Advances in the Treatment of Non-Hodgkin Lymphomas
Prof. Dr. Orhan Sezer
In recent years, very important progress has been made in hematological cancers. These advances include our better understanding of the biological characteristics of blood cancers, advances in diagnosis, and success in treatment. Many new drugs in hematology have demonstrated their efficacy in clinical trials. Many new drug groups have also been licensed in recent years. Among the new drugs are various targeted drugs with very interesting mode of action (English “targeted therapies”).
The most common blood cancer types: The most common cancers in hematology are lymphomas, which are lymph node cancers. We divide these diseases into two large groups as Hodgkin lymphoma and non-Hodgkin lymphomas. Non-Hodgkin’s lymphomas constitute a basket of many diseases with different biology and processes, whose treatments are now completely differentiated and have acquired specific characteristics.
The disease that comes after lymphomas in terms of frequency is multiple myeloma, which is seen in the bone marrow and bones. Other common blood cancer types are diseases of white blood cells called leukemia. We divide them into different groups as acute leukemias (acute myeloid leukemia and acute lymphoblastic leukemia) and chronic leukemias (chronic myeloid leukemia and chronic lymphocytic leukemia). Myelodysplastic diseases are diseases that are mostly seen in elderly people and are noticed by the decrease in the number of cells in the blood. Another group is myeloproliferative diseases, these diseases usually manifest themselves with an increase in the number of cells in the blood. In addition to these, there are diseases that are very serious even if they are not cancer, such as aplastic anemia, a disease caused by the bone marrow not producing blood cells. Blood diseases that affect the immune system are also among the important diseases.
Hodgkin Lymphoma: This disease manifests itself with enlargement of lymph nodes. Some patients develop what we call “B symptoms”: weight loss, sweating at night, and recurrent fever. Computed tomography and bone marrow biopsy are usually required to determine the stage of the disease.
Hodgkin lymphoma is one of the most successful types of cancer to treat today. At each stage, it is treated with the aim of completely eradicating the disease. There are some groups in the world that work to make advances in the treatment of Hodgkin lymphoma and carry out large-scale studies, one of which is the German Hodgkin Lymphoma Study Group (GHSG). The factors we call risk factors are important in the patient-specific treatment of the disease. In patients with early stage and no bad risk factors, a short-term ABVD chemotherapy and radiation therapy is sufficient. However, if the disease is advanced, a much more effective treatment (BEACOPP protocol) may be required to completely eradicate the disease and prevent its recurrence.
If relapsed, high-dose chemotherapy and autologous stem cell transplantation are usually the best treatment option for complete eradication of the disease. One of the new drugs, Brentuximab vedotin, is an important source of hope.
Non-Hodgkin lymphomas
We divide non-Hodgkin lymphomas into 3 large groups: Indoline (slow progressive) lymphomas, aggressive (rapidly progressive) and very aggressive (very rapidly progressive) lymphomas. The course and treatment of these diseases show great differences. Non-Hodgkin lymphomas are also divided into 2 groups in terms of immunological cell type: B-cell and T-cell lymphomas. Generally, T-cell lymphomas have a worse prognosis than B-cell lymphomas. Therefore, more intensive and effective treatment methods are chosen in the modern treatment of T-cell lymphomas. While the chemotherapy protocol named CHOP was given to most of the non-Hodgkin lymphomas in the past, today more effective treatments specific to the disease, varying according to the subgroup of the disease, are applied. It is even possible to treat some types of lymphoma with antibiotic agents without the use of chemotherapy. For example, some types and stages of lymphomas that occur in the stomach or eyes can be completely eliminated with antibiotic treatment. In order to choose the most appropriate treatment to be offered to the patient, the subgroup, stage and prognostic factors of lymphoma should be known exactly.
Most common types of Non-Hodgkin lymphomas
Slowly progressive lymphomas Rapidly progressive lymphomas Very rapidly progressive lymphomas
Follicular lymphoma Diffuse large B-cell lymphoma Burkitt lymphoma
Chronic lymphocytic leukemia Majority of T lymphomas Lymphoblastic B lymphoma
Immunocytoma Mantle cell lymphoma Lymphoblastic T lymphoma
Slowly progressive (indolene) lymphomas: Lymphomas in this group can be classified if the disease is in stage I or II It is treated with radiation therapy and with the goal of eradicating the disease. The disease is more often diagnosed in stage III or IV. In these stages, chemotherapy is administered in certain situations, if it is not necessary, the patient is followed without treatment (in English “wait and see”), because in these cases, starting treatment earlier than necessary does not provide an advantage to the patient. When chemotherapy is required in B-cell indolene lymphomas, the chemotherapy drug Bendamustin, developed in Germany, is in some cases both more effective and less toxic than the CHOP treatment. In B-cell indolene lymphomas, a drug called Rituximab, which targets the CD20 molecule on B-lymphoma cells, increases the effect of chemotherapy and significantly affects response rates and response times. In follicular lymphomas, maintenance therapy with Rituximab significantly prolongs the response time. In fact, this treatment also prolongs the survival of patients who have relapsed.
Rapidly progressive (aggressive) lymphomas: Diffuse large B-cell lymphomas constitute a significant portion of aggressive lymphomas. The treatment is applied to completely eradicate the disease and consists of Rituximab and CHOP chemotherapy. In aggressive T-cell lymphomas, the addition of Etoposide to the CHOP protocol (CHOEP protocol) increases the success rate, as demonstrated by German and Scandinavian studies. Because most aggressive T-cell lymphomas have a poor prognosis, high-dose chemotherapy and autologous stem cell transplantation after 6 cycles of chemotherapy play an important role in the permanent control of the disease.
Mantle cell lymphomas, on the other hand, are an aggressive type of lymphoma in which important progress has been made in recent years. In younger patients, a treatment including Rituximab + CHOP and Rituximab + Cytarabin is prescribed. In young patients, stem cells are collected from the patient after this treatment, high-dose treatment and stem cell transplantation give the best results. In elderly patients, maintenance treatment with Rituximab after chemotherapy prolongs survival.
Very rapidly progressive lymphomas: Another group is very aggressive lymphomas. The most important are Burkitt lymphoma and lymphoblastic lymphomas. These types of lymphoma are mostly seen in younger patients. Burkitt lymphoma is the fastest growing cancer in humans. The goal of treatment in these diseases is to eradicate the disease, but this goal cannot be achieved with simple treatments, but the disease is eliminated with chemotherapies consisting of many drugs and reminiscent of leukemia treatment.
