Leukemias (lymphoproliferative diseases) are malignant diseases of the blood system characterized by production an excessive number of immature or abnormal leukocytes in the bone marrow, which ultimately leads to the suppression of normal blood cells formation and causes symptoms associated with pancytopenia (a decrease in peripheral blood of all cells – erythrocytes, platelets, leukocytes).
This is a fairly common group of malignant lesions, both children and adults are affected. For example, the most common form of lymphoproliferative disease among the adult population is chronic lymphoblastic leukemia. It occurs with a frequency of 20 cases per 100,000 population after the age of 60, men are affected twice as often as women.
Modern Hematology Oncology is at a high level of development, and these diseases are especially successfully treated in Israel. That is why Maimonides Multidisciplinary Medical Center chose Israeli medicine as a model for providing medical services to patients with leukemia. Our adult Hematology Oncology Department closely works with the best Israeli Hematology Oncology centers. All clinical cases are conducted jointly by the hematologist, the head of the department and the responsible oncology hematologist directly from Israel. Although all medical and diagnostic procedures are adapted to the realities of life in Ukraine, they take place under the close supervision of the best practicing doctors in Israel. Also, all our hematologists have undergone internships and appropriate training on the basis of well-known Israeli clinics.
If treatment is very expensive and the patient cannot afford to pay for it, he can use the help of “Keren Or for our Child” the Charitable Foundation, under whose patronage the Maimonides Medical Center operates. Depending on the circumstances the fund can pay all or a part of the treatment’s cost.
All our specialists applicatemodern global protocols and clinical recommendations making up an examination plan and treatment scheme. But at the same time, the approach to each patient is individual, because there are no two identical people and two identical diseases. Planning medical and diagnostic procedures, age, gender, main diagnosis, features of tumor cells, presence of severe concomitant pathologies, and wishes of the patient regarding the treatment process are taken into account. Thanks to this approach, we manage to succeed even in the most difficult cases.
One of the main Israeli medicine advantages, which we have successfully implemented at Maimonides Medical Center, is a multidisciplinary approach to each individual clinical case. That is, not only hematologists work in the department, but also other highly qualified specialists who are involved in the complex treatment of our patients. These include oncologists, chemo therapists, radiation therapists, surgeons, psychologists, rehabilitation specialists, infectious disease specialists, hepatologists, physical therapists, and many others. Our medical center uses only modern and safe medical and diagnostic equipment of expert class. If a certain narrow specialist or rare medical and diagnostic equipment is not available, the patient is referred to subsidiary institutions of Maimonides Medical Center or our Israeli partner clinics, where he is guaranteed to receive the full range of necessary medical services.
Leukemia types and causes
Leukemias are usually divided into:
- Acute or chronicbased on the percentage of blast or leukemia cells in the bone marrow or blood.
- Myeloid or lymphoidbased on the predominant origin of malignant cells (from which blood germ the tumor pool of cells originates).
Among the adult population, the following 4 types of leukemia are most common:
- Acute myeloblastic leukemia (AML): 33%.
- Acute lymphoblastic leukemia (ALL): 11%.
- Chronic myeloid leukemia (CML): 15%.
- Chronic lymphocytic leukemia (CLL): 33%.
Other types of leukemia occur much less often and make up 8% of the total number. Among them are:
- Franklin's disease: immunoglobulin heavy chain disease.
- Langerhans cell histiocytosis (also called histiocytosis X),
- Skin Lymphomatosis - Sézary's disease,
- myeloma disease,
- myelosclerosis,
- acute undifferentiated leukemia,
- acute megakaryoblastic leukemia,
- acute monocytic leukemia,
- acute myelomonocytic leukemia,
- acute erythroid leukemia,
- primary Waldenstrom macroglobulinemia,
- chronic basophilic leukemia,
- chronic myeloid leukemia,
- chronic myelomonocytic leukemia,
- chronic monocytic leukemia,
- chronic neutrophilic leukemia,
- chronic eosinophilic leukemia,
- polycythemia vera (PV),
- essential thrombocythemia.
Unfortunately, the exact cause of lymphoproliferative diseases development is currently unknown, but there are factors that can increase the risk of leukemia developing. The risk of leukemia developing increases with:
- exposure to ionizing radiation in anamnesis (for example, a course of radiation therapy for another malignant neoplasm) or certain chemicals (for instance, benzene, some pesticides, polyaromatic carbonates contained in tobacco smoke) – all these exposures can lead to leukemia.
- Certain anticancer drug treatment, including alkylating agents, topoisomerase II inhibitors, and lenalidomide maintenance therapy after autologous stem cell transplantation.
- Viral infection (for instance, human T-lymphotropic virus types 1 and 2, Epstein-Barr virus) can occasionally cause certain forms of CLL.
