What is leukemia? Get it and die? Can it be prevented?

Leukemia is a malignant disease of white blood cells in human blood. There are a large number of abnormal leukemia cells in blood, bone marrow and various tissues and organs of patients with this disease. These cells proliferate continuously, and patients may have a series of symptoms, because different types of white blood cells have different clinical manifestations. According to the maturity of white blood cells, leukemia can be divided into acute and chronic types. In acute leukemia, almost all patients' leukemia cells are immature and naive. Taking granulocytes as an example, most of them are primary granulocytes and promyelocytes, with advanced promyelocytes as the main ones. What needs to be explained here is that chronic leukemia does not evolve from acute leukemia. According to the different types of white blood cells, they can be divided into lymphocyte type, granulocyte type, monocyte type, plasma cell type and megakaryocyte type, and sometimes they can be mixed by two kinds of cells, such as granulocyte-monocytic leukemia.

Leukemia is a malignant tumor of hematopoietic system. It is characterized by malignant tumor of one or more blood cell components in hematopoietic system such as bone marrow and lymph nodes, which infiltrates various organs and tissues in the body, resulting in inhibition of normal hematopoietic cells and various symptoms. Leukemia usually manifests as fever, hemorrhage, anemia and enlargement of liver, spleen and lymph nodes. Leukemia is generally divided into acute and chronic according to the natural course of disease and the degree of cell infantility, and into granulocyte, lymphocyte, monocyte and other types according to the cell type. The clinical manifestations are different. Most of them can be relieved by traditional Chinese medicine and chemotherapy, and some of them can survive or even be cured for a long time.

Leukemia is one of the common tumors, accounting for the sixth place in tumor incidence, accounting for about 3-4/65438+ 10,000 people, of which acute is more than chronic, and acute patients account for more than 70%, among which acute granulocytes are the first, followed by acute lymphoblastic leukemia and acute leukemia. Chronic leukemia is more common in China.

● Etiology of leukemia

The etiology of acute leukemia is related to virus infection, chemical factors, ionizing radiation and other factors:

1. The research on virus infection in recent ten years shows that leukemia is probably caused by virus. The virus causes leukemia in birds, mice, rats, guinea pigs, cats, dogs, cows, pigs and monkeys. In addition, it is currently believed that C-RNA tumor virus is related to the etiology of human leukemia.

2. After the atomic bombs exploded in Hiroshima and Nagano, Japan, the incidence of leukemia increased significantly. The closer to the explosion center, the higher the incidence. In addition, the incidence of leukemia in the treatment group was 10 times higher than that in the control group, and the incidence was closely related to the radiation dose. Some countries report that radiologists have a higher proportion of leukemia.

3, chemical factors Some chemicals such as benzene and chloramphenicol can also induce leukemia by damaging bone marrow. Acute leukemia may be related to oral chloramphenicol. Others include aminopyrine, sulfanilamide, phenylbutazone, 223, dimethoate and so on.

4. According to the literature of genetic factors, the incidence of leukemia in patients with congenital dementia is 15-20 times higher than that in normal children; Patients with other congenital diseases with chromosomal abnormalities (such as Bloom syndrome, Fanconi syndrome and Klinefelter syndrome) also have a high incidence of leukemia. There are a few familial and congenital leukemia.

● Classification

Leukemia can be divided into acute and chronic types according to the degree of cell differentiation and the length of natural course, and then into several types according to cell types. For example, acute leukemia is divided into acute lymphoblastic leukemia and acute non-lymphocytic leukemia. Referring to the FAB classification proposed by hematologists in France, the United States and Britain, China proposes the following classification:

1. Common leukemia

(1) lymphocytic acute leukemia:

① type ⅰ (l1);

② Type Ⅱ (L2);

③ Type Ⅲ (L3).

Nonlymphocytic type:

① Myeloid leukemia: undifferentiated type (m1);

② Myeloid leukemia: partial differentiation (m2);

③ Promyelocytic leukemia with increased granules (m3);

④ Myeloid-monocytic leukemia (M4);

⑤ Monocytic leukemia (M5);

⑥ Erythroleukemia (M6);

⑦ Megakaryocytic leukemia (M,).

(2) Chronic leukemia

① Lymphoblastic leukemia;

② Myeloid leukemia;

③ Myeloid-monocytic leukemia;

④ Monocytic leukemia.

