Leukemia is aHematopoietic stem cellsThe complex pathogenesis of malignant clonal diseases is associated with many factors such as biology, physics, chemistry, genetics and other blood diseases.amongbone marrowThe proliferation of leukemia cells in other hematopoietic tissues is out of control, resulting in inhibition of normal hematopoiesis and exudation to other organs.In China, the incidence of leukemia is 3-5 per 100000 people, of whichAcute myeloid leukemiaMost common, andacute leukemiaAndChronic leukemiaThe incidence of acute myeloid leukemia is more common in adults than in childrenacute lymphoblastic leukemiaSee more.
According to the clinical symptoms, the severity of the disease varies and the typical symptoms are not obvious compared with common diseases in the early stage.Acute leukemia may have high fever or severe bleeding, but the chronic progress is relatively slow. It may have anemia and bleeding symptoms, swollen lymph nodes and spleen, and abnormal proliferation of lymphocytes.Leukemia is non infectious, virus infection, abnormal immune function, long-term exposure to physical and chemical factors, bad living habits, and even cancer treatment are common incentives.
There are several treatments for leukemia, including molecular targeted drug therapychemotherapy、radiotherapy, blood or bone marrow transplantation and adjuvant therapy for various symptoms.The prognosis after treatment varies from person to person. For some patients, long-term survival or cure can be achieved through appropriate treatment, and some patients may relapse or progress.In terms of prevention, as the specific pathogenesis has not yet been clarified, there is no specific preventive measures at present, and only limited prevention can be carried out by avoiding exposure to known risk factors.
The latest research results of leukemia are reflected in the individualized treatment scheme for specific types of leukemia, such as tyrosine kinase inhibitors, which have significant effects on chronic myeloid leukemia with specific gene mutations.These latest studies have brought new hope for the future treatment of leukemia.
TCM disease name
leukemia
Visiting department
Department of Hematology
Multiple population
Children and adults under 35
Common location
Bone marrow and other hematopoietic tissues
Common causes
Related to biological factors, physical factors, chemical factors, genetic factors and other blood diseases
common symptom
Fever, anemia, bleeding, bone pain, enlargement of liver and spleen lymph nodes, weight loss
According to the degree of cell differentiation and maturity and the natural course of disease, it can be divided intoacute leukemia(acute leukemia, AL) andChronic leukemia(chronic leukemia, CL).Among them, the cell differentiation of AL stagnates in the early stage, most of which are primitive cells and early immature cells. The disease develops rapidly, and the natural course of the disease is only a few months.The differentiation of CL cells stagnated at a later stage, most of which were mature cells and mature cells. The disease was relatively slow, and the natural course of the disease was several years.
According to the cell series mainly involved, it can be divided into lymphocytic leukemia and non lymphocytic (myeloid) leukemia.AL can be divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). CL can be divided into chronic myeloid leukemia (CML), chronic lymphocytic leukemia,CLL) and rare types of leukemia, such as hair cell leukemia, lymphoblastic leukemia, etc.
acute lymphoblastic leukemia
staybone marrowandlymphoid tissueIt is characterized by abnormal proliferation and aggregation of immature lymphocytes.It is mostly found in children.
Acute myeloid leukemia
Also called acute non lymphocytic leukemia, it is a leukemia in which hematopoietic cells other than lymphocytes have abnormal clones, such as myeloid leukemia, erythroleukemia, and megakaryocytic leukemia.It is the most common type of acute leukemia in adult patients.In addition, acute promyelocytic leukemia is a special type of acute myeloid leukemia, which is easily seen in young and middle-aged people.
Chronic lymphocytic leukemia
It is characterized by the aggregation of mature B lymphocytes in the peripheral blood, bone marrow, spleen and lymph nodes, mainly in middle-aged and elderly people.
Chronic myeloid leukemia
The abnormal increase of normal peripheral blood leukocytes is characterized by the increase of intermediate late neutrophils and mature granulocytes, eosinophils and basophils.More than 95% of patients have Philadelphia chromosome (Ph chromosome).
pathogeny
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The etiology of leukemia is not completely clear, and current research shows that it may be related to biological factors, physical factors, chemical factors, genetic factors and other blood diseases.
