Non-Hodgkin’s lymphomas are a whole group of malignant Hematology Oncology diseases (lymphomas) that cannot be classified as specific Hodgkin’s lymphoma. These tumors develop from lymphoid precursor cells of B-, T-lymphocytes and NK cells (natural killer cells). Lymphomas occur predominantly in adults; children are relatively rarely affected. But in children, this type of Hematology Oncology malformations occurs more aggressively, but responds better to specific treatment.
Lymphoma typical location is a specific lymph node or a group of anatomically close lymph nodes. These forms of non-Hodgkin lymphoma are called nodal (or nodular). There are also lymphomas that do not affect the lymph nodes, but certain internal organs (brain, liver, skin, spleen, kidneys, etc.). Such forms of lymphoma are called extranodal. There are also mixed forms of damage – with involvement in pathological process of both lymph nodes and internal organs.
Unlike adults, non-Hodgkin’s lymphomas in children are more aggressive; there are almost no slowly progressing variants of the disease. Therefore, quick and high-quality diagnostics is a priority in children with suspected lymphoma.
Israeli doctors have achieved incredible success in treatment and diagnostics of childhood Hematology Oncology diseases, including non-Hodgkin’s lymphomas, thanks to practical application of the latest developments in terms of treatment and modern diagnostic equipment. Patients from all over the world come for consultation and treatment with the best Israeli specialists in the field of pediatric Hematology Oncology. One of the leading medical institutions in the field of Pediatric Hematology Oncology is Tel Aviv Medical Clinic. All our doctors have the appropriate qualifications and have undergone training in the best hematology clinics in the world.
In their work, Pediatric Hematology Oncologists are guided by modern global treatment protocols, use highly effective and safe medicines, and innovative treatment procedures. The approach to each patient is individual. That is, treatment regimen is not standard for everyone, but the drugs, their doses, and other diagnostic and therapeutic procedures are selected for each child separately, taking into account age, health status, tumor type, stage of process, wishes of parents, etc.
The Department of Pediatric Hematology Oncology at TAMС employs not only hematologists, but also a whole multidisciplinary team: oncologists, pediatricians, radiation therapists, chemotherapists, infectious disease specialists, immunologists, rehabilitologists, surgeons and other specialists necessary to create a continuous treatment process.
Causes and types of non-Hodgkin lymphomas in children
The immediate cause of any malignant tumor, including lymphoma, is a genetic breakdown in one cell, which leads to uncontrolled growth and reproduction of this cell with formation of a whole generation of defective malignant cells. What exactly causes this breakdown is still unknown. There are certain risk factors that significantly increase the chances of this disease developing:
- The negative influence of certain environmental factors – chemicals, such as benzene, ionizing radiation effect.
- Some viral infections are HIV, human herpes viruses, human lymphotropic virus, Epstein-Barr virus, hepatitis B and C viruses.
- Primary and secondary immunodeficiency conditions, autoimmune diseases.
- Previous courses of chemotherapy or radiation therapy.
All non-Hodgkin’s lymphomas are divided depending on progenitor cells from which they arise:
- Lymphomas from B-lymphocytes. This includes, for example, diffuse large B-cell lymphoma, Burkitt’s lymphoma, Waldenstrom’s macroglobulinemia, anaplastic large cell lymphoma, lymphoblastic lymphoma, etc.
- Lymphomas from T-lymphocytes and NK-cells. For example, peripheral T-cell lymphoma, leukemia of large granular lymphocytes, mycosis fungoides, others.
Symptoms of non-Hodgkin’s lymphoma in children
Unfortunately, there are no clinical manifestations of lymphoma that would allow an accurate diagnosis, and even at an early stage. All manifestations of non-Hodgkin lymphomas are non-specific and only allow one to suspect the disease; it can be confirmed at the next diagnostic stage. The most common pathological manifestations of lymphoma 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 independently – a noticeable bump on the body or it is found by palpation during a routine visit to pediatrician. Internal ones are usually discovered by accident – during an ultrasound of internal organs for other reasons.
- If a certain internal organ is affected, corresponding symptoms will be present – headaches, neurological manifestations in brain lymphoma, jaundice, enlarged liver – if liver is affected, etc.
- With secondary damage to bone marrow, anemia, thrombocytopenia, etc. may appear.
Modern diagnostic methods
Treatment success and prognosis for lymphoma depend on correct and timely diagnosis. Therefore, at TAMC we pay special attention to diagnostic stage. All our patients have access to modern and safe diagnostic techniques, innovative genetic tests and the best medical imaging equipment.
Diagnostic program for non-Hodgkin lymphomas is as follows:
- Examination, collection of medical history and complaints from the patient by a leading Pediatric Hematology Oncologist.
- Blood tests – general, biochemical, identification of certain infectious markers, etc. With lymphomas, there are usually no changes in the general blood test. It is very rare to detect certain abnormalities from this analysis.
- Biopsy of affected lymph node. This is a very important study that allows us to verify the diagnosis. Typically, the entire affected lymph node is removed for analysis, so a simple biopsy procedure turns into a small surgery, which in children is performed under general anesthesia. All biopsy materials of our patients are sent for revision to the best pahology laboratories in Israel. Thanks to such thorough checks, we are confident in correct diagnosis and selection of the most effective comprehensive treatment program.