2. Special type of leukemia

(1) Hypoproliferative leukemia;

(2) lymphosarcoma leukemia;

(3) histiocytic (reticular) sarcoma leukemia;

(4) plasma cell leukemia;

(5) Polychromatic leukemia;

(6) eosinophilic leukemia;

(7) basophilic leukemia;

(8) Acute leukemia, etc.

Acute lymphoblastic leukemia is the main disease in childhood, accounting for more than 75% of childhood leukemia. Acute non-lymphocytic leukemia accounts for about 20% ~ 25%; Chronic only accounts for about 3% ~ 5%.

In addition to the above morphological classification, we can also combine immunology and cytogenetics for typing, that is, MIC typing.

Leukemia treatment

With the development and progress of medicine, the treatment level of acute leukemia has also been greatly improved. People are not only satisfied with the complete remission of patients, but also committed to the study of making patients survive or even recover for a long time. At present, the treatment methods of leukemia include chemotherapy, integrated traditional Chinese and western medicine, bone marrow transplantation, biological regulator therapy, gene therapy and so on.

● First, chemotherapy

June 1946 1 case of leukemia treated with chemotherapy drugs was relieved, which opened a new era of leukemia treatment. Since 1970s, the strategy of combined chemotherapy, maintenance and consolidation therapy has been gradually improved. In recent years, with the application of new anti-leukemia drugs, the curative effect of leukemia has made great progress. The latest research results show that the complete remission rate of all in children has reached 85%-95%. The 5-year disease-free survival rate is ≥50%-70%. The complete remission rate of adult ALL is close to 75%-85%. The 5-year disease-free survival time is ≥40%-50%, and the CR rate of adult acute myeloid leukemia is 65%-85%. The long-term disease-free survival rate under 60 years old can reach 40%-50%. With the development of leukemia treatment research, the curative effect is still improving. It brings hope for the radical cure of leukemia. In order to achieve this goal, we must integrate modern treatment methods according to the different characteristics of each patient, fully realize that the treatment of leukemia is a whole, and especially analyze and understand the characteristics of each patient, such as age, gender, leukemia type, hematological characteristics, cytogenetics and molecular biology characteristics, and cell dynamics of leukemia cells. On this basis, we should design the best treatment plan for patients, make rational use of modern treatment methods, such as chemotherapy, hematopoietic stem cell transplantation, biological and gene therapy, and combination of traditional Chinese and western medicine, and cooperate and coordinate with each other to avoid all kinds of toxic and side effects as much as possible. Kill leukemia cells, so that patients can achieve the purpose of long-term survival and even cure.

Chemotherapy is generally divided into induction remission therapy (chemotherapy in which the initial treatment of leukemia reaches CR); Consolidation therapy (chemotherapy similar to induction therapy after CR); Maintenance therapy (chemotherapy with weaker intensity and less bone marrow suppression than induction chemotherapy); Intensive therapy (referring to chemotherapy that is stronger than induction therapy) is divided into early intensive and late intensive.

The important principles of chemotherapy are early, sufficient, combined and individualized treatment. The increase of chemotherapy dose and intensity is one of the main factors to improve the CR rate and long-term survival rate of leukemia patients. Morphological classification of bone marrow in leukemia patients with CR, although leukemia cells

Since 1980s, chemotherapy for leukemia has mostly adopted combined chemotherapy, focusing on cell cycle and sequential medication. Generally, a variety of drugs that act on different cell cycles and can mutually promote and enhance the ability to kill leukemia cells, but have different or reduced toxic and side effects and relatively selectively kill leukemia cells are selected for combined chemotherapy.

The individualized principle of leukemia chemotherapy is the development of leukemia treatment research, which emphasizes four aspects: ① Choose different chemotherapy schemes for different types of leukemia, and choose different drugs, doses and courses of treatment for everyone. ② For leukemia individuals with different prognostic factors, the treatment plan should be different. For example, for T-ALL and B-ALL, in addition to routine treatment, adding CTX or MTX and cytarabine can obviously improve their CR rate and survival time. ③ The health status of patients before chemotherapy is also a problem that needs to be considered in individualized chemotherapy. Patients with liver, kidney and heart dysfunction should reduce chemotherapy drugs. ④ Closely observe the changes of patients' hemogram and bone marrow image during chemotherapy, and increase or decrease the chemotherapy dose in time according to different situations.