Pathogenesis
The occurrence of leukemia may be multi-step. At present, it is believed that at least two types of molecular events are involved in the pathogenesis.
First, some gene mutations in hematopoietic cells caused by various reasons activate a certain signal pathway, leading to clonal abnormal hematopoietic cell generation. Such cells gain proliferation and (or) survival advantages, and most of them are blocked by apoptosis;
Second, some genetic changes may involve some transcription factors, resulting in the retardation or disorder of hematopoietic cell differentiation.
Predisposing factors
viral infection
After the virus infects the body,Adult T-cell leukemia/lymphoma(ATL) can be caused by human T-lymphocyte virus type I.As an endogenous virus, it lurks in the host cell and is activated by some factors to induce leukemia;Or as an exogenous virus to spread infection and directly cause disease.
Abnormal immune function
Some patients with abnormal immune function, such as some patients with autoimmune diseases, have a higher risk of leukemia.
Physical factors
MainlyX-ray、Gamma rayIsoionizing radiation.Studies have shown that large-area and high-dose irradiation can inhibit bone marrow and reduce immunity, DNA mutation, breakage and recombination, leading to leukemia.
Chemical factors
Years of exposure to benzene and organic solvents containing benzene can cause leukemia.Ethbimorphine is a derivative of ethylimine, which can cause chromosome aberration and leukemia.In addition, some antineoplastic drugs (such asAlkylating agentEtc.) can also cause leukemia.
Genetic factor
Family history of leukemia may increase the risk of disease.Familial leukemia accounts for 0.7% of leukemia. There are Down's syndrome, congenital aplastic anemia, dwarf face telangiectasia (Bloom syndrome), ataxia telangiectasia, congenital immunoglobulin deficiency and other genetic diseases. The incidence of leukemia is high.
Those who have bad living habits such as smoking, drinking, drug taking, irregular work and rest are easy to induce.
Cancer treatment
Other cancer patients are also prone to increase the incidence of leukemia when receiving chemotherapy and radiotherapy.
symptom
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The onset of leukemia is different, and the clinical manifestations of acute leukemia and chronic leukemia are different.
Typical symptoms
early symptom
Acute leukemia may have sudden high fever, similar to "cold" symptoms, or severe bleeding;Chronic leukemia generally progresses slowly, and patients may have pale complexion, swollen lymph nodes and spleen, excessive menstruation or bleeding after tooth extraction.
acute leukemia
anemia
Most patients have moderate to severe anemia at the time of treatment. Some patients with acute leukemia have a short course of disease, but no anemia.
Fever and infection
Fever is the early manifestation of half of the patients, which can be low or as high as 39 ℃~40 ℃.Hyperpyrexia often indicates secondary infection, which may occur in various parts of the body, such as gums, perianal, lungs, etc., and sepsis may occur in severe cases.
hemorrhage
Early bleeding was nearly 40%.It can occur in all parts of the body, with skin ecchymosis, epistaxis, gingival bleeding, and menorrhagia.Intracranial hemorrhage, gastrointestinal hemorrhage and urinary system hemorrhage are rare, but the consequences are serious.
Expression of proliferation and infiltration of leukemia cells
Lymph node and splenomegaly: Lymph node enlargement is a significant feature of lymphocytic leukemia, which is more common in acute lymphocytic leukemia.Spleen enlargement is more common in acute leukemia.
Bone and joint pain: Bone pain is one of the common signs of leukemia, which is often severe and unfixed, mainly seen in the sternum, limb bones, spine and pelvis.The use of painkillers is not effective.Children are more common than adults.
Eye: Some leukemia may cause exophthalmos, diplopia or blindness.
Oral cavity and skin: common in acute leukemia, manifested as gingival hyperplasia, swelling or bleeding.Local skin bulges and hardens, showing purplish blue nodules.
Central nervous system: it can affect the circulation of cerebrospinal fluid, causing increased intracranial pressure, headache, nausea, vomiting, blurred vision, papilledema, even convulsions, coma and other manifestations.
Testis: most of the testes are painless enlargement on one side and no enlargement on the other side, but leukemia cell infiltration is often found during biopsy.
