The exact cause of former leukemia is still not very clear, but a large number of scientific studies have shown that leukemia can be induced by radiation, certain chemicals, viruses and genetic factors. Radiation such as γ-ray, X-ray, etc. is a radioactive material issued by the naked eye can not see the ray, people once a large number of or many times a small amount of exposure to radiation can lead to leukemia. It should be noted here that we go to the hospital to take pictures, fluoroscopy, radiation dose is very small will not cause leukemia. Many chemicals are harmful to the hematopoietic system and some can induce leukemia. Here is a list of some of the more certain chemicals and drugs, such as benzene and its derivatives, gasoline, paints, hair dyes (containing aniline), etc.; drugs that cause disease, such as chloramphenicol, prednisone, etc., as well as some alkylating agents used in the treatment of cancer can cause leukemia. Viruses can cause leukemia has been recognized, such as human T-lymphotropic virus (type I and type II) can cause leukemia, people infected with this virus, leukemia will not occur immediately, only when some risk factors exist to promote the development of this disease, these risk factors are radiation, chemicals and certain drugs, a large number of viruses multiple exposures, the body's immune function is reduced, as well as the patient's age, etc., is the risk of "catalytic" factors. The "catalytic" factor. The cause of leukemia is related to genetic factors, where "genetic" does not mean that the disease can be inherited from parents to their children, but refers to chromosomal and genetic abnormalities leukemia incidence is significantly higher than in normal people. For example, the presence of PH, chromosomes is very relevant to the development of chronic granulocytic leukemia. In twins, one person has leukemia and the other is at great risk.
Diagnostic criteria of chronic granulocytic leukemia
1. Clinical symptoms: the onset of the disease is slow, the early stage may not have any symptoms, the earliest symptoms of self-consciousness are often fatigue, low-grade fever, excessive sweating or night sweating, weight loss and other metabolic manifestations of hyperactivity. Splenomegaly may cause heavy discomfort in the left quarter ribs or left upper abdomen, and a feeling of fullness after eating. Because of the slow progression of symptoms, it is often months before the onset of the disease when the patient seeks medical attention. Less common symptoms include back or extremity pain, and severe pain in the left upper abdomen or left lower chest due to splenic infarction. In the advanced stage, when thrombocytopenia occurs, the skin and gums bleed easily, and women may have excessive menstruation. In patients with leukocytosis, symptoms such as blurred vision, respiratory distress, and abnormal erection of the penis are sometimes found to be induced by the "blockage" or embolization of leukocytes in the blood vessels. In these cases, the white blood cell count is often much higher than 500 × 109/L. The most prominent sign is splenomegaly, which often reaches below the level of the umbilicus at the time of the patient's first visit and is firm and non-indurated, but in the case of recent splenic infarction there is marked localized indurations and friction sounds can be heard. In the presence of anemia and splenomegaly, chronic granulomas must be differentiated from cirrhosis, schistosomiasis, and Hodgkin's disease. The liver is also often moderately enlarged, but not as dramatically as splenomegaly. The skin and mucous membranes are moderately pale. Superficial lymph nodes are not enlarged. There is often mild to moderate tenderness in the lower part of the sternum. Skin and mucosal petechiae may be present in advanced stages. Venous congestion and fatigue spots in the white heart may be present in the fundus. Painless masses (green tumors) may be present in the orbits and skull, as well as in the breasts and other soft tissues.
2. Laboratory tests
Blood: high white blood cell count above 100×109/L. Most of the blood films are neutrophilic rod-shaped nuclei and late juvenile granulocytes, and the rest are lobulated nuclei, mesophilic granulocytes, early juvenile granulocytes and a few primitive granulocytes. Eosinophils and basophils were also increased. Hemoglobin and erythrocytes are mildly decreased, platelets are normal or increased in the early stages, and erythrocytes and platelets are decreased in the late stages. In terms of blood picture, it must be differentiated from leukemia-like reaction.
Bone marrow image: bone marrow is proliferative to extremely active, cell classification is similar to the peripheral blood, bone marrow film, can be seen in all stages of granulocytes, which is mainly in the middle and late juvenile granulocytes, progranulocytes and early juvenile granulocytes more than the normal increase, but generally not more than 5% ~ 10%, eosinophilic and/or basophilic granulocytes increase, erythrocyte lineage is relatively reduced, the granulocyte: red is about 10 ~ 50:1, juvenile erythrocytes and megakaryocytes often increase in early, late erythrocytes and platelets decrease. Megakaryocytes are often increased in the early stages and decreased in the late stages. 90% of the patients have a significant decrease in alkaline phosphatase activity of mature neutrophils.
