Hematology and Oncology Center pediatric and Adult (stem cell transition – bone marrow transplant)
Hematology and Oncology Center pediatric and Adult (stem cell transition – bone marrow transplant)
The bone marrow transplant center (stem cells) is one of the most important forms of the hematology treatment such as, Thalassemia, sickle cell anemia, aplastic anemia, Myelodysplastic syndrome, and malignant diseases such as leukemia, lymphoma and solid tumors, treatment of weakened immunity and some metabolic diseases.
Every day a new group of diseases is added to the list of diseases that are used in the treatment of stem cell transplant. In our country with a population of 75 million people, Stem cell transplant is carried out to 3000 patients every year. In many centers, patients wait several months until their turn comes. Pediatric bone marrow transplant center in our institution, the bone marrow and stem cells transplant center is licensed by the Ministry of Health and is one of the largest centers of blood tumors for treatment in the field of bone marrow transplant.
Our Pediatric bone marrow transplant center is the largest bone marrow transplant centres in Turkey with 17 single rooms. The area of the rooms ranges from 22-30 square meters. 5 rooms will be used as intensive care rooms but in all the rooms there is an infrastructure for intensive care. Patients from the nurse room will be monitored 24 hours a day through the monitoring system.
The clean air system in the rooms:
In the patient rooms, there is HEPA filter system, the type of roof that is applied for the first time in our country through the use of HEPA fan units and air flow techniques. The type of mixed flow has been applied to achieve prevention at the highest levels against infection diseases which are transmitted through the air. In this type of flow, a spectral air flow is applied over the patient, and a corrugated air flows in the other areas of the room but the spectral air flow that is applied on the patient’s bed surfaces and the shape of the velocity formed near the bed is regulated so as not to disturb the patient permanently. As for the pressure, it was set for the air, so it flows from the patient’s room to the external passages.
The benefits of this system:
- The pressure of each room is separately adjustable to the required level and in this manner, there are no pressure problems with the centralized single channel systems.
- Thanks to the separate air system which does not infect other rooms by mixing germs into the system.
- It operates with power saving mode in the rooms where there are no patients and provides high power saving.
- The amount of air transfers per hour per room is adjustable between 10 – 18 ach
- High-performance filtration (%99.97 0.3 µm) achieved through a system Purification HEPA
- The risk of infection because of ventilation has been completely eliminated the technology of non-leakage and passive plutonium.
- No polluted air is crossed into the patient’s room, especially from hanging ceilings and from the surroundings.
- UV sterilization is continuously performed.
What is the bone marrow transplant?
Bone marrow transplant, umbilical cord blood, or stem cell transplant is a procedure that aims to replace damaged bone marrow with the donor’s bone marrow. We can use it to treat patients with:
- Life-threatening cancers such as leukemia.
- Diseases that result in bone marrow failure, such as aplastic anemia
- Other immunological and genetic diseases.
Research on bone marrow transplant has improved the survival rate over time, which in turn has helped many patients using this treatment. Bone marrow transplant is the only cure for many diseases.
The bone marrow is soft spongy tissue, called the red marrow, which located inside the bone portion known as sponge bone, whose primary function is the production of blood cells, and consists of anaplastic cells (it turns into bloody cells) it is a hematopoietic generator and a fat cell, and tissues that help the growth of blood cells.
The anaplastic cells at the beginning of formation (primary) are called blast cells or stem cells, and they continuously divide themselves to multiply, producing new stem cells, part of them remains the same as generating structural cells that continue to reproduce while the other part stops producing and it goes through a series of cumulative transformations and divisions and successive stages of development, to mature transforming into the different blood cells (white and red blood pellets and platelets), which in turn continue their growth and maturity stages inside the marrow before moving to the blood circulation to perform their functions, (and some of the white pellets known as lymphocytes continue the full growth in the lymphatic glands, spleen, and thymus). The bone marrow is found in almost all the bones in infants, while before puberty, it is often in the flat bones, such as the skull bone, shoulders, and ribs, pelvic bones, arm and leg joints.