The chronic phase of chronic myeloid leukemia generally lasts for 1-4 years, and patients have symptoms of hypermetabolism such as fatigue, low fever, sweating or night sweating, weight loss, etc.Spleen enlargement is the most obvious sign. If the spleen is infarcted, the tenderness in the spleen area is obvious.When the white blood cells are significantly increased, there may be eyeground congestion and bleeding.During the disease acceleration period, there are often fever, weakness, progressive weight loss, bone pain, and gradually anemia and bleeding. The acceleration period can last for months to years.When acute myeloid leukemia enters the acute transformation period, the prognosis is poor, and it often dies within a few months.
Chronic lymphocytic leukemia.The onset of the disease is slow, and most patients have no conscious symptoms. Most patients find it during physical examination or medical treatment due to other diseases.Symptomatic patients may show fatigue and fatigue in the early stage, and then have anorexia, emaciation, low fever, night sweats, etc.60%~80% of the patients have lymph node enlargement, mostly in the head and neck, clavicle and other places.More than half of the patients have mild to moderate splenomegaly, mild hepatomegaly and other symptoms.Anemia, thrombocytopenia and granulocytopenia may occur in patients with advanced stage, and they are often complicated with infection.
Accompanying symptoms
Leukemia cells can also infiltrate the respiratory, digestive and urogenital systems, and may have diffuse or nodular changes in the lungs, accompanied by pleural effusion, digestive disordersproteinuria, hematuria, amenorrhea and other symptoms.In patients with severe central nervous system leukemia (CNSL), facial paralysis and progressive paraplegia can also be seen.
Medical treatment
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Leukemia symptoms are usually atypical, and early symptoms are similar to influenza and other common diseases, which are often ignored.When patients have fever, anemia, bleeding, bone pain, hepatosplenic lymph node enlargement, weight loss and other symptoms, they should seek medical advice in a timely manner.
Diagnostic basis
According to clinical manifestations and blood routine tests, doctors can often make a preliminary diagnosis.conductBone marrow punctureAfter, getMyelogramIt can be confirmed.
Visiting department
Department of Hematology.
Relevant inspection
routine blood test
The examination showed abnormal levels of platelets, white blood cells, white blood cell ratio or count, and the classification of white blood cells showed primitive and immature cells.
Blood biochemical examination
Leukemia, especially during chemotherapy, may have elevated transaminase, serum uric acid concentration, uric acid excretion, and serum lactate dehydrogenase.
Bone marrow biopsy
Bone marrow samples were taken from ilium, etc., and leukemia cells were found through laboratory tests.And through the characteristics of leukemia cells, typing, to determine the future treatment plan.
Cytochemical staining
Cytochemical staining is an important part of morphological diagnosis, which can be used to differentiate acute myeloid leukemia and acute lymphoblastic leukemia.
Immunotyping
Flow cytometry was used to detect the characteristic antigen expression pattern of leukemia cells through a variety of specific antibodies on bone marrow or peripheral blood samples of patients, so as to identify the origin of leukemia cells and determine their unique phenotype.It plays an important role in determining the type of leukemia, and also has important clinical value in the detection of efficacy after treatment.
Examination of chromosome karyotype and molecular biology
This test is mainly used to check the genetic abnormalities of leukemia, for diagnosis and classification and prognosis evaluation.
differential diagnosis
leukemoid
The clinical manifestations of leukemoid reaction are highly similar to those of leukemia, but there is no sternal tenderness, the spleen is not large or slightly swollen, and most of them have primary disease. The indicators and symptoms of blood abnormalities recover with the improvement of the primary disease.
Other diseases
EB virus infection, whooping cough, infectious lymphocytosis, rubella and other viral infections can also show pancytopenia.However, this kind of disease has a short course and is benign, and the number of primitive immature cells in bone marrow is not increased.Leukemia has a long course and is accompanied by an increase of primitive immature cells in bone marrow.
treatment
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The treatment of leukemia should combine the disease classification and clinical characteristics of patients to carry out prognostic risk stratification, and select the most complete and systematic treatment scheme according to the age, treatment willingness and economic ability of patients.
General treatment
acute leukemia
Emergency treatment of hyperleukaemia
High white blood cells will not only increase the mortality of patients, but also increase the recurrence rate.When the number of white blood cells in the circulating blood is more than 200 × 109/L, leukocytosis can occur.Generally, when the number of white blood cells is more than 100 × 109/L, the blood cell separator should be used urgently to collect and remove the excessive white blood cells (except for acute promyelocytic leukemia), and chemotherapy drugs and hydration and alkalization treatment should be given at the same time.