Chromosomal examination: Ph' chromosome is seen in more than 90% of patients with lentigo, Ph' chromosome is considered to be a tumor marker of lentigo pluripotent stem cells, a few patients with lentigo are negative for Ph' chromosome, and according to the presence or absence of Ph' chromosome, lentigo can be classified as Ph' chromosome. According to the presence or absence of the Ph' chromosome, lentigo can be categorized as Ph' positive and Ph' negative, and the prognosis of the former is better than that of the latter.
Blood biochemistry: serum vitamin B12 concentration and vitamin B12 binding capacity is significantly increased as one of the characteristics of the disease, the magnitude of the increase is proportional to the degree of leukocytosis. The increase is due to a large number of normal and .
Typing and clinical manifestations of chronic myelogenocytic leukemia
Chronic leukemia is less common in pediatrics, accounting for about 3% to 5% of childhood leukemias, of which the main one is chronic myelogenors leukemia (CML).
The clinical manifestations of CML in infancy differ significantly from those of adult CML, so pediatric CML is generally classified into juvenile and adult types. In the literature, there are also four types: infantile, familial, toddler, and adult, of which the familial type is similar to the infantile type, except that it often develops in close relatives.
1. Juvenile chronic mydogenous leukemia (JCML) occurs almost exclusively in children under 5 years of age, especially in infants and children under 2 years of age. It is more common in males than in females. It may occur in children with familial neurofibromas, genitourinary malformations, or mental retardation.
The onset of the disease may be rapid or slow, and respiratory symptoms are often the main complaint. Most of them have maculopapular or eczema-like rashes on the face, or even suppurative rashes, and can also be seen in the skin café-au-lait spots, and the skin symptoms can appear months before the infiltration of leukemia cells. Lymph nodes are enlarged, even suppurative. Progressive hepatosplenomegaly. Bleeding secondary to thrombocytopenia is not uncommon.
JCML originates from pluripotent hematopoietic stem cells, which may cause dysplasia of the red lineage, abnormal platelet count and volume, and abnormal lymphocyte function. Unlike the adult type, its abnormal proliferation is mainly in the granulosa monocytic system, and in vitro stem cell culture mainly results in the formation of CFU-GM. Chromosomal examination is mostly normal, with isolated cases of -7, +8 (trisomy 8) or +21 (trisomy 21).
Peripheral blood picture was characterized by increased leukocytes, decreased platelets and moderate anemia. Leukocytes were moderately elevated, mostly below 100 x 109/L. Immature granulocytes and nucleated erythrocytes may be present in the peripheral blood with monocytosis. Leukocyte alkaline phosphatase is decreased and occasionally normal. Lysozyme is increased in serum and urine. hbF is increased. Bone marrow granulocyte:red is 3 to 5:1. granulocyte and monocyte lineages are hyperplastic and abnormal red lineage proliferation is seen. Primitive granulocytes are below 20%. Megakaryocytes were decreased. In vitro bone marrow cell culture was dominated by monocytes.
Because JCML is often associated with fever, hepatosplenomegaly, moderate anemia, and leukocytosis, it needs to be differentiated from infection-induced leukemia-like reactions. It should also be differentiated from infectious mononucleosis.
2. adultchronic myelogenous leukemia (ACML) onset of more than 5 years of age, 10 to 14 years of age is more common, rarely seen in children under 3 years of age. There is little difference between males and females. Due to the malignant proliferation of pluripotent hematopoietic stem cells, multiple lineages such as granulosa, erythropoietic and megakaryotic lineages are involved, and it can be transformed into lymphoblastic leukemia in the acute stage. The Ph1 chromosome (i.e., t(9:22)) is present in about 85% or more of affected children. For those who are negative for the Ph1 chromosome, they can be subdivided into two subtypes with bcr recombination (phbcr+CML) and without bcr recombination (PH-bcr-cml) using molecular biology techniques. The clinical symptoms of the former are similar to those of PH1 chromosome-positive individuals, while those of the latter are atypical.
