have completed internships in the best foreign hematology clinics.
- In their work, specialists are guided only by modern global treatment protocols, use highly effective and safe medicines and procedures.
- The approach to each patient is individual. That is, the treatment scheme is not templated for everyone, and drugs, their doses, other diagnostic and treatment procedures are selected for each child separately, taking into account age, state of health, type of tumor, stage of the process, wishes of parents, etc.
- All invasive and painful interventions in children are provided only under general anesthesia, so that children do not feel fear, pain, or any other psychological discomfort.
- Conditions in the wards and departments are very comfortable to stay for a long time. There are all the necessary things for children and their parents or custodians. There are buffets, educational courses, and playrooms at the departments. If necessary, parents and the child can receive psychological help.
- The department employs not only hematologists, but a whole multidisciplinary team: oncologists, pediatricians, radiation therapists, chemo-therapists, infectious disease specialists, immunologists, rehabilitators, surgeons, and other specialists that can create necessary continuous treatment process.
Israeli doctors have achieved incredible success in the treatment and diagnosis of children's Hematology Oncology diseases, including non-Hodgkin's lymphomas. Everything because of successful practical application the latest treatment schemes and modern diagnostic equipment. People come from all over the world to receive a consultation and treatment from the best Israeli specialists in the field of Pediatric Hematology Oncology diseases. One of these specialists is Professor Amos Toren,who heads the Pediatric Hemato-Oncology and BMT department at the Haim Sheba Israel Medical Center. It is a person who manages the Pediatric Hematology project of Maimonides Multidisciplinary Medical Center. All our doctors, regardless of their high qualifications and experience in the Pediatric Oncology Hematology clinic, can at any time receive advice from a professor or order an online consultation for their patient.
Causes and types of non-Hodgkin's lymphoma in children
The direct cause of any malignant tumor appearance, including lymphoma, is a genetic breakdown in one cell, which leads to the uncontrolled growth and division of this cell with the development of a whole defective malignant cells generation. What exactly causes this breakdown is currently unknown.
There are certain risk factors that significantly increase the chances of this disease developing:
- Negative influence of certain factors in external environment – certain chemical substances, for example, benzene, ionizing radiation influence.
- Certain viral infections – HIV, human herpes viruses, human lymphotropic virus, Epstein-Barr virus, hepatitis B and C viruses.
- Primary and secondary immunodeficiency states, autoimmune diseases.
- Previous courses of chemotherapy or radiation therapy.
All non-Hodgkin lymphomas are divided, depending on the progenitor cells from which they originate:
1. Lymphomas from B-lymphocytes. These include, for example, diffuse large B-cell lymphoma, Burkitt's lymphoma, Waldenstrom's macroglobulinemia, anaplastic large-cell lymphoma, lymphoblastic lymphoma, etc.
2. Lymphomas from T-lymphocytes and NK cells. For example, peripheral T-cell lymphoma, large granular lymphocytic (LGL) leukemia, mycosis fungoides, others.
Non-Hodgkin's lymphoma symptoms and stages in children
Unfortunately, there are no such clinical manifestations of lymphoma that would allow an accurate diagnosis, even at an early stage. All non-Hodgkin's lymphoma’s features are non-specific and allow only to suspect the disease. It is possible to confirm it already at the next diagnostic stage.
The most frequent pathological lymphoma’s manifestations include:
- Prolonged fever that cannot be explained by other causes.
- Unmotivated weight loss, lack of appetite.
- Increased night sweats.
- Enlargement of one or more lymph nodes (peripheral or internal). Peripheral lymphadenopathy can be detected independentlya – noticeable lump or it is presence during palpation. As a rule, the internal one is detected accidentally – during ultrasound of the internal organs for other reasons.
- When a certain internal organ is affected, corresponding symptoms will be present - headache, neurological manifestations in case of brain lymphoma, jaundice, liver enlargement – in case of liver damage, etc.
- In the case of secondary bone marrow affection, anemia, thrombocytopenia, etc., may appear.
Depending on the spread of the tumor process in the body, there are 4 stages of non-Hodgkin's lymphoma:
- One lymph node or one anatomical group of lymph nodes is affected by the pathological process. Or there is one extranodal lesion (internal organ) without involvement of adjacent lymph nodes.
- More than 2 groups of lymph nodes on one side of the diaphragm are affected. Or there is one nodal + one extranodal lesion on one side of the diaphragm.
- Lymph nodes on both sides of the diaphragm are affected. Or damage to the lymph nodes above the diaphragm + spleen affection.
- There is 1 or more lesions of lymph nodes on one side of the diaphragm + 1 or more extranodal focus.
1 and 2 disease stages are localized, 3 and 4 – widespread and progressive.
Importantly! The treatment scheme depends on the stage of the disease, so the diagnosis must be provided especially attentively, not to miss even the smallest lymph node in the body that may suffer from the tumor process. Modern diagnostic methods and innovative equipment, which are available to each of our patients, will help to cope with this difficult situation.
Modern diagnosis methods of non-Hodgkin's lymphomas
The success of lymphoma treatment and the prognosis directly depend on the correct and timely diagnosis. Therefore, at Maimonides Medical Center, we pay special attention to the diagnostic stage and are very meticulous about obtained results.
All our patients have access to modern and safe diagnostic methods, innovative genetic tests and the best equipment for medical imaging. If any diagnostic equipment is not available, the patient, together with his parents or custodians, is referred to affiliated medical centers or Israeli partner clinics of Maimonides.