- Previous hematological disorders in anamnesis, including myelodysplastic syndromes, as well as myeloproliferative neoplasms, which can lead to the development of AML.
- Existent genetic factor (for example, anemia Fanconi, Bloom syndrome, ataxia telangiectasia, Down syndrome, xeroderma pigmentosum, Li-Fraumeni syndrome) that can lead to acute myeloid leukemia and acute lymphoblastic leukemia.
Leukemia symptoms
For some time, lymphoproliferative disease is asymptomatic. At this stage, the diagnosis is established only by the results of blood tests performed accidentally for another reason. As a rule, the symptoms of leukemia usually appear a few days or weeks before the diagnosis is made, because it is these symptoms that make you seek medical help.
The most common symptoms are associated with a hematopoiesis violation (blood formation in the bone marrow) and with subsequent development:
- anemia (erythrocytes and hemoglobin decrease),
- thrombocytopenia (platelets decrease in level),
- leukopenia (leukocytes decrease in the level).
Anemia can be manifested by fatigue, weakness, paleness, constant malaise, breath shortness during physical exertion, frequent heartbeat and chest pain.
Thrombocytopenia can lead to mucous membranes bleeding, small bruises, punctate hemorrhages/hemorrhagic rash, nosebleeds, bleeding gums and heavy menstrual bleeding. Hematuria and gastrointestinal bleeding develop rarely. Patients may experience spontaneous intracranial or intraabdominal bleeding.
Leukopenia can lead to a high risk of infections developing, including bacterial, fungal, and viral etiologies. Patients may experience fever and severe and/or recurrent infection.
Organs infiltration by leukemic cells leads to enlargement of liver, spleen and lymph nodes. Bone marrow and bone tissue infiltration can cause bone and joint pain. Infiltration of tumor cells into the CNS (central nervous system) and meningeal infiltration are common and can lead to cranial nerve damage, excruciating and persistent headache, visual or auditory symptoms, altered mental status, and transient ischemic attack/stroke.
Leukemia diagnosis methods
As you know, the earlier the diagnosis of a malignant disease is established, the better prognosis and treatment result. Therefore, high-quality and quick diagnosis is an extremely important stage.Maimonides Medical Center applies only modern, expert-class equipment, all our doctors perfectly master all treatment methods of a leukemia suspected patient, are able to correctly interpret the received data, which helps them create a modern, individual and effective treatment plan.
The list of diagnostic procedures at Maimonides Medical Center for suspected leukemia consist of:
- General and biochemical blood tests, various antibodies determination in the blood, assessment of blood coagulation, etc.
- Ultrasound . Providing a puncture biopsy under ultrasound control.
- Bone biopsy and bone marrow aspiration with followed myelogram analysis – a modern method that makes it possible to diagnose a large number of blood diseases.
- Lymph node biopsy with cytological and histological examination of the biopsy spesimens.
- Blood cells and tumor cells immunophenotypingis a highly informative method of verifying the diagnosis, which allows us to establish which blood cells the tumor originates from and which treatment scheme to choose so that the treatment is most effective.
- Modern methods of medical imaging are actively used in hematological diseases and their complications . A doctor receives a lot of useful information with the help of digital radiography, CT, MRI, PET-CT, PET-MRI, MSCT, bone scintigraphy and their various modifications.
- Scintigraphy helps to visualize the primary tumor and its metastases in the patient's body, after which they can be actively affected.
- Lumbar puncture with subsequent examination of cerebrospinal fluid can be used in patients with suspected CNS organs tumor in the case of some hematological diseases.
We send all materials after the biopsy to the world's best pathogistological laboratories (Israel, Germany, USA).Thanks to such double checks, we are absolutely sure of diagnosis correctness and effectiveness of the selected treatment tactics.
Our patients also have access to innovative molecular diagnostics of biopsy specimens (molecular genetic studies). This is an obligatory part of modern oncological diseases diagnosis. As is known, the direct cause of many tumors is a mutation in a certain gene. Thanks to molecular genetic diagnostics, we can find these mutations and choose the most effective treatment regimens, because on the type of changes the response to the effect of certain drugs depends. An example of such modern diagnostics are test systems for molecular genetic testing. Such as Foundation One and Caris Molecular Testing.
All necessary diagnostic procedures can be performed directly in the clinic, without leaving Ukraine.
Leukemia modern treatment
One of the most important advantages of malignant blood diseases treatment at Maimonides Medical Center is the application of a comprehensive approach to each individual clinical case. In fight against the disease, our doctor uses the entire available methods arsenal. Therapy is always a combination of two, three, or even more methods. As a rule, the treatment scheme includes systemic drug chemotherapy in combination with radiation therapy and hematopoietic stem cell transplantation. In some cases, certain innovative treatment methods are added to the treatment program (targeted drugs, immunobiological drugs, etc.).