The need for the bone marrow transplant treatment (bone marrow transplant) and stem cell transplant comes when the bone marrow becomes unable to perform its functions and produce blood cells, whether as a result of its damage due to cancer itself (which makes it either a producer of abnormal tumor cells or a producer of small numbers of blood cells), or due to the effects of the severe chemical drugs and radiotherapy on the marrow, it may be necessary to eliminate the cancerous cells, especially in cases of blood tumors, lymphoma and some solid tumors, strong treatment programs with intensive doses destroy and thwart the marrow and lose its ability to perform its functions, therefore, transplants are intended for replacing the stem cells with the cancer-infected marrow or frustrated because of treatments, with healthy cells that can grow, reproduce, and produce blood cells.
It is worth noting that transplants were initially used experimentally to treat people who were exposed to radiotherapy as a result of nuclear accidents, and then it turned out to be effective in treating various tumors, we also point out that the transplant is an intensive and multifaceted process that affects all parts of the body, and has many implications, complications and high risks, we may lose the patient despite the success of the transplants completely, which depends on multiple factors, such as the patient’s age, general physical condition, type of tumor and its stage, and there are no guarantees or predictions about success or failure, despite the high success rates of transplant, especially with children.
Collecting the stem cells:
The stem cells are collected from the bone marrow, the circulatory system, and newly from the umbilical cord of newborns.
Collecting the stem cells from the bone marrow:
The bone marrow is the main source of the stem cell transplants, and the process of extracting the bone marrow and collecting it called the harvesting , it is usually conducted under the general anesthesia to the donor, who in turn is subject to a set of analyzes and tests, to ensure the level of his general health and in particular naturally to make sure that he is not infected with infectious diseases, especially to make sure that the blood is free from infectious viruses such as HIV/AIDS or hepatitis virus. About one liter of bone marrow is collected directly from the hip bone using a special needle and under complete sterilization, (and naturally the amount collected is proportional with the size of the recipient patient, as adults need more than the children need), and this process usually does not take more than one hour, and the donor’s body compensates the extracted amount very quickly because it is little, and it is customary to take a unit of the donor’s blood a week before the operation and then transfer it to him/her after his donation to compensate the deficiency, and the donor usually leaves the hospital the next day, without any complications except the feeling with some temporary fatigue.
After the collecting, blood compounds and bone impurities are separated from the marrow, and then kept in special packages, and the stem cells are selected and collected separately, and in turn are injected to the recipient with some of the selected cells within a period not exceeding 24 hours, it is worth noting it is possible to preserve the marrow for years if necessary, by placing it in special preservatives and freezing it using liquid nitrogen to keep the stem cells alive. This method is used especially when the marrow is collected from the patient him/her self, and this is achieved between two treatment cycles when stabilizing and freedom from the carcinogenic cells, so that it can be returned if there is any future relapse.
From the blood circulation
There are few numbers of stem cells in the circulatory system, and in this case they are called peripheral stem cells, which are not usually sufficient for harvesting for the patients, and their use for transplant becomes practical when the patient has the ability to induce the bone marrow to be excreted in the bloodstream in sufficient quantities, and there are a number of ways to do this, including using stimulating growth factors individually by injecting them subcutaneous, or by adding a small dose of chemical drugs. While when collecting periodic stem cells from donors, they are collected from the blood circulation of the donor by passing blood through a special filter machine that separates these cells from other blood cells, and returns the blood to the blood circulation at the same time, and this process usually takes between one to two hours for two consecutive sessions within two days, it is a safe and painless process and does not require anesthesia, and without any risk of infection as all tubes and connections are used only once.
On the other hand, most patients spend less time into the hospital after stem cells transplant, and the rate of complications decreases, as the count of white blood cell and platelet return to the normal quantum more quickly.
Collecting the stem cells from the umbilical cord of newborns.
The umbilical cord of newborns contains huge numbers of stem cells, and medical studies are conducted in order to use them in transplant processes, and it is hoped that the risk of complications from transplant or rejection will reduce as these cells are not exposed to external stimuli, and we note that most transplants from this source was conducted for children who are siblings of the newborns who will donate, and research is still ongoing to use this infinite resource with adult patients and patients without kinship, which may solve the problem of finding a matching donor.