The diagnostic program for non-Hodgkin's lymphomas is like:
- Examination, anamnesis modeling and generalization of all important information from the patient.
- Blood tests general, biochemical, certain infectious markers detection, etc. As a rule, with lymphomas, there are no changes in the general blood test. It is very rare to detect certain deviations from this analysis.
- Biopsy of the affected lymph node. This is an extremely important testing that allows us to verify the diagnosis. As a rule, the entire affected lymph node is removed for analysis, so the procedure from a simple biopsy turns into a small surgery. In children it is provided under general anesthesia.
All biopsies of Maimonides Medical Center patients are sent for revision to the best pathohistological laboratories in Israel, USA, and Germany. Thanks to such "molecular checks" we are absolutely sure of diagnosis correctness and further treatment scheme. - If tumor cells are detected according to the biopsy data, the next stage of modern diagnostics is provided – immunophenotyping and cytogenetic analysis of the obtained material.
This allows us to verify a certain type of lymphoma with 100% accuracy, identify specific receptors on the surface of tumor cells, and find certain types of mutations in these cells. Firstly, this is necessary to select the most effective treatment regimen (different types of lymphoma respond differently to certain treatment scheme).
Secondly, to create medicines for a specific patient based on the obtained data about his tumor, for example, targeted drugs or CAR-T-cell therapy – is personalized oncology, when medicines are created individually for each patient. - Various imaging methods will be needed at the next stage of diagnosis, when the doctor will determine the stage of lymphoma, namely, to examine the entire body centimeter by centimeter not to miss the smallest nodal or extranodal focus. For this purpose, both standard and modern methods are used – digital radiography, internal organs and soft tissues ultrasound, contrast-enhanced CT, contrast-enhanced MRI, MSCT, PET-CT, PET-MRI, and others.
- If a certain extranodal lesion is suspected, additional examination methods may be needed. For example, in case of stomach lymphoma - NHS (gastroscopy), in case of brain or spinal cord affection - lumbar puncture and cerebrospinal fluid examination, trepan biopsy in case of bone marrow damage, etc.
On the basis of the received data, the Pediatric Hematology Oncologists makes an accurate detailed diagnosis, the stage of the disease, and complications if they are present. Based on this diagnosis, an individual treatment plan is made up. In the treatment procedure for this disease, we will use the experience of the best Israeli centers and world standards of evidence-based medicine.
Non-Hodgkin's lymphoma treatment innovations in children
The main non-Hodgkin's lymphoma treatment method in children is chemotherapy. The choice of treatment regimen depends on how well a particular lymphoma subtype responds to primary therapy. This is called risk-adapted therapy. If the disease does not respond well to primary therapy, these patients undergo more intensive chemotherapy courses.
With lymphoma in children, chemotherapy is cyclical. The patient receives the medicine for several weeks in a row, then there is a break for several weeks, then the course is repeated up to the required number of times. The treatment duration depends on the type of lymphoma, the patient's response to treatment, and his individual characteristics. Standard chemotherapy drugs used to treat patients with non-Hodgkin's lymphomas are vincristine, cyclophosphamide, prednisone, doxorubicin, methotrexate, etoposide, cytarabine.
Targeted therapy is a modern direction of personalized treatment in patients with Hematology Oncology diseases. This method is based on the property of targeted drugs to act selectively (they do not affect healthy cells) and purposefully (they attack only a certain type of malignant cells). This is a modern and highly effective method of treating lymphoma, which requires preliminary molecular genetic analysis of malignant cells (at the diagnostic stage after biopsy), as targeted drugs are developed for a specific gene of a parasitic cell (personalized oncology). Targeted therapy is usually used in combination with chemotherapy, radiation, and hematopoietic stem cell transplantation. Examples of targeted drugs are rituximab, brentuximab, crizotinib.
Immunotherapy is the also a modern treatment method, when various components of the patient's own immune system or drugs developed on the basis of certain substances or cells that participate in immune defense reactions are used to destroy tumor cells.
CAR-T cells are genetically modified white blood cells of the patient, which are "trained" to actively seek out and specifically destroy a certain type of malignant cells. The process of CAR-T cells creating is extremely complex and expensive, but this therapy is very effective, especially in patients refractory to standard treatment regimens.
Radiation therapy is of secondary importance for lymphomas. It is used in the case of a persistent and aggressive variant of the disease or t relapse development of lymphoma.
Also, in case of treatment-resistant lymphoma or relapse of the disease, in a complex treatment together with intensive chemotherapy, immunotherapy, and radiation therapy, the patient may be directed to hematopoietic stem cells transplantation of (bone marrow transplantation).
- If the donor is the patient himself before the course of intensive treatment started, such transplantation is called - autologous. His stem cells are selected at the initial stage. After this a full course of intensive chemotherapy, radiation, biological therapy is followed. Then patient’s stem cells transplant back to restore the damaged bone marrow after receiving effective treatment.
- If the donor is a relative or another person who meets certain parameters, then the transplant is called - allogeneic. Allogeneic bone marrow transplantation have more complications compared to autologous ones. Because rejection and graft-versus-host reaction develop more often.
All patients of Maimonides Medical Center can become participants in clinical trials taking place on the basis of the leading Israeli children's Hematology Oncology clinics absolutely free of charge. Sometimes this is the only chance to save the baby's life and ensure a long future without pain.