1. How to understand the function of bone marrow and bone marrow ............................................... top
> > > > Blood is a red, opaque and viscous liquid composed of plasma (the liquid part of blood) and blood cells (erythrocytes, granulocytes, lymphocytes, monocytes, platelets, etc.). The total blood volume of a normal person is about 8% of the body weight. Blood is constantly flowing in blood vessels, which are "rivers" that transport nutrients, carry metabolites, regulate internal environment balance and exercise defense functions. People's understanding of blood is also gradually deepening. The ancient Egyptians advocated bathing blood to restore health. Before 1900 discovered ABO blood group of red blood cells, many people suffered from severe hemolysis and even died because of blood group incompatible transfusion. Bone marrow puncture needle was invented in 1929, and bone marrow cells became an important part of blood research.
> > > > Normal people's blood cells maintain a relatively constant number and function. This constant is the dynamic balance of metabolism, that is, aging and dead cells are often replaced by new cells. For example, the average life span of human red blood cells is about 120 days, and the life span of platelets is about 7- 10 days. A normal adult has about 10 red blood cells aging and dying every day, and a similar number of red blood cells are regenerated.
Adult hematopoietic organs are mainly limited to bone marrow, spleen and lymph nodes. However, the main function of spleen and systemic lymph nodes after birth is to promote the secondary proliferation of lymphocytes, that is, the immune response of lymphocytes to reproduce after contact with antigens. Therefore, the hematopoietic function of bone marrow is particularly important. After birth, bone marrow is the only place to produce red blood cells, granulocytes and platelets under normal circumstances, and bone marrow also produces lymphocytes and monocytes.
> > > > Bone marrow is a spongy tissue, which exists in the bone marrow cavity of long bones (humerus and femur) and the grid between cancellous bones of flat bones (such as ilium). The bone marrow that can produce blood cells is reddish and is called red bone marrow. As soon as a person is born, red bone marrow fills the whole bone marrow cavity. With the increase of age, fat cells increase, and a considerable part of red blood cell bone marrow is gradually replaced by yellow bone marrow. Finally, almost only the flat bone marrow cavity has red bone marrow. This change may be due to the fact that adults do not need all bone marrow cavity hematopoiesis, and some bone marrow cavity hematopoiesis is enough to supplement the needed blood cells. When the body is seriously ischemic, part of yellow bone marrow can be replaced by red bone marrow, and the hematopoietic capacity of bone marrow is significantly improved.
& gt& gt& gt& gt In the past thirty years, the research on hematopoiesis has developed rapidly. It has been proved that there are hematopoietic stem cells in human bone marrow, and their number is less than 1% of the total number of bone marrow cells. They have high self-renewal ability and can differentiate into progenitor cells of various blood cell systems (such as lymphoid stem cells and granulocyte stem cells), and then differentiate and proliferate into various primitive and mature blood cells. Finally, these mature blood cells enter the blood through the bone marrow and play their respective physiological roles. Human hematopoietic stem cells have different functions because of their different locations. Part of it exists in the stem cell pool, which is a reservoir for human hematopoietic cells to adapt to and meet the hematopoietic needs of various States; The other part exists in the proliferation pool, and these cells are constantly proliferating and updating to make up for the lack of blood cells caused by cell aging or loss and maintain the blood flow balance of the human body.
& gt& gt& gt& gt The hematopoietic function of bone marrow is extremely strong, and the highest hematopoietic capacity of bone marrow can reach 9 times that of normal hematopoiesis. If only110 bone marrow is preserved, normal hematopoietic function can be completed, so a small number of bone marrow donors have no effect on the body. The hematopoietic tissue of human body has a strong compensatory function. After extracting part of bone marrow, hematopoietic stem cells will proliferate rapidly and completely return to the original level within a week or two. Therefore, donors will not only affect their hematopoietic function, but also exercise their hematopoietic system and be more energetic.
2. Leukemia and bone marrow transplantation at the top of ................................................................................