The onset of the disease is slow and begins with mild symptoms of malaise, weight loss, and bone and joint pain. Signs are seen as giant spleen, hepatomegaly, mildly enlarged lymph nodes, and optic nerve papillary edema. Rarely there are bleeding symptoms.
Peripheral blood picture is mainly leukocytosis, 80% above 100×109/L. Hematocrit was around 80 g/L. Thrombocytosis. Classification of visible granulocytosis, including acidophilic and basophilic granulocytosis. Primitive granulocytosis is not evident, with predominance of intermediate, late juvenile and mature granulocytes. Leukocyte alkaline phosphatase is decreased. hbF is not increased. Serum immunoglobulins are not increased. Bone marrow hyperplasia is active, with predominantly granulomatous hyperplasia, with <10% primitive granulocytes, mostly medium and late juvenile granulocytes and rod-shaped nucleated cells. The granulocyte:red ratio was 10-50:1, and myelofibrosis was seen in some patients. Bone marrow megakaryocytes were markedly increased, with mature megakaryocytes predominating. Serum and urinary lysozyme are not increased, but VitB12 and VitB12 transport protein are increased. Bone marrow culture colonies and clusters were increased.
Clinical manifestations of chronic lymphocytic leukemia
Typical B-cell chronic lymphocytic leukemia has a slow onset and is often asymptomatic in the early stages, and may be detected incidentally on physical examination or routine blood tests, while others are detected by enlarged lymph nodes or liver and spleen.
(A) lymph node enlargement is the most common (accounting for 70%), can be generalized, mild to moderate enlargement, occasionally obviously enlarged, no pressure pain, touch a rubbery feeling, and the skin is not adherent to the neck, axilla and groin and other places. Tonsils, lacrimal glands, salivary glands when involved, can produce Mikulicz syndrome.
(ii) Hepatosplenomegaly Splenomegaly is common (40%), mild to moderate enlargement, up to the pelvis in advanced stages, and occasionally splenic infarction or splenic rupture may occur. Hepatomegaly (10%) is not as great as that of the spleen, and when marked enlargement is accompanied by hepatic impairment, it often suggests an advanced case.
(3) other organs infiltration manifestation 50% of the patients have skin manifestations, more common than slow-growing, specific such as nodules, erythroderma, etc., but also non-specific such as pruritus. Gastric and small intestinal infiltration is common, which can be seen as hyponatremia, abdominal distension, dyspepsia, black feces, diarrhea and so on. Pulmonary infiltrates are mainly diffuse nodules, cornified infiltrates (40%) and pleural effusion (15%). Pleural fluid is often hemorrhagic, and celiac pleural fluid can also occur due to lymphatic obstruction. Skeletal lesions commonly include decalcification and osteopenia (5%), and osteolysis is rare. On pathologic examination more than 60% of patients have bilateral leukemic infiltration of the kidneys, but the lesions are usually mild, and about 20% of patients have proteinuria and microscopic hematuria. Neurologic lesions include patchy cerebral infiltration and even nodular brain tumor formation, but also meningeal, 7th pair of cranial nerves, hypothalamus, pituitary and peripheral neuropathy, and intracranial pressure may be increased.
(IV) Immunodeficiency manifestations Higher incidence of herpes zoster or herpes simplex. Patients are prone to septic infections such as pneumonia. It is also associated with second malignant tumors, especially skin and colon tumors. Diffuse histiocytic lymphoma, known as Richter's syndrome, occurs in about 3.3% of patients. Rheumatoid arthritis and myasthenia gravis can also occur.
T-cell chronic lymphoma is characterized by rapid onset, hepatosplenomegaly, moderate lymphocytosis, frequent invasion of the central nervous system, gonads, and deep dermis, poor response to treatment, and short survival time.
Diagnostic criteria for sexual lymphoblastic leukemia
(I), history and symptoms
(1) History questions: slow onset, the patient is mostly asymptomatic, the consultation should pay attention to whether there is a low-grade fever, night sweats, easy to infect the performance.
(2) Clinical symptoms: fatigue, lethargy, poor appetite, night sweats, loss of energy, fever, and occasional itching of the skin.
(2) Physical examination findings
Enlarged lymph nodes all over the body, moderately hard, mobile, and fused with each other in the late stage; mild enlargement of the liver and spleen, and obvious enlargement of the spleen in the late stage. Bone pain was not obvious. Bleeding spots were visible on the skin in the advanced stage.