Choosing the donor
The patient him/her self may be the source of the stem cells, or one of his relatives and usually one of his siblings, or with a non-kin donor, and the appropriate donor is chosen after performing a special histological analysis of the blood, known as HLA- Human leukocyte antigen, and this analysis aims to match the genetic codes of the proteins of the characteristics of the white blood cells that are found on their surfaces as distinctive characteristics, and thus determining the extent of possible immune interaction about them, and the success of transplant depends on the extent of the tissue matching between the donor and the recipient, and the ideal matching is that which combines six classes of these proteins, most transplant centers require at least five of them to be matched, in anticipation of possible rejection of the body either toward transplanted cells, or of those cells that may attack the tissue of the body as alien.
Types of bone marrow transplant treatments pediatric and adults:
Bone marrow transplant pediatric and adults from the patient him/her self – Autologous transplant
The bone marrow or periodic stem cells of the patient him/her self can be used in some cases, and one of the conditions that must be met here is that the number of healthy stem cells is sufficient for transplant, and that the patient be in a state of stability and freedom from tumor cells in a large percentage, and the autologous transplant operations are conducted in a way that the stem cells are harvested and meticulously processed to eliminate the remaining tumor cells with a complete disinfection process, and then returned to the body, (in this case there are no risks of rejection in practice), and disinfection processes are carried out following one of two ways, either using drugs and antibodies to isolate the stem cells then returning them fertilized to the body known as the way of positive selection, or using anti-particles against tumor cells and removing them from the extracted marrow then the stem cells are returned to the body, and this is known as the method of negative selection, and recent developments in labs analyzes and tests have helped to determine accurately the remaining small numbers of cancer cells in the maximum use of the disinfection process.
Allogeneic bone marrow transplant pediatric and adult:
The bone marrow comes from a non-patient from relativistic transplants donors, and the success of this transplant depends on the match of the aforementioned tissues, where all the tissues of the body carry genetic codes that determine to the immune system the identity of the tissue or cells, whether they are self or foreign (Such as bacteria), and the immune system attacks the transplanted stem cells and rejects them unless they have fully or partially identical tissue, and the opposite may occur, that is, the immune reaction of the transplanted cells against the recipient’s body tissue.
The identical twin sibling is considered an ideal donor, if twins’ transplant is rare, and there are no problems in terms of immune reaction in such a case, and if the transplant may fail for other reasons naturally, the next best donor is a fully identical sibling whether male or female, the chance to have this donor is usually 1/4, depending on the average size of the families.
As for the non-kin donor, there may be a donor with identical tissue having the same required codes, or some non-identical codes may be overlooked when we have to due to the lack of a fully identical donor, and we note that there are several blood banks in the world that register millions of donors and keep their tissue analyzes, enabling the identical non-kin donor to be found when not available in the family members.
Transplant indications
Treatment of different tumors (especially blood tumors that do not respond to standard treatments) is the main indication for transplant, in addition to the occurrence of relapses and the return of such tumors again after the success of the initial standard treatments with varying time periods, and the eligibility for transplant depends primarily on the general health level of the patient, and that should be at a level capable of tolerating high doses of anti-cancer drugs and radiotherapy, and in this regard the patient’s age is one of the important factors, as the success rates of transplant in young people significantly exceed those of adults, and for this reason some transplant centers require that the patient age category should be below fifty years to make any transplant.
We review below an overview of oncology, hematology and immune system diseases that benefit from transplant:
For acute leukemia, transplant may not be necessary for cases that have shown good response to standard treatment plans, the transplant is limited for very few children suffering from acute lymphocytic leukemia, due to the possibility of controlling the tumor with chemotherapy only, while transplant may be recommended for the category of children with weak response and with adults, upon reaching the first stage of stability and complete inactivity in which blood and bone marrow are free from cancerous cells, on the other hand transplant is recommended when relapse occurs in children while receiving treatment cycles provided that stability is restored again.