& gt& gt& gt& gt Bone marrow transplantation refers to a therapeutic method of transplanting other people's bone marrow into patients to make them grow and reproduce, rebuild immunity and hematopoiesis. Bone marrow transplantation is divided into autologous bone marrow transplantation and allogeneic bone marrow transplantation, and allogeneic bone marrow transplantation is divided into consanguineous bone marrow transplantation (siblings) and unrelated bone marrow transplantation (volunteers). Autologous bone marrow transplantation is easy to relapse and is rarely used in clinic. At present, allogeneic bone marrow is the first choice for bone marrow transplantation.
& gt& gt& gt& gt bone marrow transplantation is a breakthrough in the treatment of leukemia in recent years. Leukemia patients produce abnormal white blood cells due to malignant transformation of hematopoietic tissue, which inhibits the function of normal blood cells. Traditional treatment only uses chemotherapy to destroy leukemia cells, and most patients' leukemia will recur. Almost all patients with chronic myeloid leukemia will have a mutation, and too much chemotherapy and radiotherapy will make the normal hematopoietic cells of patients unable to recover. In the treatment scheme of bone marrow transplantation, patients need to receive large doses of chemotherapy and whole body radiotherapy, and the diseased hematopoietic stem cells in bone marrow are destroyed, while the transplanted normal bone marrow completely replaces the original diseased bone marrow of patients, rebuilds hematopoietic and immune functions, and has achieved good results in clinic, greatly improving the cure rate of leukemia. Brought the patient a second life.
> > > > Bone marrow transplantation has become the only treatment for many diseases. Besides leukemia, it can also treat aplastic anemia, thalassemia, myelodysprosia, hereditary red blood cell abnormality, plasma cell abnormality and other hematological diseases, as well as various intractable diseases such as malignant tumor of lymphatic system, hereditary immunodeficiency and severe radiation sickness.
3. Bone marrow transplantation and hematopoietic stem cell transplantation at the top of .........................................................................
& gt& gt& gt& gt The principle of hematopoietic stem cell transplantation is exactly the same as that of bone marrow transplantation, but the collection method of hematopoietic stem cells is different. Hematopoietic stem cells mostly exist in bone marrow. Bone marrow transplantation needs to extract bone marrow from bone marrow cavity through bone marrow puncture, and then collect hematopoietic stem cells and input them into patients. Stem cell transplantation is to release hematopoietic stem cells from bone marrow into blood and collect hematopoietic cells from peripheral blood through a blood cell separator. In order to carry out bone marrow transplantation, voluntary donors need to perform local anesthesia and drill holes in the bone several times to extract hundreds of milliliters of bone marrow mixture; Stem cell transplantation only needs to collect blood from volunteers' veins and enrich it with machines, and only needs 50 ml of stem cells. Due to the balance of the total amount of import and export, donors will not have disorder of circulatory system after collection, which is very safe for human body. At present, the donor transplantation provided by China (Shanghai) Bone Marrow Bank adopts hematopoietic stem cell transplantation. In order to avoid confusion, the names of bone marrow transplantation, bone marrow donor and bone marrow bank are still used.
4.HLA matching and bone marrow transplantation at the top of ...............................................................................
One of the keys to successful bone marrow transplantation is HLA (human leukocyte antigen) matching. If the HLA of bone marrow donor is different from that of patient (recipient), serious rejection will occur and even endanger the life of patient. HLA typing is much more complicated than ABO blood group. Everyone gets a series of genes (HLA haplotypes) from their parents instead of one gene. Everyone has inherited two strings of candied haws, and the "red fruit" (genes) on candied haws are A, B, C, D, DR, DQ and DP in turn. For example, A has 28 kinds of "red fruits" (labeled as A 1, A2, A3, A9 ...), B has 6 1 kind (labeled as B5, B7, B8, B 12 ...), and DR has 24 kinds (labeled as DR). Colorful red fruits have a number of 164, such as random combinations of red fruits with different genetic arrangements. According to theoretical calculation, "sugar gourd" has more than 500 million changes, which can combine with more than 3.3 billion HLA typing. Theoretically, the number of HLA typing is huge, but it is not the case for a specific nation. For example, some yellow people don't have HLA antigens in whites and blacks, and China people don't have HLA antigens unique to whites and blacks. At the same time, HLA genes are not randomly matched, but have certain rules. Because of the above reasons, the actual number of HLA typing is greatly reduced.
