One day in March 2007, just after the Chinese traditional festival, the Spring Festival, Wang Xiaohua (a pseudonym), who lives in Beijing’s Tongzhou District, began to feel weak all over, but she did not care, thinking she was tired during the Spring Festival. She is the eldest in the family, the following two sisters, the sisters have a good relationship, although they have become a family and have children, but every year the Spring Festival will gather in her family for the New Year, every time, the family inside and outside a dozen people eat and drink, will make her busy in the dark. She has a very tired feeling after the Spring Festival every year, she has some experience of this feeling, after the festival, always need to rest for a while to recover. But this year, she felt different from previous years, how can not rest over. A week later, she decided to go to the hospital to check …… to the hospital first check the blood routine, white blood cells 38 × 109 / liter, hemoglobin 124 g / liter, platelets 54 × 109 / liter. The first thing you need to do is to get a good idea of what you are getting into. That afternoon, Xiaohua was admitted to the hematology department, the same room with the patients are wearing masks “bald”. Soon, the doctor did a bone marrow aspiration test for her, although Xiaohua was very scared, but felt that the bone penetration did not hurt. After admission, Xiaohua’s two sisters and brother-in-law came to the hospital to visit her, everyone carefully accompanied themselves, and all wore masks? Xiaohua finally couldn’t help herself: “What disease do I have in the end? Is it leukemia? You guys don’t hide it from me, if it is, tell me, I’m not afraid ……”. Her husband and sisters turned their heads and shed tears. Yes, Xiaohua got the confirmation. “My child can’t live without its mother”, Xiaohua begged the doctor, “please save me ……”.
The current treatment options for leukemia are chemotherapy, hematopoietic stem cell transplantation, biomodulator therapy, gene therapy, Chinese medicine therapy and several others. Although there are various treatments, the main method is still regular and standardized chemotherapy. The chance of HLA matching is 25% in siblings and 1 in 100,000 in unrelated donors.
Xiaohua has two sisters, and she has a chance to find a suitable donor. However, she first had to undergo “remission induction” chemotherapy, and only after this phase of chemotherapy, the leukemia cells in her body were suppressed to a very low level (less than 5% in the bone marrow) before she had the basic conditions for transplantation. Wang Xiaohua underwent “remission induction” chemotherapy, achieved complete remission, and was lucky enough to be a match for his sister.
Xiaohua got up the courage and made up her mind to do the transplant, she inquired about what the hematopoietic stem cell transplant was all about. Where is the best place to do it and how to do it? Do you have to go into the operating room? Do I have to find a good surgeon? Through the internet and the doctors’ detailed introduction, she finally understood and firmly signed the transplant consent form.
Bone marrow transplant and hematopoietic stem cell transplant Why did Xiaohua have a hematopoietic stem cell transplant instead of a bone marrow transplant? Are they the same thing? Actually, these terms were developed in the course of transplantation. In the early days of transplantation, bone marrow was used as the raw material for transplantation, so it was called “bone marrow transplantation”. ” is a component of the bone marrow, which is present in the bone marrow and must be obtained by harvesting the bone marrow. With further understanding of bone marrow transplantation and the development of drugs, doctors are able to proliferate and release hematopoietic stem cells from the bone marrow into the peripheral blood by injecting granulocyte colony-stimulating factor into a healthy donor, then concentrating the hematopoietic stem cells from the donor’s peripheral blood for transplantation can avoid the pain of harvesting large amounts of bone marrow. Both transplantation methods have their advantages and disadvantages, but most hospitals perform “HSCT” in order to avoid the painful process of marrow harvesting for the donor.
According to the donor, HSCT can be divided into autologous transplantation, homozygous transplantation between identical twins, and homozygous allogeneic transplantation, which is further divided into sibling donor transplantation and non-blood donor transplantation. According to the source organ of hematopoietic stem cells can be divided into bone marrow transplantation, peripheral blood hematopoietic stem cell transplantation, fetal liver cell transplantation, and cord blood transplantation. According to the pre-treatment before transplantation, they can also be divided into purified marrow transplantation and non-purified marrow transplantation. Based on whether the graft is purified or not, it is classified as general hematopoietic stem cell transplantation, T-lymphocyte removal transplantation, and purified CD34+ cell transplantation. According to the degree of HLA (human leukocyte antigen) compatibility between donors and recipients, HLA-matched transplants, HLA-hypomatched transplants, and HLA-mismatched transplants can be classified.