Component blood transfusion treatment
Severe anemia can cause severe hypoxia, fatigue, dizziness, chest tightness and shortness of breath after activities, and even syncope. You can take oxygen inhalation, transfusion and concentration of red blood cells, and maintain hemoglobin>80g/L.Thrombocytopenia causes bleeding, which needs to be treated by transfusion of platelet suspension.
Blood product infusion treatment
Patients with abnormal coagulation function, especially those with acute promyelocytic leukemia, can be infused with fibrinogen, prothrombin complex, plasma and other blood products to supplement needed coagulation factors and improve bleeding symptoms.
Prevention and treatment of hyperuricemic nephropathy
During chemotherapy, leukemia patients should drink more water to maintain alkaline urine. When patients have oliguria, anuria, and renal insufficiency, they should be treated as acute renal failure.
Rest and activities
Take more rest and exercise indoors according to your own conditions. Try to reduce outdoor activities to prevent infection.
nutritional support
Leukemia is a serious consumptive disease, especially when chemotherapy and radiotherapy cause gastrointestinal mucositis and dysfunction.Attention should be paid to supplement nutrition, maintain water and electrolyte balance, give patients high protein, high calorie, digestible food, and supplement nutrition intravenously when necessary.
Chronic leukemia
The treatment of chronic myeloid leukemia should focus on the early stage of the chronic phase, avoid disease transformation, and strive for remission at the level of cytogenetics and molecular biology. Once it enters the accelerated or cataclysmic phase, the prognosis will be poor.
For chronic lymphoblastic leukemia, early treatment can not prolong the survival period of patients, and early patients do not need treatment, and regular reexamination is enough.One of the following conditions indicates that the disease is highly active and treatment should be started.
Weight loss ≥ 10%, extreme fatigue, fever (38 ℃)>2 weeks, night sweat;
Progressive splenomegaly or splenic pain;
Progressive enlargement or direct enlargement of lymph nodes>10cm;
Progressive peripheral blood lymphocytes increased by more than 50% within 2 months, or the doubling time was less than 6 months;
Autoimmune hemocytopenia occurred and glucocorticoid treatment was ineffective;
Progressive bone marrow failure, anemia and (or) thrombocytopenia are progressively aggravated.
In the disease progression stage, those who have no disease progression can sometimes "observe and wait".
medication
Molecular targeted therapy
This treatment means that the drug can specifically combine with the carcinogenic site at the cellular and molecular level to cause specific death of tumor cells and reduce the side effects on normal cells.
Tyrosine kinase inhibitor
By inhibiting tyrosinase phosphorylation, blocking signal transduction, thereby inhibiting the growth and proliferation of leukemia cells.It is generally used for chronic myeloid leukemia and some acute lymphoblastic leukemia.Representative drugs include imatinib, nilotinib, dasatinib, etc.
Imatinib, the first generation tyrosine kinase inhibitor, has the advantage of early use, sufficient clinical experience and evidence, and can be selected for those with diabetes, coronary artery disease, and cerebrovascular disease history.However, some adverse reactions seriously affected the quality of life, including weight gain, fatigue, peripheral and periorbital edema, skeletal muscle pain, nausea, creatinine elevation, etc.It is recommended for first-line treatment of elderly patients.
The second generation tyrosine kinase inhibitor: the main advantage is to reduce the disease progression of high-risk patients.ECG, blood potassium and blood magnesium should be monitored when taking medicine;It should be taken on an empty stomach to avoid the increase of blood drug concentration caused by high-fat diet.Young patients can give priority to second-generation tyrosine kinase inhibitors for first-line treatment.
Immunotherapy
Rituximab
It is mainly used to treat chronic lymphoblastic leukemia. It can be used alone or combined with other chemotherapy drugs.
CAR-T cells
For example, CD19-CART and CD22-CART have achieved good results in the treatment of some acute lymphoblastic leukemia, but because of obvious adverse reactions, they need to be treated under the strict supervision of doctors.
chemotherapy
The first stage of treatment for patients with acute leukemia is induction remission treatment. Combined chemotherapy is the main method. The goal is to quickly remove a large number of leukemia cells from the patient's body. The goal of treatment is to make the patient achieve complete hematological remission.