The classification of>& gt& gt& gtHLA is common, rare and rare. Common HLA typing can be found in 300-500 people, while rare HLA typing may be one in ten thousand, and rare HLA typing will be found in tens of thousands or even hundreds of thousands of people. The HLA typing of different races is very different, and all countries in the world have established their own bone marrow bank (HLA data retrieval center for bone marrow donors) to meet the needs of their own patients. At present, the largest bone marrow bank in the world is in the United States, with 4.6 million voluntary donors, and the retrieval success rate is 80%. The average number of cases of donating bone marrow for transplantation every month is 108. At present, the largest Chinese bone marrow bank is the Tzu Chi bone marrow donor Search Center in Taiwan Province Province, with a total of 230,000 registered donors. The bone marrow of whites and blacks is not suitable for China people. The establishment of a Chinese bone marrow bank totally belonging to China people can not only help China citizens, but also serve Chinese people all over the world.
5. The process of bone marrow transplantation at the top of ..................................................................................
& gt& gt& gt& gt Before conventional bone marrow transplantation, only HLA-A, B and DR should be the same. Because the diversity of HLA-AB is the most obvious, the general volunteers are classified according to HLA-AB. After retrieval, the donor and recipient matched by HLA-AB, and then the donor detected whether they matched by HLA-DR. If the donor and recipient HLA are completely matched and the donor health examination is qualified, the transplant operation can be prepared. First, the cancer cells in the patient's body are destroyed by chemical drugs and radiotherapy, which also kills the normal hematopoiesis of the patient, reduces the immunity of the human body, and is prone to infection. It must be transplanted in a sterile ward (laminar flow room). Transplantation is like blood transfusion. The implanted hematopoietic stem cells propagate in the patient's body, rebuild the hematopoietic and immune systems, and the patient gradually recovers. The effective cure rate of bone marrow transplantation for leukemia can reach 75-80%.
In the process of transplantation,>& gt& gt& gt will have different degrees of rejection. Because the immune system can distinguish foreign bodies? Quot dissidents ",and attack it, push it out, this process is called" exclusion ". If the donor and the recipient are related by blood, the rejection will be weaker; If it doesn't matter, the reaction will be heavier. Another rejection reaction is graft-versus-host reaction (GVHD), that is, the immune cells in the donor tissue act on the recipient (host), and the host tissue antigen is also foreign to the donor immune cells. The growing donor immune cells "attack" the recipients more and more, resulting in "graft-versus-host reaction". Symptoms of GVHD include: fever, hepatitis, severe diarrhea, bone marrow suppression and infection, and severe cases can be complicated with fatal reactions. The incidence of GVHD was 1-5% in twins, 36% in relatives and 50-70% in unrelated relationships. However, although GVHD is a threat to patients, it has anti-leukemia effect and can reduce the recurrence of leukemia after transplantation. Appropriate immunosuppressive measures can be taken in the treatment to save patients' lives.
6. Conditions for donating bone marrow .................................................................................. Top
The ideal donor for>& gt& gt& gt bone marrow transplantation is identical twins, because their genetic material is exactly the same. The bone marrow transplantation between them is very effective and there are few rejection reactions, but there are few twins after all. Children's HLA typing comes from their parents. For example, if the father is A and B and the mother is C and D, then the child may have four types: AC, AD, BC and BD. What is the HLA matching rate between brothers and sisters? 5%, so it is easier for patients to find donors from their compatriots. However, the family scope is shrinking, and most patients still need unrelated bone marrow donor people.
& gt& gt& gt& gt The suitable age for donating bone marrow is 18-45 years old, and the health requirements are the same as those for donating blood, that is, the donor's health cannot be affected by donating bone marrow, and new unfavorable factors cannot be added to patients by accepting bone marrow. It is important that blood donors be free from blood infectious diseases, such as hepatitis B and hepatitis C.