Causes of failure of chemotherapy for leukemia: The failure of chemotherapy is mainly due to premature death caused by infection and bleeding during chemotherapy, or leukemia cells are drug-resistant and ineffective. Generally, there are several cases of failure: ① leukemia cells are completely drug-resistant, which shows that bone marrow proliferation is inhibited after chemotherapy but leukemia cells are not reduced; ② Leukemia cells were partially drug-resistant, indicating that leukemia cells were partially reduced after chemotherapy, but it was not ideal, and then leukemia cells proliferated again; ③ After 4 weeks of chemotherapy, the abnormal bone marrow did not recover; ④ Bone marrow dysplasia and death within four weeks; ⑤ Early death due to uncontrollable bleeding and infection during chemotherapy; ⑥ CR but extramedullary leukemia exists after chemotherapy. There are still a few patients whose leukemia cells decrease rapidly after chemotherapy, and their bone marrow and hemogram are also suppressed rapidly, but soon leukemia cells and WBC multiply rapidly and their condition deteriorates rapidly. Such patients are difficult to treat, with poor prognosis and lack of effective treatment methods.

Second, integrated traditional Chinese and western medicine treatment.

The combination of traditional Chinese and western medicine can complement each other. Traditional Chinese medicine can make up for the deficiency of western medicine in chemotherapy and solve the problem of drug resistance. At the same time, some low-proliferative leukemia, with low white blood cells and platelets, can not stand strong chemotherapy drugs, and can be treated with traditional Chinese medicine, which not only avoids the toxic side effects of western medicine, but also alleviates the condition. The combination of traditional Chinese and western medicine has the following forms.

1. Simple Chinese medicine treatment, suitable for hypoproliferative leukemia, can not tolerate chemotherapy, can use Chinese medicine. Then, those patients who have never used chemotherapy drugs in the early stage of the disease and have not yet developed drug resistance can use traditional Chinese medicine, which is suitable for patients with low immature cells. Take medicine every day, and after a period of time (usually 3-4 months), CR can be reached. In the treatment of this disease, our hospital put forward a series of drug combinations to effectively control the growth of leukemia cells, make them gradually transform and decompose, and kill some leukemia cells at the same time, thus regulating human immunity, improving human metabolism and discharging toxins. Through the above-mentioned overall regulation and targeted comprehensive effects on the human body, the purpose of curing leukemia is achieved. Chinese medicine has brought us the dawn of treating leukemia.

2. Combination of traditional Chinese and western medicine, that is, after chemotherapy, traditional Chinese medicine is used to strengthen the body. Thereby improving white blood cells and platelets, enhancing human immune function and resisting infection. To stop bleeding, traditional Chinese medicine can still be used in the remission stage of chemotherapy. One is to promote human recovery, and the other is to consolidate the effect of chemotherapy and delay the next chemotherapy.

3. Chinese patent medicine prescription

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Hassie Huang Xi pills, two bottles twice a day.

The Tibetan medicine "Mangjiao" takes one pill twice a day.

Third, biological regulator therapy.

With the development of immunology and gene technology, biological regulator therapy has been applied in clinic, including interleukin -II, various hematopoietic stimulating factors such as GM-CSF, G-CSF, M-GCSF erythropoietin, swelling and pain necrosis factor, interferon and so on. It has been proved that interleukin -II, LAK cells and so on. It has certain curative effect on leukemia, G-CSF and GM-CSF. It can obviously shorten the inhibition of bone marrow and hemogram after chemotherapy.

Fourth, gene therapy.

Gene therapy is to introduce foreign genes into target cells (tissues) to correct, compensate or inhibit some abnormal or defective genes, so as to achieve therapeutic purposes. Treatment methods can be divided into four categories: ① gene compensation: transferring genes with normal functions into target cells to compensate for deletion or inactivation. ② Gene modification: the abnormal genes of the original drug were eliminated and replaced by foreign genes. ③ Gene compensation: The expression level of exogenous normal genes exceeded the abnormal gene expression level of the original drug. (4) Antisense technology: The specific complementary DNA or RNA fragments synthesized artificially or biologically or chemically modified products are used to inhibit or block abnormal or missing gene expression.

As a new method, leukemia gene therapy is gradually transitioning from theoretical research to clinical trials. Has passed the second phase of clinical trials in the United States. At present, antisense oligonucleotides are mainly used to block proto-oncogenes in gene therapy. Antisense technology can treat the target substance and its products without changing the gene structure. So it is the simplest and clearest means of gene therapy. At present, CML is the leukemia with the most antisense nucleic acid technology. By improving the existing technology and using a variety of antisense DNA/RNA and helper gene systems including BCR/ABL fusion gene, it is expected to make a breakthrough in gene therapy of CML in the near future.