Whereas acute myeloid leukemia cases, which are classified into three categories according to the standard treatment response pattern, good, standard or weak response, the course of treatment can be predicted according to this classification, where good response cases have a high chance of recovering by standard treatment and not candidate for transplant, while most cases of weak response (and who usually do not achieve long periods of stability) are nominated, as for standard response cases, it is difficult to predict the extent of their need for transplant and the decision is made according to the personal factors of each case individually.
It is not usual to recommend transplant for cases of chronic leukemia that are not common with children, due to its slow development, except in cases of chronic myeloid leukemia that are not responding to chemotherapy or biological treatment for long periods, or in some cases of the accelerated and acute phase of this leukemia.
On the other hand, in cases of leukemia-related disorders, such as myelofibrosis, or myelodysplastic syndromes, they are not nominated for transplant, except in severe cases of aplastic anemia and cytopenia, which transplants have achieved good results in treating them.
With regard to cases of lymphoma, transplant is usually not recommended for Hodgkin’s disease, except for cases that are resistant to treatments. In this case, Autologous transplant is usually recommended due to its very encouraging results, whereas in cases of Non-Hodgkin lymphoma, Autologous transplant is not usually recommended. Stem cells transplant is preferable that have achieved long periods of stability without achieving complete recovery.
Clinical studies are still underway to assess the effectiveness of transplant in cases of pediatric solid tumors, especially Retinoblastoma and Neuroblastoma, and transplant may be recommended in cases of treatment-resistant solid tumors, which require intensive treatments at high doses to control them, such as rhabdomyosarcoma.
Transplant procedures
Initial analyzes
Two to four weeks before the date of transplant, the patient will undergo various lab analyzes and tests that are comprehensive for the whole body, especially the heart, lung, kidney, and liver tests in addition to the mouth and teeth, and the transplant plan is arranged based on the results of these analyzes, in addition to the history of the disease and the treatment courses received, and naturally, various and comprehensive tests and analyzes continue such as blood tests, x-rays, bone marrow scans and others throughout the treatment period, and it is obvious that the patient should be isolated in a protected environment in a special room, with taking all necessary precautions to isolate it from the external environment, in particular precautions to prevent infection, for example, the family and the medical team should wear masks when entering the patient’s room, and they always sterilize their hands, and it is prohibited to bring fresh fruits or flowers, etc., and the visits of strangers are prohibited, especially those with contagious diseases such as influenza.
Installing the venous catheter to the patient
Before starting the transplant, it is necessary to perform a surgery to install a main venous catheter, usually in the chest, for the need to use it in injecting various drugs, antibiotics, and supporting compounds, in addition to the transplant process itself, and taking analyses samples throughout the treatment period, and the catheter usually remain transplanted for several months, and patient’s family are taught how to care it after leaving the hospital , and sterilizing it to avoid the emergence of infections to them.
Treatment of the patient to remove a disease from the body
The patient undergoes an intensive initialization process in preparation for the transplant, the initialization processes contemplate two goals, thwarting the immune system to reduce the chances of the rejection of the transplanted cells, and intensive treatment to eliminate any remaining tumor cells to reduce the chances of the tumor return later, and at the same time the initialization process destroys healthy marrow cells, which leaves space for the transplanted cells to occupy their own places that are necessary for them to settle and grow.
The initialization process are carried out using high doses of chemotherapy drugs, in addition to the use of radiotherapy for the entire body or without it, and there are several standard treatment plans followed in the initialization process, change depending on the types of the tumors and transplant, and in general two treatment systems are used, either by using two chemotherapy drugs together, such as Cyclophosphamide or Busulfan, Cytarabine or Etoposide, or by using one drug with total body irradiation, the use of total – body radiotherapy is not essential for all cases, and is performed in different doses depending on the situation and at a rate that changes from one treatment plan to another, And it is mostly performed in two treatment sessions per day, for several days, and in small doses to reduce the risk of complications and side effects.
The transplant process:
The transplant of marrow or stem cells is simple as such, as it is similar to normal blood transfusions, where it is injected intravenously or via a catheter, and the patient is monitored in anticipation of the symptoms of allergic reactions, rash, fever, or hypotension, and patients usually do not encounter no hassles when injecting.