- If tumor cells are detected according to biopsy, the next stage of modern diagnostics is carried out – immunophenotyping and cytogenetic analysis of obtained material. This makes it possible to verify with 100% accuracy a certain type of lymphoma, identify specific receptors on tumor cells, and find certain types of mutations in these cells. This is required, firstly, to select the most effective treatment regimen (different types of lymphomas give different responses to certain types of treatment). Secondly, to create a medications for a specific patient based on obtained data about his tumor, for example, targeted drugs or CAR-T cell therapy – this is personalized oncology, when a medicine is created individually for each patient, based on data of his tumor.
- Various imaging methods will be needed at the next stage of diagnostics, when doctor will determine lymphoma stage, namely, examine the entire body so as not to miss the slightest nodal or extranodal focus. For this purpose, both standard and ultra-modern methods are used – digital radiography, ultrasound of internal organs and soft tissues, CT with contrast, MRI with contrast, MSCT, PET-CT, PET-MRI and others.
- If a certain lesion is suspected, additional examination techniques may be required. For example, for gastric lymphoma – FEGDS (gastroscopy), for damage to brain or spinal cord – lumbar puncture and cerebrospinal fluid analysis, trephine biopsy for bone marrow damage, etc. Based on obtained data, Pediatric Hematology Oncologist makes an accurate, detailed diagnosis, stage of the disease, and complications, if any.
Based on this diagnosis, an individual treatment plan is developed, which will include the experience of the best Israeli specialists in treatment of this disease and world standards of medical care.
Prognosis for non-Hodgkin’s lymphoma in children
Depending on tumor process spread in the body, there are 4 stages of non-Hodgkin lymphoma:
- The pathological process affects one lymph node or one anatomical group of lymph nodes. Or there is one extranodal lesion (internal organ) without involvement of nearby lymph nodes.
- More than 2 groups of lymph nodes on one side of diaphragm are affected. Or there is one nodal + one extranodal lesion on one side of diaphragm.
- There is damage to lymph nodes on both sides of diaphragm. Or damage to lymph nodes above diaphragm + damage to spleen.
- There is 1 or more lymph node involvement on one side of diaphragm + 1 or more extranodal lesions.
Stages 1 and 2 of the disease are considered localized, stages 3 and 4 are widespread and progressive.
Important! Treatment regimen depends on disease stage, so diagnostics must be carried out especially carefully so as not to miss the slightest lymph node in the body that may be suffering from a tumor process. And modern diagnostic methods and innovative equipment available to each of our patients will help cope with this difficult situation.
Despite the aggressiveness of such a disease as non-Hodgkin lymphoma in children, modern treatment protocols allow us to achieve a high survival rate of more than 90%. Moreover, this figure is not final – the introduction of modern techniques gives hope for better results with the least number of complications and likelihood of relapses.
Modern treatment of non-Hodgkin’s lymphoma
The main treatment method for non-Hodgkin’s lymphoma 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 treatment, such patients undergo more intensive courses of chemotherapy.
For lymphoma in children, chemotherapy occurs cyclically. Patient receives the medicine for several weeks in a row, then there is a break of several weeks, then the course is repeated up to required number of times. Treatment duration depends on lymphoma type, patient’s response to treatment, and his individual characteristics. Standard chemotherapy drugs used to treat patients with non-Hodgkin’s lymphoma are vincristine, cyclophosphamide, prednisone, doxorubicin, methotrexate, etaposide, cytarabine.
Targeted therapy is a modern direction in personalized treatment of Hematology Oncology diseases. This method is based on the ability of a targeted drug to act selectively (without affecting healthy cells) and purposefully (attack only a certain type of malignant cells). This is a modern and highly effective method of lymphomas treatment, which requires a preliminary molecular genetic analysis of malignant cells (at the diagnostic stage after a biopsy), since targeted drugs are selected for a specific target on malignant cell. Targeted therapy is usually used in combination with chemotherapy, radiation and hematopoietic stem cell transplantation. Examples of targeted drugs are rituximab, brentuximab, crizotinine.
Immunotherapy is the name of a treatment method that uses various components of patient’s own immune system or drugs developed on the basis of certain substances or cells involved in immune defense reactions to destroy tumor cells. An example of innovative immunotherapy for non-Hodgkin’s lymphoma is CAR-T cell therapy.
CAR-T cells are genetically modified white blood cells from the patient that are “trained” to actively search for and specifically destroy a certain type of malignant cell. The process of creating CAR-T cells is extremely complicated and expensive, but this therapy is very effective, especially in patients refractory to standard treatment regimens.
Radiation therapy for lymphomas is of secondary importance. It is used for persistent and aggressive variants of the disease or relapse development of lymphoma. Also, in case of treatment-resistant lymphomas or relapses of the disease, in combination with intensive chemotherapy, immunotherapy, and radiation treatment, patient may be indicated for hematopoietic stem cell transplantation (bone marrow transplantation).
If patient acts as a donor before the start of intensive treatment, such a transplantation is called autologous. Its stem cells are selected at the initial stage of complex treatment. Next, patient receives all the necessary course of intensive chemotherapy, radiation, biological therapy, etc., after which a transplantation is performed to restore the damaged bone marrow after receiving effective treatment.
If donor is a relative or other person who meets certain criteria, then the transplantation is called allogeneic. Allogeneic bone marrow transplantation have more complications compared to autologous ones; rejection and graft-versus-host disease are more common.
All patients of Pediatric Hematology Oncology Department of TAMC can become participants in clinical trials. Sometimes this is the only chance to save the baby’s life and provide him with a long future without pain.