(C), auxiliary examination
1. Blood picture: positive cell positive pigment anemia. White blood cell count >10×109/L, classification: lymphocytes >50%, absolute value >5.0×109/L; mainly mature lymphocytes, naive lymphocytes and heterogeneous lymphocytes can be seen. Platelets were normal or decreased.
2. Bone marrow image: active to extremely active proliferation, with mature lymphocyte hyperplasia obvious, accounting for more than 40%, primary and naive lymphocytes <10%. The red lineage and granulocyte lineage are relatively reduced, and the megakaryocytes are normal or reduced.
3. Blood immunoglobulin decreased; or for single immunoglobulin increased, mostly IgM type. κ light chain or λ light chain test positive.
(4) Clinical staging and differential diagnosis of CLL
1. Staging: Stage I: lymphocytosis, which may be accompanied by enlarged lymph nodes.
Stage II: stage I + hepatomegaly or splenomegaly.
Stage III: Stage I or II + anemia (hemoglobin <100g/L) or/and thrombocytopenia (<100×109/L).
2. Differential diagnosis should be differentiated from tuberculous lymphadenitis, lymphoma, infectious mononucleosis, hairy cell leukemia, and young lymphocytic leukemia.
Leukemia treatment
I. Chemotherapy
In June 1946, the first case of leukemia treated with chemotherapeutic drugs in foreign countries to obtain remission, opened a new era of leukemia treatment. 70 years after the combination of chemotherapy, maintenance, consolidation of treatment and other strategies have been gradually perfected, and in recent years, with the application of new anti-leukemia drugs, the efficacy of the treatment of leukemia has been a great progress, and the latest The latest research results show that the complete remission (CR) rate of childhood ALL has reached 85%-95%, and the 5-year disease-free survival is ≥50%-70%. The CR rate of adult ALL is close to 75%-85%. 5-year disease-free survival ≥40%-50%, and the CR rate of adult acute myeloid leukemia is 65%-85%. long-term disease-free survival under 60 years old can reach 40%-50%. With the progress of leukemia treatment research, the efficacy is still improving. It offers hope for the eradication of leukemia. In order to achieve this goal, it is necessary to integrate modern treatment means according to the different characteristics of each patient, fully aware of the treatment of leukemia as a whole, especially to analyze and recognize each case of the patient's own characteristics, such as age, gender, type of leukemia, hematological characteristics, cytogenetic and molecular biological characteristics, and the cellular dynamics of leukemia cells. On this basis, we design the best treatment plan for the patient, and reasonably use modern treatment means, such as chemotherapy, hematopoietic stem cell transplantation, biological and gene therapy, and combination of traditional Chinese and Western medicines to cooperate and coordinate with each other, so as to avoid all kinds of toxic side effects to the greatest extent possible. It can kill leukemia cells and make patients achieve the purpose of long-term survival and even cure.
Chemotherapy is generally divided into induction remission therapy (chemotherapy for the initial treatment of leukemia to achieve CR); consolidation therapy (chemotherapy similar to the induction regimen after CR); maintenance therapy (refers to the use of chemotherapy that is weaker than the intensity of the induction chemotherapy and less myelosuppressive); intensive therapy (refers to chemotherapy that is stronger than the induction regimen) is divided into early intensive and late intensive.
The important principles of chemotherapy are early, adequate dose, combination, and individualized treatment. Increased dose and intensity of chemotherapy is one of the main factors in increasing CR rates and long-term survival in leukemia patients. When leukemia patients CR when bone marrow morphology classification leukemia cells although <5%, but the total number of leukemia cells in the body can still be as high as 106-9, if not as early as possible for early reinforcement after CR, leukemia cells will soon proliferate, growth, leading to relapse and drug resistance, so leukemia patients should be as early as possible for a sufficient amount of effective post-CR treatment.
Since the 80's, chemotherapy for leukemia has mostly adopted combination chemotherapy, which focuses on the cell cycle and sequential use of drugs, and generally selects a variety of drugs that act on different cell cycles and can promote each other and strengthen the ability to kill leukemia cells, but with different toxicity and payment effects, or can alleviate each other's toxicity and side effects and relatively selective leukemia cell killing combination chemotherapy.
