Hematology Department is the specialized department for diagnosis and treatment of benign and malignant diseases of blood. This department is highly specialized in the treatment of lymphoma, multiple myeloma, acute and chronic leukemias and stem cell transplantation (bone marrow transplantation). The physicians in this department take care of lymph node disorders, blood and bone marrow disorders and diseases of the immune system. There are numerous treatment modalities using modern novel drugs, antibodies, targeted treatments, chemotherapy, radiotherapy, and stem cell transplantation.
In recent years, huge improvements could be achieved both in the exact diagnosis and optimal treatment of hematological disorders. Many of the blood diseases can be cured. Since some blood diseases may be life-threatening, they must be properly diagnosed and treated without any delay.
A high-quality care together with its several departments for immunology, blood bank, radiology, intensive care unit and bone marrow transplantation center.
Frequent hematological diseases are:
- Multiple myeloma,
- Hodgkin lymphoma,
- Acute myeloid leukemia (AML),
- Acute lymphoblastic leukemia (ALL),
- Chronic lymphocytic leukemia (CLL),
- Chronic myeloid leukemia (CML),
- Myelodysplastic syndrome (MDS),
- Myeloproliferative diseases,
- Anemia, functional or numerical abnormalities of leucocytes (white blood cells, WBC), erythrocytes (red blood cells, RBC) and platelets,
- Coagulation disorders,
- Diseases of the immune system.
MALİGNANT DİSEASES OF BLOOD: LYMPHOMA, MYELOMA, LEUKEMİA AND BONE MARROW TRANSPLANTATİON
Hematology is the study of blood, blood-forming organs, and blood diseases. Hematology includes immune system, coagulation disorders and bone marrow transplantation. Blood cells are divided in 3 large groups: Red blood cells are called erythrocytes and contain hemoglobin, which transports oxygen in the body. A reduction of hemoglobin is called anemia and may result in fatigue, loss of productivity, dizziness, and shortness of breath. White blood cells are called leukocytes and form the immune system. Disorders of leukocytes may result in frequent or severe infections. Platelets are small blood cells, which are necessary to prevent bleeding.
During the last few years, impressive progress was made both in the diagnosis and treatment of blood disorders. This progress started with a better understanding of the molecular biology of blood diseases. Most importantly, the exact diagnosis of disease subgroups and consequently the delivery of very specific treatments become possible. Novel drugs (“targeted therapies”) were developed during last years and enabled us to improve treatment results. Today, numerous blood diseases and blood cancers can be treated successfully and many of them can be cured.
MOST FREQUENT MALİGNANT DİSEASES OF BLOOD
The most frequently seen malignant disease of blood is called lymphoma. Lymphoma is a cancer of lymph nodes. It frequently involves spleen or bone marrow but can involve every other organ or structure in the body, too, e.g. liver, stomach, bones, kidneys, or lungs. Lymphomas are divided in two large groups called Hodgkin lymphomas and non-Hodgkin lymphomas.
The next most frequently seen malignant disease of blood is called multiple myeloma, a cancer of the bone marrow. Other blood cancers include diseases of white blood cells, called leukemias. Leukemias are diseases with high numbers of circulating leucocytes in blood and are divided into groups as acute leukemias (acute myeloid leukemia, AML, and acute lymphoblastic leukemia, ALL) and chronic leukemias (chronic myeloid leukemia, CML and chronic lymphocytic leukemia, CLL). Myelodysplastic syndrome is a group of diseases, which frequently occur in elderly patients and are associated with a reduction of the number of blood cells. Another group is myeloproliferative disorders, in these cancers blood cells are produced excessively and result in high numbers of red or white blood cells and/or platelets. In addition to these different types of malignant blood diseases, there are several non-cancer diseases of blood, which are also very important to diagnose and treat immediately and properly. Among them, aplastic anemia is a disease of the bone marrow, in which blood cells cannot be produced. Disorders of the immune system are also an important category and result in frequent and sometimes life-threatening infections.
This disease is usually recognized by an enlargement of the lymph nodes. In some patients, lymphoma leads to weight loss, fever, or sweating. These symptoms are calls “B symptoms”. Lymphoma is usually diagnosed by the microscopical evaluation of a lymph node after extirpation. An extensive surgery is totally unnecessary. Further diagnostic procedures include computer tomography and bone marrow biopsy.
In every stage, the aim of the treatment of Hodgkin lymphoma is cure. The treatment must be given in accordance with the stage, i.e. which areas of the body are involved and in guidance of prognostic factors (called risk factors) to predict the outcome. Although in early-stage patients without risk factors a short chemotherapy and low-dose of radiation can be sufficient, in advanced disease a modern and intensive treatment is frequently necessary to eradicate the disease and to achieve a cure.
If Hodgkin lymphoma relapses, high-dose chemotherapy with autologous stem cell transplantation is usually the best option for cure. A novel antibody drug called Brentuximab vedotin has improved the treatment options in relapsed patients.
Non-Hodgkin lymphomas are a group of about 30 diseases with different biology and behavior. Nowadays, the modern treatment of different forms of Non-Hodgkin lymphomas largely differs from one another. Therefore, the correct diagnosis of the specific subtypes using immunohistochemistry, flow cytometry and molecular techniques is extremely important.