According to the current medical treatment, the application of “HLA-compatible HSCT between siblings” can effectively produce anti-leukemia effects and is relatively safe for patients. Hematopoietic stem cell transplantation would be the best choice if the patient has a sibling and a match is found. However, the family planning policy in China makes most of the families only have one child, so the 25% match probability is lost, and on the other hand, the limited amount of specimens in the blood stem cell bank (bone marrow bank) is not enough to increase the 1/10,000 unrelated match probability. We all know that half of a child’s chromosomes come from the father and half from the mother, meaning that most patients can find at least one HLA hemizygous related donor. Therefore, parental HLA hemizygous transplantation is currently a hot topic of research, but also a difficult one.
Before hematopoietic stem cell transplantation, patients are subjected to pretreatment consisting of certain doses of chemotherapy and/or radiotherapy, usually for 6 to 9 days, to kill leukemia cells in the patient’s body and suppress the patient’s immunity, and then the collected donor hematopoietic stem cells are introduced into the recipient’s body through a vein. These cells are then released into the bloodstream and gradually create a donor-derived hematopoietic and immune system in the recipient’s body for the purpose of treating leukemia. By performing a hematopoietic stem cell transplant, the patient transplants the hematopoietic and immune systems of a healthy donor. This is a gradual process of building up and does not require the patient to enter the operating room, like other organ transplants that require surgical operations. The entire transplant process needs to be done in a sterile room to avoid bacterial, fungal and viral infections during a period of immune deficiency.
Choosing “Clear Marrow” or “Non-clear Marrow” Wang Xiaohua was fortunate to have a sister who matched his HLA and was medically qualified to be a blood stem cell donor. The next question was whether to choose a “clear marrow” transplant or a “non-clear marrow” transplant.
Traditional clear marrow transplantation uses high doses of radiation and chemotherapy as a pretreatment regimen, making the transplantation process very risky, such as longer periods of severe hematopoietic suppression that can cause cerebral hemorrhage, pulmonary hemorrhage and susceptibility to bacterial and fungal sepsis, often leading to early death of the patient; high doses of radiation therapy also tend to cause serious complications such as radiation pneumonia, hepatic vein occlusion syndrome and cataracts. In addition, the incidence of graft-versus-host disease (GVHD) is also high and severe; patients are slow to rebuild their immune function after transplantation and prone to recurrent various infections, which seriously affect the quality of patients’ survival after transplantation.
In contrast, non-cleared marrow HSCT discards the high-dose radiotherapy and chemotherapy pretreatment used in traditional transplantation, and mainly uses low toxicity and low side effects drugs or combined with low-dose radiotherapy (2 Gy) to form a pretreatment regimen, which is not only well tolerated by patients, but also has mild pretreatment-related complications; if a non-cleared marrow pretreatment regimen without radiotherapy is used, complications such as radiation pneumonia, cataract, reproductive Complications such as radiation pneumonia, cataracts, and reproductive dysfunction can be completely avoided with a non-cleared marrow pretreatment regimen without radiotherapy.
Compared with clear marrow transplantation, hematopoietic reconstitution after non-clear marrow transplantation is rapid, more than 10 or even 20 days earlier than clear marrow transplantation, which greatly shortens the myelosuppression period of patients and significantly reduces early mortality, making HSCT safer and less risky. More importantly, non-clear marrow transplantation has significantly reduced the incidence and severity of graft-versus-host disease after transplantation due to enhanced immunomodulatory treatment before and after transplantation, and more patients do not need to take long-term immunosuppressive drugs after transplantation, which accelerates immune reconstitution and improves the quality of life.
At present, non-cleared marrow transplantation has become one of the important directions of HSCT research, especially in the field of HLA-hemophilic HSCT research, the non-cleared marrow transplantation model is promising to solve the “bottleneck” that restricts HLA-hemophilic HSCT and make a breakthrough to effectively reduce the incidence of severe GVHD.
On September 29, 2007, Wang Xiaohua remembered this date forever. In her own words, it was the day she was reborn and her second birthday. Xiaohua opted for the “non-purge” pretreatment, and the process went so smoothly that she did not feel like she was going through a “phoenix nirvana”. When she watched the blood stem cells donated to her by her biological sister slowly flowing into her body while lying in the sterile ward, her eyes could not help but moisten and shine with tears of hope.
Ten days after the transplant the hematopoiesis started to recover and she stepped out of the sterile ward smoothly, with the confidence of regaining the flower of life. Now, it has been nearly one year since Wang Xiaohua’s transplant, her oral anti-rejection medication has been reduced and stopped, she is able to take care of herself and gradually perform some light work, and new hair has sprouted on her head, darker and brighter than before, with a slight curl…