Leukemia is a malignant disease that occurs when the development of normal melodyloe and lymphoid cells stops at some point and the cells proliferate clonally from that stage onwards. 97% consists of acute leukemias and 3% consists of chronic leukemias. 75% of acute leukemias are caused by acute lymphoblastic leukemia (ALL) and 20% are caused by acute myeloblastic leukemia (AML). Chronic leukemias are divided into Ph+ chronic myeloid leukemia and juvenile myelomonocytic leukemia (JMML).
While ALL is seen with a frequency of 3-4 in 100,000 white children, the frequency of AML is one quarter of that of ALL.
The most common age when leukemia occurs is between 2-5 years of age. Leukemias constitute 25-30% of all childhood cancers.
Etiology
Factors known to cause leukemia include environmental factors, viruses and drugs. When environmental factors are mentioned, ionizing radiation and benzene and its derivatives, which are blamed for the formation of AML, come to mind. The most well-known virus is Ebstein Barr Virus (EBV). This is a virus that can cause mature B-cell leukemia and lymphoma. Medicines are drugs used in cancer treatment. Of these, epipodophyllotoxins and alkylating agents may cause AML in the long term. It is possible to list some cases that indicate genetic effects among the causes of leukemia. For example, if one of the identical twins develops leukemia within the first 5 years of life, the risk of developing leukemia in the other is 20%. The chance of a sibling of a child with leukemia developing leukemia is 4 times higher than that of the general population. The risk of developing leukemia increases in diseases such as Down Syndrome, Fanconi anemia and Bloom Syndrome, which are characterized by genetic chromosome disorders. Diseases such as congenital agammaglobulinemia, Shwachman-Diamond syndrome, Ataxia telengiectasia, Li-Fraumeni syndrome, Neurofibromatis, Diamond Blackfan anemia and Kostmann disease, which are also known to occur genetically, create a predisposition to leukemia.
Epidemiology
The disease most commonly occurs around the age of 4. It is more common in white race than black race, but the prognosis of the disease does not differ between white and black race. It is more common in boys than girls. While ALL is rare in North Africa and the Middle East, lymph Lymphoma cancer is more common. ALL is more common in western countries that have completed industrialization than in other countries. It is less common in India and China than in the west.
Acute Lymphoblastic Leukemia
ALL is a disease that occurs as a result of a single abnormal precursor cell, which has the capacity to renew itself and multiply infinitely, becoming malignant. Precursor cells face the risk of developing spontaneous mutations during their normal development. A single mutation may be sufficient for ALL to occur, or more than one mutagenic event may be required. The most common cytogenetic disorder is interchromosomal translocation. In addition, deletions (deletions) of some parts of chromosomes and DNA mutations can also be detected.
Clinical findings
Fever, malaise, loss of appetite, weakness, bleeding, and resistant infections can be counted among the initial findings of the disease. The beginning can be insidious. Physical examination reveals pallor, bleeding on the skin called petechiae, bruises called ecchymosis, infection, enlargement of the liver and spleen, and enlargement of the lymph nodes. It can mimic many diseases. With acute rheumatic fever due to joint and bone curves, with infectious mononucleosis due to enlargement of the liver, spleen and lymph nodes, with immune thrombocytopenic purpura due to petechiae and ecchymoses, with whooping cough due to high leukocyte count, with aplastic anemia due to a decrease in all blood cells. may interfere. Patients may present with bleeding findings, especially M3 (APL), which is a subgroup of AML. Due to kidney involvement, blood in the urine, hypertension and kidney failure may develop. When there is meningeal involvement, headache, vomiting and edema occur at the bottom of the eye.
Evaluation of the patient
First of all, a detailed history should be taken and a detailed physical examination should be performed. Complete blood count, blood biochemistry, bleeding coagulation tests, hepatitis tests, viral serological tests and tuberculosis skin tests should be performed. Bone marrow aspiration and biopsy are required for diagnosis. The bone marrow material taken should be examined in pathology, and the bone marrow should be sent to flow cytometry, cytogenetics and molecular genetics laboratories for examination. mediast It would be appropriate to take a chest x-ray to determine whether there is renal involvement. To rule out central nervous system involvement, the patient should undergo a lumbar puncture and the cerebrospinal fluid should be examined for cellularity. In case of fever, all cultures should be taken and broad-spectrum antibiotics should be started. The patient should have a dental and eye examination before starting chemotherapy.
Laboratory findings
Anemia, increase or decrease in leukocyte count, decrease in neutrophil and platelet count, leukemia cells are seen in peripheral blood smear. There is an increase in serum uric acid levels, potassium, calcium and phosphorus levels. Serum LDH levels increase, immunoglobulin levels decrease in up to 30% of patients. Serum PT and aPTT levels increase and biochemical tests show abnormalities.