According to their clinical behavior, Non-Hodgkin lymphomas are divided in 3 large groups: Indolent, aggressive and very aggressive Non-Hodgkin lymphomas. Indolent Non-Hodgkin lymphomas may be stable for long periods of time or progress rather slowly. Very aggressive Non-Hodgkin lymphomas progress and involve several organs very rapidly and if untreated, they may cause death within weeks.
Both the clinical course and the treatment of different subtypes of Non-Hodgkin lymphomas show great differences. According to the immunological subtype, we divide them in 2 groups: Lymphomas of B-cell and T-cell origin. In general, T-cell lymphomas have a worse prognosis than the B-cell subtypes. Therefore, modern treatment of T-cell lymphomas includes more intensive and effective treatment modalities.
In the past, a chemotherapy combination called CHOP was used in the treatment of the majority of Non-Hodgkin lymphomas. Nowadays the optimal treatment differs according to the distinct subtype of the Non-Hodgkin lymphomas. In certain subtypes, treatment even without chemotherapy can be curative. Antibiotic treatment without chemotherapy, for example, can be curative in some subtypes and stages of gastric and ocular lymphomas. For the optimal treatment, it is crucial to diagnose the subtype and the stage properly and to choose the treatment according to the prognostic factors of the individual patient.
MOST FREQUENT SUBTYPES OF NON-HODGKİN LYMPHOMAS;
- Indolent lymphomas
- Follicular lymphoma
- Chronic lymphocytic leukemia
- Aggressive lymphomas
- Diffuse large B cell lymphomas
- Majority of T cell lymphomas
- Mantle cell lymphoma
- Very aggressive lymphomas
- Burkitt lymphoma
- Lymphoblastic B cell lymphoma
- Lymphoblastic T cell lymphoma
In stage I or II of indolent lymphomas, the treatment of choice is radiotherapy in curative intent. In 80% of the cases, appropriate diagnostic techniques reveal that the disease is in the more advanced stages III or IV. If chemotherapy is needed, modern drugs are frequently both more effective and less toxic that the old CHOP regimen. In some subtypes, maintenance with antibody treatment prolongs both progression-free and overall survival.
Diffuse large B-cell lymphoma is one of the frequent subtypes of aggressive lymphomas. The treatment includes Rituximab, an antibody against CD20 epitope of B-cells, and CHOP chemotherapy. The aim is cure. In aggressive lymphomas of T-cell type, addition of etoposide, a chemotherapy agent, to CHOP protocol (CHOEP protocol) increases the success rate in younger patients. In most of the T-cell lymphomas, the prognosis is less good than in B-cell lymphomas. Therefore, after achievement of a response with chemotherapy, high-dose treatment with autologous stem cell transplantation is a good option to achieve a long-term disease-control and improve survival.
Mantle cell lymphoma was known as a disease with a rather poor prognosis, but recently great improvements were achieved in the treatment of this lymphoma. In patients younger than 65 years, Rituximab + CHOP and Rituximab + Cytarabine given alternately gave the best results. After this treatment, autologous blood stem cells can be mobilized and harvested. A high-dose treatment with autologous stem cell transplantation was shown to improve long-term disease-control and survival. In elderly patients, maintenance treatment with antibody after the end of chemotherapy was shown to improve overall survival.
VERY AGGRESSİVE LYMPHOMAS
Burkitt lymphoma and lymphoblastic lymphoma are subtypes of this category. These lymphomas are most frequently seen in young patients. Unless they are properly treated, these lymphoma subtypes grow and disseminate very rapidly. The aim of the treatment is cure. This aim can be achieved with a complex and intensive treatment. Chemotherapy protocols used in other subtypes of lymphomas do not result in cure usually; therefore specific protocols were developed to treat Burkitt and lymphoblastic lymphomas.
Multiple myeloma is a disease, which usually involves bone marrow and frequently the bones, also. This disease results in changes of the immune system and makes patients more susceptible for infections, can lead to bone fractures and renal failure. Exciting progress has been made in the treatment of this disease. The work of the “International Myeloma Working Group”, which I am a member of, contributed to this progress and resulted in important improvements of overall survival both in young and elderly patients. Using appropriate combination of drugs effective in this disease, the remission rate and the rate of complete remissions were largely increased.
After induction chemotherapy, blood stem cells can be collected from peripheral blood using specific drugs. In patients with adequate organ function, high-dose chemotherapy and autologous stem cell transplantation can be performed with minimal risk. The combination of novel drugs and autologous stem cell transplantation can achieve remission rates up to 95% and complete remission rates up to 70%.
There are novel drugs, which are effective in relapsed multiple myeloma, also. So called proteasome inhibitors and immunomodulatory drugs are among them. Appropriate combinations of drugs effective against multiple myeloma improve the treatment results in relapsed disease.
Acute leukemias are blood cancers, which develop rapidly, and treatment should be started without unnecessary delay. Acute leukemias are divided into two groups: Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The treatment is intensive and complex, the aim is cure. Excellent supportive care with infection prophylaxis and management is crucial. In some subtypes of acute leukemias, allogeneic stem cell transplantation should be performed to decrease the risk of a relapse.
Chronic leukemias lead to increased numbers of white blood cells. These types of leukemias develop more slowly. Chronic leukemias are divided into two groups: Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML). Important progress could be achieved in the treatment of both types of chronic leukemias with novel drugs and targeted treatments. With modern treatment, complete responses and a good quality of life can be achieved in both types of chronic leukemia.