I. Overview of Bone Marrow Transplantation
The essence of bone marrow transplantation (BMT) is hematopoietic stem cell transplantation, and stem cells have the ability to replicate and differentiate into hematopoietic and immunocompetent cells. According to the different sources of stem cells, they can be divided into autologous, allogeneic and allogeneic BMT. Homologous bone marrow transplantation refers to transplantation between identical twins. Because the donor and recipient genes are the same, there is no immune incompatibility like autologous bone marrow transplantation. Allogeneic BMT donor cells are genetically different from recipient cells. Compared with organ transplantation such as kidney, liver and heart, allogeneic BMT is more prone to rejection. Once donor bone marrow is transplanted, graft versus host disease (GVHD) may occur. Therefore, strict donor-recipient tissue matching is needed, and the recipient must be pretreated with immunosuppressant before transplantation.
Second, the indications of bone marrow transplantation
Allo-BMT can correct serious irreversible diseases of hematopoietic system and immune system of recipients, and has been applied to the following diseases with satisfactory results.
1. hereditary diseases
(1) Immunodeficiency: X-linked EBV lymphoproliferative diseases of severe combined immunodeficiency disease (SCID) and Wiskott-Aldrich syndrome.
(2) Congenital anemia: thalassemia gravis, sickle cell anemia and Fanconi anemia.
(3) Metabolic disorders: mucopolysaccharide storage disease and lipodystrophy.
2. Primary or acquired severe aplastic anemia (SAA), including bone marrow failure caused by radiation sickness.
3. Malignant hematological diseases, such as acute leukemia, chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS), multiple myeloma, lymphoma, etc.
Third, the selection of bone marrow transplant donors.
Choosing a donor that is compatible with the recipient tissue is an important prerequisite to ensure the success of allogeneic bone marrow transplantation.
When choosing a suitable donor, first choose a donor from brothers and sisters; If not, look for donors among close relatives and unrelated volunteers. In the selection of donors, HLA was detected by serology in siblings first, and then D locus was detected by lymphocyte culture (MLC) to verify HLA matching. Even the differences of histocompatibility antigens that cannot be detected by serological or molecular biological methods can often be detected by MLC. At present, the direct detection of HLA genes by molecular genetic techniques such as polymerase chain reaction (PCR), sequence-specific oligonucleotide probe hybridization (SSOPA) and restriction fragment length polymorphism (RFLP) can be used as an important supplement to BMT tissue matching, especially for the verification of unrelated donor tissue matching.
Fourthly, the importance of HLA matching in bone marrow transplantation and the process of bone marrow transplantation
1. In HLA matching, there are mainly HLA-A, HLA-B and HLA-DR matching, and hematopoietic stem cell transplantation can only be carried out if the HLA matching of two individuals is completely the same, otherwise two situations may occur. First, the immune cells in the patient attack the implanted donor cells as "foreign bodies" or "intruders", which is called "transplant rejection". Another possibility is to implant donor hematopoietic cells into patients to produce a large number of immunocompetent cells. These cells attack patients' tissues and cells as "foreign bodies" and "intruders". The most vulnerable tissues and organs are skin, liver and intestine. Rash, jaundice, elevated transaminase and diarrhea are not just bloody stools. This is called graft versus host disease (GVHD), which can be fatal in severe cases.
2. Because the diversity of HLA-AB is the most obvious, volunteers usually use HLA-AB typing first, and then HLA-DR typing is performed on donors after HLA-AB matching of donors and recipients. If the donor and recipient HLA are completely matched and the donor health examination is qualified, the transplant operation can be prepared. Chemotherapy and radiotherapy are used to destroy diseased hematopoietic cells in patients before transplantation. Implantation is like blood transfusion. The implanted hematopoietic stem cells proliferate in the human body, rebuild the hematopoietic and immune systems, and the patients gradually return to health. The effective cure rate of bone marrow transplantation for leukemia can reach 65-75%.
