What Is Acute Medicine?

Acute leukemia (AL) is a malignant clonal disease of hematopoietic stem cells. At the time of onset, abnormal primitive cells and immature cells (leukemia cells) in the bone marrow proliferate, accumulate in the bone marrow and inhibit normal hematopoietic, and extensively infiltrate the liver, spleen, and lymph nodes Wait for extramedullary organs. Presented with signs of anemia, bleeding, infection and infiltration. According to the types of cells involved, AL can generally be divided into two categories: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The incidence of AML in China is about 1.62 / 100,000, while ALL is about 0.69 / 100,000. More common in adults with AML and more common in children with ALL. If acute leukemia is not treated, the average survival time is only about 3 months, and the short-term patient will die even a few days after diagnosis. After modern treatment, many patients have achieved remission and long-term survival, or even cured.

Basic Information

English name: acute leukemia
Visiting department: Hematology

Common causes: May be caused by ionizing radiation, chemical, viral, genetic, etc.
Common symptoms: Pale, tired, bleeding, fever, pain in bones and joints

Causes of acute leukemia

The cause of leukemia has not yet been fully elucidated. The more recognized factors are:

Ionizing radiation

Ionizing radiation such as gamma rays and X-rays can cause leukemia. Among the survivors who received X-ray diagnosis and the atomic bomb explosion, the incidence of leukemia was significantly higher than that of the normal population. The incidence is also related to radiation dose, time and age.

2. Chemical factors

Benzene, antineoplastic agents such as alkylating agents can cause leukemia, and the drug bismorpholine, which is used to treat psoriasis, has been linked to the onset of acute promyelocytic leukemia (APL). Hair dye and smoking may also be related to the onset of leukemia , Especially acute nonlymphocytic leukemia (ANLL).

3. virus

For example, a type C retrovirus, human T lymphocyte virus- (HTLV-1), can cause adult T-cell leukemia; studies have confirmed that the virus can be transmitted vertically from mother to child, or through blood product infusion and sexual contact. And horizontal spread.

4. Genetic factors

Familial leukemia accounts for 7 of leukemia. Identical twins are three times more likely to develop leukemia than other people. Congenital diseases such as Fanconi (Fanconi syndrome) anemia, Downs syndrome, Bloom syndrome and The incidence of leukemia such as congenital immunoglobulin deficiency is higher.

5. Other blood diseases

Such as chronic myeloid leukemia, myelodysplastic syndrome, myeloproliferative diseases such as primary thrombocytosis, myelofibrosis and erythrocytosis, paroxysmal hemoglobinuria, multiple myeloma, lymphoma and other blood diseases. Can develop into acute leukemia, especially ANLL.

Clinical manifestations of acute leukemia

The onset was mixed. Onset is insidious and gradually progresses within weeks to months, or the onset is rapid. Clinical signs and symptoms are caused by bone marrow failure or leukemia cell infiltration.

Anemia

Anemia is often the first symptom of leukemia, with half of the patients having severe anemia at the time of consultation. Pale, tired, sleepy and weak are common, and they develop progressively and are related to the severity of anemia.

2. bleeding

More than half of the patients show early bleeding with varying degrees of severity, and the site can be spread throughout the body, showing bruises, ecchymosis, nosebleeds, bleeding gums and menstrual bleeding, fundus bleeding, etc. The major bleeding is platelet reduction and platelet function. Abnormalities, reduced coagulation factors, and infiltration of leukemia cells, bacterial toxins, etc., damage blood vessels and cause bleeding. Acute promyelocytic leukemia is often accompanied by diffuse intravascular coagulation (DIC) and extensive systemic bleeding.

3. Fever

Fever can also be an early manifestation of patients with leukemia, mainly related to infection caused by agranulocytosis and fever of leukemia itself. Most patients have varying degrees of fever at first diagnosis. Leukemia itself can have low fever and night sweats, and body temperature recovers after chemotherapy. Higher fever often indicates secondary infection, which is mainly related to a significant decrease in mature granulocytes. Common infections are gingivitis, stomatitis, angina, upper respiratory tract infection, pneumonia, enteritis, perianal inflammation, etc. Severe infections include sepsis.

4. infiltration

(1) Lymph nodes and hepatosplenomegaly are more common than acute and non-lymphatic, and the degree of swelling is also more significant. Mediastinal lymphadenopathy is mostly seen in T-cell acute lymphoblasts.

