Pediatric Bone Marrow Transplant Unit

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About the Department

Among the most important life threatening diseases in childhood, "blood diseases" ranks first. Accordingly, every year thousands of children in Turkey is diagnosed with blood cancer. Pediatric bone marrow transplantation is also very important in this direction. Early diagnosis and correct treatment are of great importance for the successful treatment of blood diseases that may require bone marrow transplantation, especially leukemias.

The most important way to be successful in the treatment of pediatric blood diseases and in bone marrow transplantation is through the treatment of patients in fully equipped centers with their infrastructure and service quality. Memorial Ankara Hospital Pediatric Bone Marrow Transplant Unit established for this purpose serves children with SSI assurance and high-level diagnosis and treatment opportunities.

What is Stem Cell?

Stem cell is the special name given to the leading cells that show the capacity of the body to transform into other cells.

These cells are;

  • It settles in a suitable environment for them.
  • It has the ability to reproduce.
  • It can be transformed into other types of cells and can then multiply as such cells.
  • They can renew themselves or maintain their own cell communities.
  • It has the capacity to repair the damaged body and make it work again.

“Hematopoietic / Blood” stem cells, which are responsible for blood production, are the most known and most commonly used in treatment. 

What is Hematopoietic Stem Cell Transplant / Bone Marrow Transplant in Children?

This treatment method is called bone marrow transplant. Hematopoietic / Blood stem cells obtained from different sources in the treatment of Pediatric Bone Marrow Transplantation are given to patients who need it for a variety of reasons, similar to a blood transfusion.

How to Obtain Hematopoietic Stem Cells?

Cells used for bone marrow transplantation in children can be obtained from three different sources.

• Bone marrow

Blood circulating in the veins (peripheral blood)

• Umbilical cord blood taken from newborns

Stem cells from the bone marrow are increasingly used and are replaced by peripheral stem cells.

How to get stem cells from bone marrow?

The bone marrow is located within the spongy spaces inside the bones. It works for the production of platelets that stop bleeding in the blood, white blood cells necessary for the immune system and red blood cells that carry oxygen throughout our body.

The most common location of the bone marrow is the pelvis (pelvis) bone of the human body. The removal of the bone marrow required for transplantation from the donor is performed under general anesthesia and in a sterile environment. Thus, the pain of the donor is prevented. The transmitter can be discharged after being kept under observation for 24 hours after collection. Special needles are used to collect the buttonhole. These needles allow pulling a dense thick marrow.

The collected marrow is passed through special filters to separate the fat and small pieces of bone that may have gotten into the marrow. If it will not be used immediately, it is placed in special liquids and frozen. When it is used, it is thawed and given to the patient in a similar way to a blood transfusion. These blood stem cells, which enter the patient's body, settle in the bone marrow and usually begin the production of blood cells within 2-4 weeks.

How to get stem cells from peripheral blood?

Normally, the amount of stem cells in the blood circulating in the vessels is low. For this reason, donors use drugs to increase the amount before collecting. These drugs are called growth factors. Thus, the proliferation and mixing of stem cells in the bone marrow is accelerated. Peripheral stem cells are separated from donor's blood with special devices. The blood, other than the separated stem cells, is returned to the person. This process takes about 4-6 hours. Depending on the amount of stem cells required for the patient, the procedure may need to be repeated for several days in a row. In the so-called autologous transplant, the peripheral stem cell donor is the patient. Collected stem cells are frozen in special bags until they are used. When it is used, it is thawed and given to the patient in a similar way to a blood transfusion. These blood stem cells, which enter the patient's body, settle in the bone marrow. In this type of transplant, blood production starts earlier than the bone marrow and takes place in a period of 10-20 days.

How are Cord Blood Stem Cells Obtained?

Umbilical cord blood is collected from the umbilical cord or placenta after the baby is born. This blood is rich in blood-forming cells. The donated blood is tested from various angles and stored for future use when needed. Storage units created for this purpose are called umbilical blood banks. Doctors seek a suitable tissue group match by contacting these banks when needed. If a belly blood that meets these conditions is found, the transplant is performed in a similar way to others.

Who Can Transplant With Cord Blood?