As soon as the stem cells enter the blood circulation, they take their way into the bone marrow and settle into the vacuoles of the bones (especially the large ones) and begin to organize themselves to begin the production of blood cells. Usually, the effects of the process of initialization and chemical drugs begin to appear during the second or third day of transplant (especially the effects of bone marrow thwarting), which requires keeping the patient under close observation.
The beginning of production is called engraftment stage, and it often occurs within two to six weeks after transplant. It is customary that blood count analyzes determine the start of white blood cells production and then the platelets and then the red blood cells, which will confirm the success of the transplant, and naturally, the patient undergoes during this period to various analyzes and lab tests to ensure the efficiency of the main vital organs of the body, such as the heart, lung, and kidneys. The patient also receives the necessary nutrition intravenously to ensure food adequacy.
On the other hand, the full recovery may take between one to two years, and doctors perform various blood analyzes and conduct bone marrow exploration periodically to investigate the efficiency of the transplanted marrow.
The intensive care
The intensive care and body support processes is one of the most important elements in transplant operations, and its primary goal is to manage the complications and multiple side effects of high doses of chemotherapy or radiotherapy, whether by taking the special measures by avoiding them or reducing their effects or treatment.
These effects include thwarting immune system, anemia, and easy bleeding, due to a decrease in the rates of different blood cells, in addition to mouth complications, nausea and vomiting problems, nutritional complications and anorexia, due to the sensitivity of the digestive system, and finally the problems of deficiency in the functions of the main organs, such as the lung, liver, kidneys and heart because of their damage.
Thwarting immune system is one of the most important serious complications, as the body loses its defense capabilities against any infection, and the intensive care is represented in this case by placing the patient in a well-protected environment and completely isolated from exposure to infection factors, and then the starting of taking antibiotics and anti-infection Viral, in addition to antifungals in anticipation of any possible infection, in addition to immunotherapy, which represents in the separation and collection of Alien antibodies from the donor’s blood and then inject them into the patient in an additional effort to support immunity, and such care begins from the moment thwarting the patient’s marrow until checking the ability of the transplanted marrow to the production of a sufficient number of white blood cells.
In most cases, factors stimulating growth are given to accelerate engraftment and start production and to reduce the risk of infection or the risk of transplant failure, as the body is supported by regular blood transfusions, to treat anemia and a lack of platelets, (after exposing blood transfused to radioactive doses, which destroys in particular, lymphocytes that may attack the cells of the patient’s body).
On the other hand, the nutrition system is one of the most important factors in the intensive care, and it is customary to use non-enteral nutrition to give the patient his nutritional needs intravenously and in calculated doses, for two main reasons: The first is that chemotherapy and radiotherapy cause nausea, vomiting, and mouth inflammation which makes the eating process itself painful, and the second is that the treatment program requires stopping eating for a while, to allow the organs of the digestive system to recover after receiving high doses of chemical drugs.
Most patients stay in the hospital for a period of one to two months after transplant to ensure the success of the operation, and for the treatment of any complications that may appear, and it is usually allowed to the patients to leave when the number of neutrophils in white blood cells exceeded the rate of 500 in the standard blood count, for two consecutive days taking into account many other factors, such as a red blood cells count, platelets count, and freedom from infection, in addition to the general health level of the patient, and it is customary for patients to need regular blood transfusions after leaving the hospital, which requires the catheter to remain in its place for periods ranging from three to six months, and naturally Periodic checks are performed on patients and with a specific time schedule, and the patient is examined daily after leaving the hospital and throughout the first two weeks, then tests are conducted weekly throughout the first months, to ensure that the body produces blood cells at normal rates, in addition to investigating the occurrence of any carcinogen again, especially by exploring the bone marrow periodically to monitor it.
Risks and complications of stem cell transplants
Risks and complications related to transplants can be classified into two parts:
early or short-term, late or long-term complications: short-term risks and complications – early minor complications.
Patients often experience several complications after transplant, some of them temporary and minor and some of them is considered life threatening, and the severity of serious complications depends on several factors, such as the patient’s age and general health condition before transplant, and it is common for minor, temporary, and common complications to appear when receiving chemotherapies and radiotherapies that include hair loss, nausea , vomiting , fatigue , physical fatigue, anorexia, mouth inflammation and skin allergy.