Chemotherapy is the main way of leukemia treating. To eliminate the maximum number of malignant cells, the first stage of treatment includes high-dose polychemotherapy. Most often, chemotherapy drugs are injected intravenously, but intrathecal (into the spinal canal) method of injection is possible too. Archieved a stable remission, the patient is prescribed supportive chemotherapy courses, during which the patient is prescribed low doses of chemotherapy drugs.
At Maimonides Medical Center we apply only high-quality and safe drugs for chemotherapy from proven well-known companies. For a certain lymphoproliferative diseases treatment, various combinations and regimens of cytostatics are used:
- BEACOPP protocol;
- BEACOPP-esc protocol;
- BEACOPP-14 protocol;
- Stanford IV, Stanford V protocol, COPP schemes, ABVD;
- MOPP protocol;
- COPP protocol. Scheme of ChlVPP.
In each individual case, the scheme and protocol of chemotherapy and immunotherapy is selected by the doctor, based on the diagnosis, type of tumor, patient's condition, presence of accompanying health problems, response to treatment.
Targeted therapy is a type of immunobiological therapy in which targeted drugs act exclusively on malignant cells, so they are very well tolerated by patients. Unlike chemotherapy, targeted drugs have minimal side effects. This is a relatively new direction of Hematology Oncology, which is used both independently and in combination with other methods. Numerous studies have shown that targeted therapy significantly prolongs patient’s life and improves its quality.
Targeted drugs action principle used for hemoblastosis treatment. It consists of у unerring recognition, inhibition of enzymes,receptors synthesis and activity, which take part in new malignant cells formation. As a result, metabolic processes necessary for vital activity are blocked exclusively in cancer cells. Gradually, the number of tumor cells decreases. Targeted therapy does not cause serious side effects, therefore it is also recommended for weakened patients.
Today, a large number of targeted new generation anti cancer drugs are available to applie, for example, therapeutic monoclonal antibodies (rituximab, alemtuzumab, zevalin, milotarg , and others), which are obtained by genetic engineering.
CAR-T therapy is an innovative immunotherapy method that has been relatively recently introduced into the practice of hemoblastosis treating. This technique is based on developing the ability of the patient's T-lymphocytes to quickly recognize the cells of a specific tumor. Modification and "training" of obtained from the patient T-lymphocytes are conducting with the help of genetic engineering laboratory methods. Since CAR-T therapy is associated with the development of side effects, it is not prescribed for debilitated elderly patients. At the same time, its use in children and adults provides stable remission in more than 92% of cases.
Radiation therapy is used in hemoblastosis complex treatment. Remote irradiation of a malignant focus prevents the chaotic division of cancer cells, helps to alleviate the pain syndrome, eliminates certain pathological symptoms, for example, swelling. With neuroleukemia, the brain structures are exposed to ionizing radiation, which significantly improves the patient's condition. In our medical center, radiotherapy sessions are provided on modern devices that allow precise irradiation of the tumor focus, with minimal impact on healthy tissues.
Bone marrow transplantation is also used in leukemia complex treatment. The procedure is providing in two stages. First, the patient is prescribed high-dose chemotherapy, which leads to complete suppression of the hematopoietic system, after which a transplant procedure of one's own (autotransplantation) or donor (allotransplantation) bone marrow is conducted.
There are several types of bone marrow transplantation:
- Autologous - hematopoietic cells transplantation of the patient himself, which were previously taken from him. This procedure is provided for certain diseases that do not have a genetic factor at their core. For example, before a course of chemotherapy, stem cells from the patient's bone marrow are collected, and when the course of chemotherapy is completed, they are injected back into the body. Thanks to this the normal production of blood cells is restored. It is almost never used for leukemia.
- Allogeneic – this type of transplantation consists of hematopoietic stem cells introduction taken from a suitable donor into the patient. This is the best treatment method of the blood system malignant tumors. Especially those caused genetically, like leukemia.
Before the bone marrow transplantation, patient must undergo chemotherapy to destroy all malignant cells. A feature of this treatment is a large dose of drugs that kill not only all malignant cells, but also healthy bone marrow cells. Therefore, during this period (between chemotherapy, direct grafting procedure and the time of new bone marrow engraftment), the body becomes completely defenseless against any infection. That is why it is so important to follow all the rules of anti-infection control , and to minimize different risks. That’s why patient is placed in a sterile box during this period.
After treatment, the patient undergoes arecovery course in the clinic's rehabilitation center rehabilitation center under the supervision of high-level rehabilitation specialists. This significantly improves the prognosis and reduces long-term side effects from therapy. In each individual case, the decision about certain treatment methods combination is made jointly by a team of specialists.
Each person and their disease is different, so in leukemia treatment our doctors, relying on their experience, often go beyond the standard protocols, changing the treatment regimens and doses of necessary drugs, the radiation technique in order to get the best possible results for their patients.