Five, bone marrow transplantation (BMT)

Allo-BMT (Allo-BMT) is a therapeutic method to treat patients with ultra-high dose radiotherapy and chemotherapy, and then implant hematopoietic stem cells from healthy bone marrow into patients to rebuild their hematopoietic and immune functions.

The treatment of diseases with bone marrow began in 189 1 year when Brown-seqard gave patients bone marrow orally to treat anemia, and it began in 1939 when Osgood infused bone marrow intravenously for the first time, and in 195 1 year when Lorenz successfully conducted the first bone marrow transplant experiment, which began in the 1970s. In recent years, there have been more than 300 cases of allogeneic BMT in China, and the curative effect has basically reached the international level.

The long-term disease-free survival rate of allogeneic BMT for leukemia is about 50%. According to the statistics of International BMT Registration Center 1993, the five-year survival rate of BMT in the treatment of leukemia is about 50% in the first complete remission period of ALL (CR 1), about 32% in the second complete remission period of ALL (CR2) or above, and about 18% in the recurrence period of ALL. CR2 or >; CR2 is about 35%, chronic myeloid leukemia (CML) is about 45%, accelerated phase is about 36%, and acute phase is about 6%. It can be seen that leukemia patients should be treated with BMT as soon as possible after CR chemotherapy.

There are two main risks in BMT treatment: one is that BMT has many transplant-related complications, and the other is that there is still the problem of leukemia recurrence after BMT. The main transplant-related complications were hepatic vein occlusion, with an incidence of 25% and a mortality of 80%, and graft-versus-host disease, with an incidence of 10%-80%. The recurrence rate of leukemia after BMT is about 15%-30%.

Steps of Arlo BMT:

1) Select the donors whose HLA (human leukocyte antigen) is completely consistent. The selection order is that the HLA genotypes of siblings are consistent, followed by family members with consistent HLA phenotypes, then a family member with incompatible HLA loci or an unrelated donor with compatible HLA phenotypes, and finally select an unrelated donor with incompatible HLA loci or two or three family members with incompatible HLA loci.

2) For the preparation of recipients, the diagnosis and typing of leukemia should be verified and confirmed. The general age should be limited to 45-50 years old, and the functions of important organs are basically normal. It is necessary to clear all kinds of infected lesions in the body, carry out comprehensive experience and necessary examinations, and generally there are more than a dozen auxiliary examinations. The recipient was admitted to the aseptic laminar flow ward one week in advance.

3) Matching histocompatibility antigen and gene.

4)BMT pretreatment should last for three months. Firstly, the original hematopoietic cells in the recipient are destroyed to prepare the growth space for the implanted hematopoietic stem cells. The second is to inhibit the immune cells and functions in the recipient, which is beneficial to bone marrow implantation. The third is to eliminate and kill a large number of leukemia cells in the recipient.

5) Collection, treatment and infusion of bone marrow: The donor's bone marrow was collected in the operating room under aseptic conditions on the day of bone marrow infusion, filtered and infused to the recipient by vein as soon as possible to avoid the loss of hematopoietic stem cells. Bone marrow with ABO blood group incompatibility should be treated before blood transfusion.

6) Nutrition and supportive treatment often needed during 6)BMT.

7) Early prevention and treatment of BMT complications, elimination of digestive tract toxic reactions, control of multiple infections, bleeding and other major complications.

8) Prevention and treatment of late complications of BMT, such as chronic graft-versus-host disease.

9) Evidence of 9)BMT hematopoietic reconstruction and transplantation. After BMT, patients have to go through the process of failure of the original hematopoietic system and hematopoietic reconstruction with newly implanted bone marrow. The gradual increase of reticulocytes after BMT is considered as an early indicator of bone marrow transplantation. It usually takes 3-6 months for the peripheral blood picture to return to normal. In addition, the detection of red blood cell antigen and white blood cell antigen and cytogenetic analysis can directly prove whether BMT implantation is successful.

10) Leukemia recurs after BMT. Generally speaking, the recurrence rate is high in the elderly, those who are not completely relieved for the first time and those who are not in chronic phase of CML, and those who are pretreated with low dose TBI (total body irradiation) by BMT have a high recurrence rate, mostly (95%) in the recipients. The main reason for recurrence is that leukemia cells were not completely eliminated during BMT, that is, there were more leukemia cells left in the body after BMT, and the anti-leukemia effect of the graft was weak.