The principle of individualization of leukemia chemotherapy is the development of the need for leukemia treatment research, its principles emphasize four aspects ① for different types of leukemia should be selected for different chemotherapy regimens, and ALL should be selected and AML different drugs, dosage, duration of treatment. ② For leukemia individuals with different prognostic factors, their treatment regimens should be focused and different, such as for T-ALL and B-ALL, in addition to the conventional regimen, the addition of CTX or MTX and Ara-C can significantly improve their CR rate and survival. (iii) The health status of patients before chemotherapy is also an issue to be considered for individualization of chemotherapy. The amount of chemotherapeutic drugs should be reduced for patients with liver, kidney and heart insufficiency. ④Closely observe the patient's blood and bone marrow changes during chemotherapy, and increase or decrease the dose of chemotherapy in a timely manner to differentiate between different situations.
The reason of leukemia chemotherapy failure: chemotherapy failure is mainly due to infection and bleeding caused by early death during the chemotherapy period, or leukemia cells resistant to the drug without effect. The general failure of the following cases: ① leukemia cells are completely resistant to drugs, manifested in the inhibition of bone marrow proliferation after chemotherapy, but leukemia cells do not reduce; ② leukemia cells are partially resistant to drugs, manifested in the partial reduction of leukemia cells after chemotherapy, but it is not ideal, and then leukemia cells and then proliferate; ③ myeloid dysplasia, the bone marrow hematopoiesis did not recover in the four weeks after the chemotherapy; ④ poor myeloid dysplasia and death in four weeks; ⑤ chemotherapy because of Bleeding, infection and other uncontrollable early death; (6) CR after chemotherapy but extramedullary leukemia exists. There are still a few patients, after chemotherapy, leukemia cells decreased rapidly, bone marrow, blood also rapid suppression, but soon leukemia cells and WBC again rapid multiplication, rapid deterioration of the condition, such patients are difficult to deal with, poor prognosis, lack of effective treatment.
Second, the combination of Chinese and Western medicine
Combination of Chinese and Western medicine can make up for the shortcomings of Western chemotherapy, and solve the problem of resistance to chemotherapeutic drugs. At the same time, some hypoproliferative leukemias, which have low WBC and platelet counts, can not withstand the powerful chemotherapeutic drugs, and can be treated with Chinese medicine, which can avoid the toxic side effects of Western drugs and relieve the condition. It can alleviate the condition, and the combination of Chinese and Western medicine has the following forms of treatment.
1. Simple Chinese medicine treatment, applicable to low proliferative leukemia, can not tolerate chemotherapy, available Chinese medicine. Then the beginning of the disease has never used chemotherapy drugs, has not yet produced drug resistance, available Chinese medicine, Chinese medicine treatment is suitable for naive cells are not very high patients. Adhere to the daily medication, after a period of time (usually in 3-4 months) can achieve CR. our hospital treatment of this disease, put forward the "cell reversal method" new method of treatment of leukemia, "cell reversal" is similar to the induction of differentiation in Western medicine. Its content is to dispel blood stasis, clear blood, support the right, detoxification of a series of drug combinations, effectively control the growth of leukemia cells, and gradually make it transformed and decomposed, while killing some leukemia cells, and then through the regulation of human immunity, improve human metabolism, so that the toxins are discharged from the body. Through the overall regulation of the human body and targeted, comprehensive effect as above, the purpose of curing leukemia is achieved. Traditional Chinese medicine has brought us a ray of hope in the treatment of leukemia. We will conduct more in-depth research in this area to find a safer and more effective way to treat leukemia.
2. Combination of Chinese and Western medicines, i.e., after the chemotherapy period with supporting Chinese medicine. In order to raise white blood cells, platelets, enhance the body's immune function and anti-infection. Stop bleeding function, in the chemotherapy remission period can still use Chinese medicine, one is to promote the body's recovery, the second is to consolidate the effect of chemotherapy, delay the next chemotherapy time.
Three, biological regulator therapy
With the development of immunology and gene technology biological regulator therapy has been used in the clinic, in which interleukin II, a variety of hematopoietic stimulating factors such as GM-CSF, G-CSF, M-GCSF erythropoietin, swelling and pain necrosis factor, interferon, etc., clinically verified, interleukin Ⅱ, LAK cells, etc., on the leukemia has a certain efficacy G-CSF, GM-CSF, etc. are used in patients with myelosuppression after chemotherapy, which can significantly shorten the suppression of bone marrow and blood, accelerate the remission and reduce the occurrence of complications.