HLA matching technology in bone marrow transplantation at home and abroad
1.HLA serological method
This method appeared earlier and the technology was mature. It is mainly used for typing HLA class ⅰ antigens (HLA-A and HLA-B), and is suitable for HLA-AB retrieval of a large number of bone marrow donor patients before bone marrow transplantation. However, in HLA-DR typing, because it is difficult to obtain high-quality stereotyped serum, there are cross-reactions, and there are differences in judging antigen specificity. The determination of serological phenotype is also influenced by the purity and vitality of isolated B lymphocytes and the quality of complement, which leads to a relatively high typing error rate.
2.HLA complex microsatellite analysis technology
In eukaryotic cells, some DNA components are obviously different from the main DNA components in base composition, and obvious bands can be separated by CsSI gradient centrifugation, of which 2 ~ 3 bases are microsatellite. Microsatellites can be repeated at different intervals and frequencies in eukaryotic autosomes, thus showing high polymorphism. This microsatellite repeat sequence has been located in or near the HLA gene complex. Therefore, sequence-specific primers can be used to determine the polymorphism of microsatellite by PCR amplification according to the length of the product.
Microsatellite analysis technology can quickly and accurately identify the similarities and differences of HLA haplotypes between donors and recipients, and because it contains a wider area of HLA complex, it may be more effective than the analysis of HLA-ⅰ or ⅱ unit allele, thus providing important parameters for the selection of donors in organ transplantation, especially bone marrow transplantation.
3.MHC fragment matching technology
The theoretical basis of block matching is that in the long-term evolution of MHC complexes, because the introns of MHC genes do not encode functional proteins, there is little pressure on their selection, so they are relatively stable relative to exons and can last for many generations without change. Research data have confirmed that an intron sequence may be common in a group of alleles. From the evolutionary and genetic point of view, such a group of alleles evolved from the same ancestral pedigree, and the common intron sequence is the specific marker of this pedigree. Therefore, different MHC alleles can be attributed to different families, and the difference of MHC gene sequence between different families is obviously greater than that within the same family.
Block matching is applied to random people for transplant matching, aiming at finding donors belonging to the same HLA pedigree as recipients and avoiding strong rejection after transplantation. The biggest advantage of this technology is not the matching of a single HLA gene, but the greatest similarity of the whole HLA haplotype gene sequence. Its practical application value has been initially confirmed in the family investigation of HLA polymorphism and the retrospective analysis of BMT curative effect.
Southern hospital has proved that not all patients with hematological tumors need bone marrow transplantation.
Chemotherapy can cure 80% of children with hematological tumors.
Generally speaking, many people think that bone marrow transplantation is necessary if they have leukemia. This is not the case! The reporter learned from the pediatrics department of Southern Hospital of the First Military Medical University yesterday that 80% of children with leukemia can be completely cured without bone marrow transplantation.
Yesterday, more than 70 leukemia rehabilitation patients who had been treated in the pediatrics department of the hospital returned to Nanfang Hospital to exchange anti-cancer experience, the youngest of whom was only over one year old. Seeing their innocence, you would never think that they have been suffering from blood cancer.
According to Li Chunfu, director of hematology department of Southern Hospital, the incidence of childhood leukemia is on the rise in recent years, but many people think that bone marrow transplantation is a necessary means to treat this disease. But clinical practice has proved that late chemotherapy is the most effective solution. "Hematopoietic stem cell transplantation is only regarded as a second-line treatment measure by European and American countries. It is only used for a very small number of high-risk or recurrent patients, and the cure rate of childhood leukemia in those countries has reached 80%! " After 4 years' observation, of 63 cases of acute lymphoblastic leukemia admitted to our hospital, only 2 cases recurred. There were 7 cases of acute non-lymphocytic leukemia, and 4 cases survived disease-free.
When the reporter asked the main reason why patients' concept of seeking medical treatment needs to be changed, Li Chunfu said: "Reasonable chemotherapy has been recognized internationally, which can greatly improve the cure rate and enhance patients' confidence; In addition, the treatment time is short, the side effects are less than those of bone marrow transplantation, and the medical expenses are low, which can reduce the pain and burden of patients. For example, the cost of chemotherapy is about 65,438+million, while the cost of bone marrow transplantation is at least about 200,000. " (Reporter Lin Jingjun Intern Ou Shigang Correspondent Ning Xiyuan)
Source: Yangcheng Evening News