2. Autologous stem cell transplantation and cord blood hematopoietic stem cell transplantation

The so-called "autologous stem cell transplantation" refers to the collection of autologous hematopoietic stem cells before high-dose radiotherapy and chemotherapy to protect them from the damage of high-dose radiotherapy and chemotherapy, and then reinfusion after high-dose radiotherapy and chemotherapy. Autologous hematopoietic stem cells can be derived from bone marrow or collected from peripheral blood of patients. Autologous stem cell transplantation can be used for elderly patients due to complications such as graft-versus-host disease. The steps are as follows: after collecting hematopoietic stem cells, they are stored at above zero and below zero respectively, and then thawed and reinfused. Before transplantation, autologous stem cells and residual white blood cells need to be purified first. Patients were given necessary examination, radiotherapy and chemotherapy pretreatment, and support treatment such as controlling infection and bleeding after transplantation. Autologous stem cell transplantation is superior to conventional chemotherapy. It is reported that it is one of the effective consolidation treatment measures for acute leukemia after CR. Its disadvantage is high recurrence rate, and there is no unified statement on its survival time and reason.

Umbilical cord blood hematopoietic stem cell transplantation was the first case in the world in 1988. Since then, many scholars have devoted themselves to this research. Compared with BMT, the implantation time of umbilical cord blood transplantation is slightly wrong. Second, the incidence of severe GVHD after transplantation is low when HLA matching is mismatched at 1-2 sites. Third, hematopoietic factors have little effect on implantation. Fourth, the number of umbilical cord blood cells is limited, so it is not appropriate to limit the weight too much (

At present, the exact cause of leukemia is not very clear, but a lot of scientific research shows that radiation, some chemicals, viruses and genetic factors can induce leukemia. Gamma rays, X-rays and other radiation are invisible radiation emitted by radioactive substances, and a large number or several exposures to radiation will lead to leukemia. It should be explained here that when we go to the hospital for filming, the fluoroscopy and radiation dose are very small and will not cause leukemia. Many chemicals are harmful to hematopoietic system, and some can induce leukemia. Here are some specific chemicals and drugs, such as benzene and its derivatives, gasoline, paint, hair dye (including aniline), etc. Drugs cause diseases such as chloramphenicol and phenylbutazone, and alkylating agents for some cancers can cause leukemia. It has been recognized that viruses can cause leukemia. For example, human T lymphocytes infected with viruses (types I and II) can cause leukemia. People infected with this virus will not get leukemia immediately, only if there are some risk factors. These risk factors are radiation, chemicals and certain drugs. Repeated exposure to a large number of viruses, decreased immune function and the age of patients are all dangerous "catalytic" factors. The etiology of leukemia is related to genetic factors. Heredity here does not mean that parents' diseases can be passed on to their children, but that the incidence of leukemia with abnormal chromosomes and genes is significantly higher than that of normal people. For example, the existence of PH and chromosome is closely related to the pathogenesis of chronic myeloid leukemia. Among the twins, one suffers from leukemia and the other is at great risk.

Prevention of leukemia

● How to prevent leukemia

Although the etiology of leukemia has not been completely clarified, it has been found that the occurrence of leukemia may be related to the following factors:

① radiation;

② Certain drugs or chemicals;

③ Type C virus;

④ Genetic factors.

Leukemia, like other cancers, can't be completely prevented, but it can also be relatively prevented according to some pathogenic factors.

First of all, don't be too exposed to X-rays and other harmful radiation. Personnel engaged in radiation work should do personal protection and strengthen preventive measures. Babies and pregnant women are sensitive to radiation and vulnerable. Women should avoid too much radiation during pregnancy, otherwise the probability of fetal leukemia is high. However, the occasional medical X-ray examination, the dose is very small, basically will not affect the body.

Secondly, don't abuse drugs. When using chloramphenicol, cytotoxic anticancer drugs, immunosuppressants and other drugs, be cautious, be sure to have the guidance of a doctor, and don't use or abuse them for a long time.

Third, reduce exposure to benzene. Chronic benzene poisoning mainly damages the hematopoietic system of human body, causes the decrease of white blood cells and platelets, and induces leukemia. Workers engaged in the production of benzene as chemical raw materials must pay attention to strengthening labor protection.