Four, gene therapy
Gene therapy is the introduction of exogenous genes to the target cells (tissues), in order to correct the compensation or inhibit certain abnormal or defective genes, so as to achieve the therapeutic purpose. Its treatment can be divided into four categories: ① gene compensation: the normal function of the gene into the target cell to compensate for the lack of or inactivation. ②Gene Correction: Eliminate the abnormal genes of the original drug and replace them with exogenous genes. ③Gene compensation: the expression level of exogenous normal genes exceeds the expression level of abnormal genes of the original drug. ④ Antisense technology: Suppression or closure of abnormal or missing gene expression by synthetic or organism-synthesized specific complementary DNA or RNA fragments or their chemical modification products.
Gene therapy for leukemia as a new method is gradually transitioning from theoretical research to clinical trials, and has passed the phase II clinical trial stage in the U.S. Currently, gene therapy is mainly the application of antisense oligonucleotides to close the proto-oncogenes. Antisense technology can treat the target basic and its products without changing the gene structure. CML is currently the most studied leukemia by antisense nucleic acid technology, through the improvement of the existing technology, the use of transporter-killed viruses to direct a variety of antisense DNA/RNA and auxiliary gene systems including BCR/ABL fusion genes, it is expected that a breakthrough in gene therapy for CML will be achieved soon.
V. Bone Marrow Transplantation (BMT)
1. Allogeneic Bone Marrow Transplantation (Allo-BMT) is a therapeutic method of implanting hematopoietic stem cells from healthy bone marrow into a patient to rebuild the hematopoietic and immune functions of the patient after the patient has been pretreated with mega-dose radiotherapy and chemotherapy.
The use of bone marrow in the treatment of disease began in 1891 Brown-Sequard gave patients oral bone marrow treatment of anemia, Osgood in 1939 for the first time intravenous infusion of bone marrow, in 1951 Lorenz and other first successful bone marrow transplantation test, the 1970s to the development of HLA tissue matching technology, transplantation of immunology and other basic medical research, make the clinical application of BMT. In the 1970s, the development of HLA tissue matching technology, transplantation immunology and other basic medical research in-depth, so that the clinical application of BMT has developed rapidly, and a number of BTM centers have been established around the world. China's BMT has also made great progress, and in recent years the number of allogeneic BMT cases in China has reached more than 300, and the therapeutic effect has basically reached the international equivalent level.
The long-term disease-free survival rate of Allo-BMT for leukemia reaches about 50%. According to the 1993 International BMT Registry statistics, the five-year survival rate of BMT treatment of leukemia is: acute lymphoma (ALL) first complete remission (CR1) is about 50%, ALL second complete remission (CR2) or more than the second complete remission is about 32, ALL recurrence of its is about 18%, acute myeloid leukemia (AML) CR1 is about 52%. CR2 or >CR2 is about 35%, chronic myeloid leukemia (CML) chronic phase is about 45%, accelerated phase is about 36%, acute phase is about 6%, it can be seen that leukemia patients with chemotherapy CR should be early BMT treatment.
Where the risk of BMT treatment is, there are two main points: one is that there are many transplantation-related complications in BMT, and the other is that there is still the problem of leukemia relapse after BMT: the main transplantation-related complications are: hepatic veno-occlusive disease, which has a morbidity rate of 25% and a mortality rate of 80%, and graft-versus-host disease, which has a morbidity rate of 10-80%.The rate of leukemia relapse after BMT is about 15- 30%.
Steps of Allo-BMT:
1) Selection of HLA (human leukocyte antigen) fully compatible donors, in the order of sibling sibling HLA genotypic compatibility, followed by family members with HLA phenotypic compatibility, and then a family member with HLA locus incompatibility or an unrelated donor with HLA phenotypic compatibility, and finally an HLA locus incompatible unrelated donor or a family member with two or three incompatible HLA loci.
2) Preparation of the recipient, should verify and determine the diagnosis and typing of leukemia, the general age should be limited to less than 45-50 years old, the function of the important organs is basically normal, to clear the body of multiple foci of infection, a comprehensive experience and necessary laboratory tests, auxiliary tests are generally more than a dozen. Recipients are admitted to the sterile laminar flow ward one week in advance.
3) for histocompatibility antigen and gene matching.