(2) Bone and joint pain often have tenderness at the lower end of the sternum. Leukemia cells infiltrate joints, periosteum, or excessive proliferation in the medullary cavity can cause bone and joint pain, which are more common in children. Acute lymphocytic is more common and significant than acute non-lymphocytic. Bone pain can occur when bone marrow is necrotic.

(3) Acute single and acute myelomonocytic leukemia are common in skin and mucosal lesions . Leukemia cell infiltration can be manifested as gingival hyperplasia or swelling, and specific skin damage is manifested as diffuse maculopapular rash, purple-blue skin nodules, or masses. Acute non-gonorrhea-associated benign skin lesions include Sweet syndrome and gangrenous purulent skin disease, and hormone therapy is effective.

(4) Central nervous system leukemia With the increase in leukemia remission rate and prolonged survival, central nervous system leukemia (CNSL) has become a more prominent problem. Acute gonorrhea is more common than acute non-gonotropic, and acute promyelocytic leukemia is also more common. Often asymptomatic, it can manifest as headache, dizziness, irritability, severe vomiting, neck stiffness, optic nerve papillary edema, and cerebral nerve, spinal cord paralysis and even death.

(5) Green tumors are also called granulocytic sarcomas or medulloblastomas. They are found in 2% to 14% of acute non-lymphocytic tumors. They are called green because a large amount of myeloperoxidase in leukemia cells turns green under dilute acid conditions Tumors often involve bone, periosteum, soft tissue, lymph nodes, or skin, but the most common are the orbital and paranasal sinuses. Can manifest as eyeballs, diplopia or blindness.

(6) Testicular leukemia cells infiltrate the testis, and it is the second cause of extramedullary recurrence of leukemia after CNSL in male children or young people. Mainly manifested as painless swelling on one side, more acute than non-acute.

(7) Other leukemia cells can also infiltrate the heart, respiratory tract, and digestive tract, but clinical manifestations are few. About 10% of ALL (mostly T-ALL) patients may develop anterior mediastinal (thymus) infiltration, which may cause superior vena cava syndrome or superior mediastinal syndrome. Pleural effusion is more common in acute showers. Renal infiltration is common and proteinuria and hematuria can occur.

Acute Leukemia Test

1. Most patients with peripheral blood routines have an increased WBC. WBC <1.0 × 10 ⁹ / L is called leukopenia, and WBC> 10 × 10 ⁹ / L is called leukopenia. Called high leukemia. Peripheral blood smears show primitive or naive cells. Most patients may be accompanied by varying degrees of anemia and thrombocytopenia.

2. Bone marrow morphological examination of bone marrow cells is the basis for the diagnosis of AL. Primitive cells account for 30% of all bone marrow nucleated cells (FBA typing standard) or 20% (WHO typing standard). Auer's bodies are found in AML and not in ALL. Combined with cell histochemical staining, AL can be further classified and typed.

3. Cellular immune phenotype The source of leukemia cells is determined based on a series of related antigens expressed by leukemia cells.

4. Cytogenetics and molecular biology chromosomal abnormalities are found in more than half of patients with AL. The most common chromosomal abnormalities in AML are t (8; 21), t (15; 17), inv (16), +8, +21, etc .; the most common in adult ALL is the Ph chromosome. APL patients can detect PML / RAR fusion genes.

5. According to different cases, it can be used for routine urine, stool routine, chest X-ray examination, ECG, liver function, kidney function, HBSAG, immune function and other items. Coagulation tests can have varying degrees of abnormality and even evidence of DIC.

Diagnosis of acute leukemia

Clinical manifestation

He has symptoms of anemia, bleeding, fever, infection, and infiltration of leukemia cells, such as enlarged liver, spleen, and lymph nodes, and sternal tenderness.

Blood image

The number of white blood cells can be high or low, and there are different numbers of primitive and naive cells in classification. Red blood cells and platelets can be reduced to varying degrees.

3. Myeloid

Hyperplasia grade , the number of primitive cells in the classification increased significantly, at least> 30% (FAB diagnostic criteria) or 20% (WHO diagnostic criteria). Auer's bodies are visible in AML.

4. Cellular immunophenotype, cytogenetic examination and molecular genetic examination

Based on clinical manifestations, peripheral blood and bone marrow cytology, a preliminary diagnosis of AL can be made. Based on the initial diagnosis of the patient, the cytogenetics, cellular immunology, and molecular biology (ie, MICM) examinations should be improved as much as possible to make a more accurate diagnosis to comprehensively judge the patient's prognosis, perform risk stratification and Develop a corresponding treatment plan.