The second stage is post remission treatment. Chemotherapy is also the main method. Hematopoietic stem cell transplantation can also be used.Common drugs includevincristine(VCR), prednisone (P), anthracycline drugs such asDaunorubicin（DNR）、Nordoxorubicin（IDA），cyclophosphamide（CTX）、Cytarabine（Ara-C）、methotrexate(MTX), 6-mercaptopurine (6-MP)Asparagine（L-ASP）。
It can be used for the prevention and treatment of central nervous system leukemia (CNSL), including craniospinal irradiation. At present, it is only used for rescue treatment of CNSL.If patients with chronic lymphoblastic leukemia have obvious lymphadenopathy or splenomegaly, and obvious local compression symptoms, radiotherapy can be considered to alleviate the symptoms when the chemotherapy effect is not ideal.
surgical treatment
Hematopoietic stem cell transplantation is still the only possible cure for acute myeloid leukemia and acute lymphoid leukemia.
TCM treatment
The TCM treatment of the disease is not supported by evidence-based medical evidence, but some TCM treatment methods or drugs can alleviate symptoms, so it is recommended to go to regular medical institutions and treat under the guidance of doctors.
prognosis
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The cure rate of leukemia is low, and the cure cycle and survival cycle are different according to different types.The course of acute leukemia develops rapidly, and the course is only a few months or even days;Chronic leukemia develops slowly and lasts for several years.
Curative
Most types of leukemia cannot be cured, and some patients with acute lymphoblastic leukemia may be cured.
cure rate
The cure rate of leukemia is low, and there is no exact data at present.
harmfulness
Because leukemic cells will be destroyed in large quantities, especially during treatment, it will cause the increase of uric acid concentration in blood, and block renal tubules, resulting in acute renal failure.
The prognosis of different types of leukemia patients is different. Most leukemia patients cannot be cured, and the course of disease is long or short, which can eventually lead to death.
Leukemia can reduce normal white blood cells, reduce immunity, and easily suffer from various serious infections, which can lead to death.
Leukemia can cause thrombocytopenia and abnormal coagulation function. In severe cases, visceral hemorrhage may often occur, such as intracranial hemorrhage, which may lead to death of patients.
complication
Infected
Patients with low cellular immune function are prone to bacterial and viral infection.Attention should be paid to personal hygiene, reasonable diet and smooth emotions.
hyperuricemic nephropathy
Due to the massive destruction of leukemic cells, especially during chemotherapy, the concentration of uric acid in serum and urine of leukemic patients increases, and accumulates inRenal tubule, causing blockingUric acid nephropathy。
scientific research
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On September 23, 2022, the first one aimed at Chinese children and adolescentscancerIncidence andAccess to health servicesThe research of current situation is in《Lancet》Journal publishing, researchDiscovery:In 2018-2020, leukemia (42.33/million) ranked first among children;Among teenagers, leukemia (30.08/million) ranks the firsttwo。
Related reports
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According to《The Guardian》On December 11, 2022, it was reported that British scientists used a revolutionary newgene therapy ——Base edited has treated a 13-year-old patient with T-cell leukemia, which is the first case in the world to apply this technology.
In January 2024, a new family pathogenic risk factor of myeloid malignant blood tumors, CTR9, was jointly found by Chinese and foreign scientists. This gene carries genetic mutations, which increases the susceptibility of blood tumors by 10 times.The study of this gene is expected to provide new ideas for the early screening and intervention of potential early-onset leukemia.
On January 13, the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences announced that Zhao Jiawei, a professor of the School of Pharmacy of Shenzhen University of Technology (preparatory), the Cancer Immunology Research Center of the Institute of Medicine of Shenzhen Advanced Institute, in conjunction with Vijay Sankaran, an outstanding associate professor of the Boston Children's Hospital affiliated to Harvard University School of Medicine and a researcher of the Broad Institute of Massachusetts Institute of Technology,The latest research results were published in Cell.
In February 2024, the US Food and Drug Administration (FDA) has approved the application for the license of supplementary biological agents for blood cancer therapy Tecvayli.