4) BMT pretreatment should be up to three months, one is to destroy the original hematopoietic cells in the recipient's body, to prepare the implanted hematopoietic stem cells implantation of growth space. The second is to inhibit the immune cells and functions in the recipient's body, which is conducive to the implantation of bone marrow. Third, it removes and kills a large number of leukemia cells in the recipient's body.
5) Collection, processing and infusion of bone marrow: on the day of bone marrow infusion, the donor's bone marrow is collected in the operating room under aseptic conditions, filtered and then infused intravenously into the recipient as soon as possible to avoid the loss of hematopoietic stem cells. The bone marrow of those with ABO blood group incompatibility should be processed before transfusion.
6) Nutritional and supportive therapy often necessary during BMT.
7) Early prevention and treatment of BMT complications, exclusion of GI toxicity, 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 hematopoietic reconstruction and implantation of BMT, after BMT, patients have to go through the process of failure of the original hematopoietic system and hematopoietic reconstruction of the newly implanted bone marrow, and the gradual increase of reticulocytes after BMT is regarded as an early indicator of bone marrow implantation. Normalization of peripheral blood picture usually takes 3-6 months. In addition, cytogenetic analysis of erythrocyte antigen and leukocyte antigen tests can directly demonstrate the success of BMT implantation.
10) The recurrence of leukemia after BMT, generally speaking, the recurrence rate is high in the older age group, the recurrence rate is high in the non-first complete remission and non-chronic phase of CML, and the recurrence rate is high in the low dose of TBI (total body irradiation) in the pretreatment of BMT, and most of the recurrence is the recipient type recurrence (95%). The reasons for relapse were mainly related to the incomplete removal of leukemia cells during BMT, i.e., more residual leukemia cells in the body and the weak anti-leukemia effect of the grafts after BMT.
2. Autologous stem cell transplantation and umbilical 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, so that they will be protected from the damage caused by high-dose radiotherapy, and then infused back into the high-dose radiotherapy after the high-dose radiotherapy, and the autologous hematopoietic stem cells can be derived from the bone marrow, and also can be collected from the patient's peripheral blood. Autologous stem cell transplantation can be used in older patients because there are no comorbidities such as graft-versus-host disease. The procedure involves collecting the hematopoietic stem cells, storing them at temperatures above and below zero, and then thawing them for re-infusion, which requires purification of the autologous stem cells and decontamination of residual leukocytes prior to transplantation. Necessary examination and pretreatment of radiotherapy are carried out for patients, and supportive treatment such as controlling infection and bleeding should be given after transplantation. The effect of autologous stem cell transplantation is better than that of conventional chemotherapy, and it has been reported to be one of the effective consolidation therapeutic measures after CR of acute leukemia, and the disadvantage is the high rate of recurrence, and there is no uniform statement on the time of its survival and its cause.
Treatment of chronic lymphocytic leukemia
Benign type (stage A) lymphocytes are mildly increased, the condition is stable, generally do not need chemotherapy, to regular observation, symptomatic treatment. For the progressive type (stage B to C), patients with obvious symptoms and progressive enlargement of lymph nodes and spleen should be treated with aggressive chemotherapy.
(I) Chemotherapy
1. Single chemotherapy ①Azelaic acid phenylbutyrate is the first choice of drugs, the best effect, remission rate of 50-98%, the general dose of adults is 0.08-0.1mg/kg-d, should be discontinued when the blood image is lower than normal values. For maintenance therapy, the dose should be adjusted to 0.04-0.08mg/(kg-d) until remission. Literature also advocates the application of intermittent high-dose phenylbutyrate nitrogen mustard 0.4 to 0.8mg/(kg-d) for 4 days, with an interval of 4 to 6 weeks, as an induction of remission, which may be preferable to a smaller dose, but should be wary of myelotoxic reactions. ② Cyclophosphamide has similar efficacy to nitrogen mustard phenylbutyrate, and is commonly used in those who are insensitive to nitrogen mustard phenylpropionate, have more severe disease, more young lymphocytes or thrombocytopenia. Commonly used dose 1 ~ 3mg / (kg - d), oral or 20mg / kg, static injection, every 2 ~ 3 weeks. ③ Fludarabine monophosphate, the mechanism of action is related to the interference with adenosine nucleoside acid metabolism, half effective in progressive slow gonorrhea, can be 25-30mg/(m2-d), 5 days, IV, repeat the course of treatment every interval of 4 weeks. ④ 2-chlorooxyadenosine (2-chlorooxyadenosine), according to 0.05～0.2mg/kg-d×7, continuous IV, the efficiency is 55%. ⑤ Deoxycoformycin (Deoxycoformycin) is effective in 25% of patients, for B-slow gonorrhea, 4mg/m2 weekly or every 2 weeks by IV; for persistent T-slow gonorrhea can be 5-19mg/(m2-d) for 3-5 days by IV.