Acute Leukemia Treatment

The general treatment principle is to eliminate as many leukemia cell populations as possible and control the massive proliferation of leukemia cells, and to relieve various clinical manifestations caused by infiltration of leukemia cells in order to achieve complete remission.

Supportive treatment

(1) Pay attention to rest when you have high fever, severe anemia or obvious bleeding. Eat high-calorie, high-protein foods to maintain water and electrolyte balance.

(2) Prevention and control of infections Severe infections are the main cause of death, so prevention and control of infections are very important. A "sterile" ward or area should be set up in the ward to isolate people with low neutrophil counts or those undergoing chemotherapy. Pay attention to the hygiene of the skin around the mouth, nasopharynx, and anus to prevent mucosal ulcers, erosions, and bleeding, and treat them promptly when they occur. Food and utensils should be sterilized first. Oral non-absorbable antibiotics such as gentamicin, colistin and antimycotics such as nystatin, vancomycin, etc. to kill or reduce intestinal bacteria and mold. For patients with existing infections, perform bacterial culture and drug sensitivity tests before treatment in order to choose effective antibiotic treatment.

(3) Those who have corrected anemia and marked anemia can transfusion red blood cells or fresh whole blood as appropriate; for autoimmune anemia, adrenocortical hormone, testosterone propionate or anabolic hormone can be used.

(4) Control of bleeding Chemotherapy for leukemia to relieve the disease is the most effective way to correct bleeding. However, thrombocytopenia and bleeding are likely to occur before chemotherapy is relieved. Hemostatic drugs such as Anluoxue can be used for prevention or treatment. When there is severe bleeding, use adrenocortical hormone, platelet transfusion, plasma, etc. Acute leukemia (especially promyelocytic leukemia) is prone to DIC (acute disseminated intravascular coagulation). Once diagnosed, heparin should be quickly treated with anticoagulation. When DIC is accompanied by hyperfibrinolysis, it should be given at the same time as heparin treatment. Antifibrinolytic drugs. If necessary, fresh or frozen plasma can be transfused.

(5) Prevention and treatment of hyperuricemia. Patients with high white blood cell counts may have a large number of white blood cells destroyed and broken down during chemotherapy, which may increase blood uric acid, sometimes cause urinary tract obstruction by uric acid stones, and even cause acute renal failure Therefore, pay special attention to urine output, and check urine sediment and determine uric acid concentration. In addition to encouraging patients to drink more water, purine alcohol should be given.

(6) Treatment of hyperleukemia When WBC> 100 × 10 ⁹ / L, white blood cell stasis may occur, and it should be treated urgently to reduce various complications caused by it. WBC can be eliminated by blood cell separation technology (except APL); WBC can also be reduced with drugs, hydroxyurea for AML, dexamethasone for ALL, and comprehensive treatment measures such as hydration and alkalization.

2. chemotherapy

Chemotherapy is the main method for treating acute leukemia. Chemotherapy can be divided into two phases of induction remission treatment and post-remission treatment, during which intensive treatment, consolidation treatment and central nervous system preventive treatment can be added.

Remission induction is a strong chemotherapy combined with large doses of multiple drugs, in order to quickly kill a large number of leukemia cells, control the disease, achieve complete remission, and lay a foundation for future treatment. The so-called complete remission refers to the symptoms of leukemia, the signs of which have completely disappeared, and the blood and bone marrow images have basically returned to normal. The purpose of post-remission treatment is to consolidate treatment and maintain intensive treatment, and finally to cure the disease. Consolidation treatment is performed after patients with induction remission receive remission. In principle, the original induction chemotherapy regimen is used to continue for 1 to 2 courses. Maintenance consolidation therapy is performed after induction remission therapy has achieved complete remission of patients and after consolidation therapy, in order to continue to kill the remaining leukemia cells in the body in the maximum amount. Central nervous system preventive treatment should be performed immediately after remission of induction therapy to avoid and reduce the occurrence of central nervous system leukemia. A complete treatment plan should follow the above principles.

3. Bone marrow transplant

(1) The donor of the same gene bone marrow transplantation is the identical twin.

(2) The donor of allogeneic bone marrow transplantation is the patient's sibling or unrelated donor.

(3) Autologous bone marrow transplantation does not require the selection of donors and is easy to promote.

(4) Peripheral blood hematopoietic stem cells and cord blood transplantation can have both autologous and allogeneic donor sources.