It should be noted that there are side effects of some of the drugs used to treat the mentioned complications, including intestinal problems, hypertension, and in some cases neurological attacks or impaired vision for example, as well as with stimulating growth factors that in turn cause side effects including bone and muscle pain and flu-like symptoms, and we point out that the severity of all these effects varies from person to person.
The bone marrow produces the cells of the immune system that develop from the stem cells, which means that the cells of the patient’s immune system will be produced from the donor’s grafted stem cells, and in all cases, except identical twins transplants, the tissue matching is partial and not entire, which means that the risk lies in the possibility of attacking the transplanted grafted immune cells to tissues of the patient’s body tissues and cells ,considered as foreign bodies.
This condition is known as Graft versus host disease and is considered acute and life-threatening if it significantly occurs during the first hundred days after transplant, and is considered not severe if it occurs after that, and this immune reaction arises when the transplanted immune cells, especially T lymphocytes, examine the patient’s cells in search of differences in genes and attacking them as enemy bodies if there are large differences, and here the importance of histological analysis of genetic codes lies referred to previously to find the matched donor.
It is customary that the first severe signs appear in the palms and soles, such as allergy, itching, burning and redness, and then spread on the entire skin, and some small pimples and crusts may appear, and one of the symptoms that follows is the emergence of nausea, vomiting, intestinal spasms, anorexia and diarrhea. On the other hand, yellowing of the skin and intestinal pain is evidence that the liver is affected, which may swell in turn, and these symptoms may be moderate or severe or life-threatening when branched, which is difficult to control.
As for its non-acute or chronic phase, which usually appears after the third month of transplant (and may not develop even after a year), most patients suffer from skin problems, starting with allergy and itching, and the skin may become curved and rough and it has a dark color, and hair loss may accompany it, and the mouth and esophagus may experience severe dehydration and inflammation, and ulcers may arise, (and the lung may also be affected by dehydration), as the liver may be damaged and failure to perform its functions may occur, and bile flowing to the blood leads to the emergence of jaundice in turn.
About nutrition program and diet
It is especially important to monitor the patient’s nutrition completely, and the diet should mainly consist of fresh and perfectly cooked food, and it does not contain any spices like pepper, and it is acceptable to eat ready-made sterile and well-wrapped foods such as butter and processed cheeses or biscuits, as well as toast and not fresh bread, and newly-opened canned fruits, as for cold meats , various uncooked salads and fresh fruits, they should be avoided, just as it is completely prevented drinking water from the tap or mineral water, only sterile water and reliable source water is allowed, which is also used to cook the patient’s foods or to prepare drinks, etc., as well as sterile milk and it should be taken into account that the can has not be opened for more than one day ago and kept in the refrigerator all the time, and food restrictions may be eased when the end of the first six months, and the expansion of eating different foods according to the patient’s condition progress.
Leaving the hospital
According to the regulations used by most transplant centers, most patients recover sufficiently to allow them to leave the hospital within a period of three to five weeks, and it is traditionally recommended to leave when the bone marrow produces enough quantities of healthy blood cells completely, and there are no complications after transplant, and naturally the recovery period varies from patient to another, and it is customary for patients to feel significantly better when blood cell production returns to normal, and some symptoms begin to stop, such as mouth inflammation, diarrhea, nausea or vomiting, and symptoms of fever also stop and appetite improve, and it is necessary in this regard to ensure the recovery of edibility before departure and that the body has sufficient nutrients and fluids.
The patient continues the recuperation at home, and the family is provided with the necessary instructions to continue care, such as observing symptoms that require the rapid return to the hospital such as fever, diarrhea, or any pain, and the weekly and monthly review schedules and so on are clarified, and in most cases, the recuperation period requires from six months to a year until blood production returns to normal rates. During this period, the patient should be prevented from being present in gathering places such as markets and others, or contacting other patients who carry infectious diseases such as influenza to avoid catching infection, and sick children should also be prevented from mixing with other children who have just been vaccinated with live vaccines, and all precautions are taken to avoid wounds or continuous exposure to sunlight.
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