Complicated autoimmune hemolytic anemia or thrombocytopenic purpura and resistance to alkylating agents for the indication of the application of prednisone, can specifically lyses the slow lymphocytes, the common dose of 20 to 60mg/d, after the effect of the available intermittent maintenance, 2 days a week to serve, 40 to 60mg/d, generally do not advocate long-term application. There are also advocated the application of short-course (5 days) prednisone higher dosage (80mg/d) program, as a combination therapy with phenylbutyrate nitrogen mustard.
2. Combined chemotherapy can be tried with multiple myeloma M2 regimen, complete remission of 15%. liepmen (1978) and other application of anti-lymphoma cop treatment of 36 cases of chronic lymphoma, complete remission of 16 cases, the median survival of more than 2 years; CHOP regimen for the treatment of stage C patients with chronic lymphoma, the effectiveness of the rate can also be up to 50 to 70%, the dosage method, see the relevant diseases.
(II) Radiation therapy There are obvious lymph node enlargement (including mediastinum or giant spleen) can be considered to use local irradiation to relieve the symptoms of compression.Sparr et al. (1974) applied thymus irradiation treatment for 22 cases, complete remission in 11 cases, and partially remission in 7 cases.Heilmann (1978) applied extracorporeal blood cell irradiation treatment for 12 cases, see the number of B lymphocytes decreased significantly, while the T lymphocytes did not change. and no change in T-lymphocytes, but special equipment was needed. Radioactive 32P is only considered for those who are ineffective in chemotherapy, and the dose should be smaller than other types of leukemia, 1 to 2 mci (3.7×107-7.4×107Bq) each time, 1 to 2 times a week.
(3) Other treatments Those with hypogammaglobulinemia and recurrent infections can be given regular static injections of gammaglobulin. Splenectomy may be considered when treatment with adrenal glucocorticoids or radiation to the splenic region is ineffective. The use of lymphocyte separation may also be helpful in those with markedly increased lymphocyte accumulation.
Treatment of Acute Lymphoblastic Leukemia
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The prognosis for ALL has improved markedly over the past 20 years, thanks to the advent of new antileukemic drugs and the improvement of new chemotherapy regimens and treatments. Modern treatment is no longer about simply obtaining remission, but about striving for long-term survival and ultimately a cure and a high quality of life.
1. Combination chemotherapy is the core of leukemia treatment and is carried out throughout the treatment. Its purpose is to kill leukemia cells as much as possible, remove the trace residual leukemia cells in the body, prevent the formation of drug resistance, restore the hematopoietic function of the bone marrow, achieve complete remission as soon as possible, and damage as little as possible to normal tissues to reduce the sequelae of the treatment in the late stage.
Leukemia remission criteria are:
(1) complete remission (CR) ① clinical anemia, bleeding, infection and leukemia cell infiltration manifestations; ② blood hemoglobin > 90g / L, leukocytes are normal or reduced, classified without na?ve cells, platelets > 100 × 109 / L; ③ bone marrow image of the primitive cells plus the early juvenile stage of the cell (or na?ve cells) <5%. The erythrocyte system and megakaryocyte system are normal.
(2) Partial remission 1 or 2 of the 3 clinical, blood and bone marrow images do not meet the criteria for complete remission, and the bone marrow image of primitive cells plus early stage cells <20%.
(3) Failure to achieve complete remission in 1 or 2 of the 3 clinical, hematologic, and bone marrow categories, and >20% of the primitive cells plus early juvenile cells in the bone marrow image, including invalid patients.
Commonly used antileukemic chemotherapeutic drugs For a detailed description of the drugs, see the Oncology section for an overview. For the use, dosage, indications, and side effects of these drugs in the treatment of leukemia, refer to the Oncology Chapter for a brief list of commonly used anticancer drugs (Table 33-2).
When designing a chemotherapy regimen, the combination of cycle-specific and cycle-nonspecific drugs should be considered, and cycle-specific drugs should be selected with drugs of different phases.