Prognostic factors
Initial admission leukocyte count <50,000/mm3 is a sign of good prognosis. Age >1 year and <10 years is a good prognosis sign. The prognosis is poor in babies under 1 year of age. The cell type from which the disease originates is important in prognosis. Early pre-B indicates a good prognosis, mature T cell indicates a worse prognosis. Mature B cell is also a poor prognostic sign. Thanks to the modern treatment protocols used today, the importance of cell type is gradually decreasing. The DNA index of the cells being >1.16 and the number of chromosomes in the cells being above normal are also good prognosis indicators. Some of the genetic abnormalities seen in leukemia cells are good and some are indicators of bad prognosis: 11q23 anomaly, t(4;11), t(11;19), t(9;22) are abnormalities that show a bad prognosis. t(12;21), and t(8;14) anomalies provide a good prognosis. Early response to chemotherapy (percentage of leukemia cells in the bone marrow examination performed on the 7th and 14th days of treatment) is a prognostic determinant. The amount of leukemia cells left behind in the body during treatment (Minimal residual disease) is a prognosis determinant. (MRH day 29) Initial central nervous system involvement is a poor prognostic sign. Features such as liver and spleen size, lymph node enlargement, platelet count, immunological subgroups, and mixed cell type leukemia no longer have prognostic significance.
Leukemia? foma?
Patients sometimes present with very large liver and spleen, large lymph nodes and masses in the chest cavities. In this case, the number of leukemia cells in the bone marrow is checked to understand whether the patient has lymph node cancer (lymphoma) or leukemia. If leukemia cells are more than 25% of all cells, the condition is called leukemia, otherwise it is called lymphoma.
Central nervous system leukemia
Involvement of the central nervous system (CNS) manifests itself with some symptoms. Increased pressure inside the head causes morning headaches, vomiting, fundus edema and 6th cranial nerve paralysis. As a result of the involvement of brain tissue with leukemia cells, paralysis of the cranial nerves, paralysis of the arms and legs, convulsions, gait disorders and hand balance disorders occur. Hypothalamic syndrome is manifested by overeating, excessive weight gain, and facial and body hair growth. Diabetes insipidus occurs as a result of posterior pituitary gland involvement. Back and leg pain, weakness and numbness occur as a result of spinal cord involvement. Hemorrhage may occur in the central nervous system.
Testicular leukemia
Painless swelling is observed in one or both testicles. Testicular recurrence during treatment is seen in 10-23% of patients. Diagnosis is made by biopsy from both testicles. Biopsy may result in false negativity in 10% of patients. An initial leukocyte count of >20,000/mm3 increases the chance of T-cell leukemia, a mass in the chest cavity, and significant lymph node, liver, and spleen size, testicular leukemia. If there is no suspicion on physical examination, there is no need to perform a biopsy.
Treatment
Leukemia treatment has stages such as remission induction, CNS preventive treatment, consolidation, intensification and maintenance. The aim of treatment is to achieve and maintain clinical and hematological remission. When we say remission, there are fever, bone pain, etc. that can be attributed to the disease. It is understood that there are no symptoms such as, liver, spleen and lymph node enlargement or clinical signs of residual leukemia improve, peripheral blood findings return to normal, leukemia cells are below 5% in an otherwise normal bone marrow, and there is no leukemia in the central nervous system or any other organ. � It dies. For CNS treatment, intrathecal (IT) chemotherapy is administered and continued throughout the treatment period. Treatment is performed with methotrexate or a triple drug consisting of methotrexate-hydrocortisone and cytosine arabinoside. IT methotrexate may cause arachnoiditis, characterized by headache, nausea and vomiting. This condition often heals spontaneously. Radiotherapy is also given to patients who initially have CNS leukemia or who do not respond early to chemotherapy. In modern treatment protocols, leukemia treatment lasts between 2.5-3.5 years. Treatment in girls is shorter than in boys. In case of relapse after treatment ends, the prognosis is better than if relapse occurs during treatment. Treatment for mature B-cell leukemia is shorter than other types.
Bone marrow transplantation
Bone marrow transplantation (BMT) is routinely applied to patients in second remission. Patients who relapse more than 30 months after entering remission are treated again with chemotherapy. KIT is reserved for later recurrences. Some leukemia patients with high-risk cytogenetic anomalies should undergo KIT while they are in the first remission.
Treatment of testicular and CNS relapse
The prognosis is poor in CNS and testicular recurrence that occurs during treatment. Treatment should be attempted with aggressive chemotherapy and radiotherapy.
Survival
While the 5-year survival rate from acute leukemia was around 3% in the 1960s, this rate has increased to 88% today.
Supportive treatment
Anemia and thrombocytopenia caused by the disease itself and the drugs used in treatment are treated by giving erythrocytes and platelets. Broad antibiotics should be used during neutropenic fevers. Trimethoprim-sulfomathaxazole chemoprophylaxis is used against pneumocystis Jiroveci infection. In case of exposure to chickenpox virus, varicella zoster immunoglobulin should be given within 72-96 hours. Tumor lysis syndrome, which occurs with the lysis of leukemia cells at the beginning of treatment, should be taken into consideration and treated appropriately.
Acute Myeloid Leukemia (AML)
AML constitutes 15-20% of childhood leukemias. Unlike ALL, the chance of complete cure in AML is about 40-50%. neonatal loess
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