Cord blood is transmitted to children mostly because it contains a limited number of stem cells. In people with high body weight, sometimes two or more cord blood can be combined and transplanted. The ideal stem cell source is compatible with tissue groups. However, in transplants with cord blood, transplantation can be performed although it is less compatible. This option comes up especially in people with rare tissue groups. Cord blood is kept ready as stored. Therefore, it can be delivered to the transplant center in less than 2 weeks. However, it may take 2 months or more to find an unrelated stem cell donor. If urgent transplantation is required, cord blood is preferred. “Graft Versus Host Disease” is a side effect that can be observed in the patient after the transplant, and it is less frequent and less severe in transplants with cord blood. However, the low number of stem cells in cord blood, the time it takes for the formation of new blood cells, and the absence of replacement if the patient needs to be transported again leads to the fact that cord blood is a less preferred source of stem cells. Ultimately, the transplant doctor must decide which stem cell source is the most suitable option.

What is Allogeneic Stem Cell Transplantation?

In this type of stem cell transplant, stem cells are obtained from another source, not from the patient himself. The preferred HLA tissue group is to transplant from a compatible sibling or relative. Otherwise, transfer from alternative donors should come to the agenda. For this purpose, HLA compatible non-relative bone marrow donor screening is performed first. These people are called bone marrow / stem cell donors. If there is no non-relative donor, non-relative cord blood is investigated. When all of these resources are consumed, HLA incompatible or haploidentic stem cell transplants can be performed as an alternative stem cell source. Today, the scientific process should be this way.

In allogeneic stem cell transplant, donor stem cells form their own immune cells in the patient's body. This helps to eliminate cancer cells that may remain in the body, especially despite chemotherapy. Another advantage is that this type of transplantation can be treated with more stem cells. In addition, because donors are healthy, the stem cells they donate do not contain cancer cells.

However, there are some problems that may arise in allogenic transport. The first of these problems is the so-called graft failure. Transplanted cells can be eliminated by the recipient's body before they settle in the patient's bone marrow. Another problem is when the donor's immune cells attack the patient's body. This condition is called graft-versus-host disease. In addition, due to the drugs used for transplant and drugs that will prevent rejection of the given stem cell, the patient's immune system is suppressed, and some factors, especially in his body, can cause serious infections.

Which diseases are most common in childhood, allogeneic stem cells are transplanted?

Allogeneic transplantation is performed to non-malignant diseases that are malignant or mostly hereditary in childhood. The most common transplants of these diseases can be listed as follows:

  • Leukemia
  • Myelodysplastic Syndrome
  • Aplastic Mom
  • Paroxysmal Nocturnal Hemoglobinuria
  • Fanconi Aplastic Anemia
  • Thalassemia
  • Sickle Cell Anemia
  • Severe Combined Immune Deficiencies
  • Wiskott-Aldrich Syndrome
  • Hemophagocytic Lymphohistiocytosis
  • Kostmann Disease
  • Chronic Granulomatous Disease
  • osteopetrosis
  • Mucopolysaccharidosis
  • Adrenoleukodystrophy
  • Metachromatic Leukodystrophy (MLD)
  • Globoid cell leukodystrophy (Krabbe)

Wolman disease

  • mannosides
  • Structural Aplastic Anemias: Diskeratosis Congenita, Scwachman-Diamond Syndrome, Amegakaryocytic thrombocytopenia
  • Diamond-Blackfan Anemia

These diseases are diagnosed by bone marrow aspiration and / or biopsy as well as detailed history and physical examination.

What is Autologous Stem Cell Transplantation?

In this transplant type, unlike allogeneic stem cell transplant, the stem cell source is the patient itself. Firstly, the patient regression is evaluated after taking a certain number of chemotherapy cures depending on the type of the disease. The most important point in this evaluation is the absence of the disease in the patient's bone marrow. If the disease is not detected in the bone marrow, drugs with G-CSF active substance are applied under the skin in the morning and evening to increase the number of stem cells. The number of CD34 positive cells in 2-3 ml of blood is examined in the period when the blood count is observed every other day and the number of leukocytes starts to increase after the fall. If the CD34 number is above a certain value, stem cells are collected by apheresis method.

When are the collected stem cells transplanted to the patient?

Autologous stem cell transplantation is not usually done immediately after stem cell harvesting. The collected stem cells are mixed with the solution called DMSO to a certain extent, and then stored in nitrogen tanks until they are transported. After these frozen stem cells are thawed in suitable hot water tanks just before the transplant, they are administered intravenously to the patient as if they were blood transfused.

Which method are stem cells collected?

In autologous transplantation, the patient's stem cells are mostly collected by apheresis method. A double lumen catheter is inserted into the patient's neck or inguinal vein to make apheresis. This catheter is connected to the apheresis device and stem cell collection is started from the patient. This process takes about 5-6 hours and is easily performed on the patient's own bed. During the procedure, the patient is monitored and all vital functions are closely monitored. Stem cells collected after apheresis are stored and frozen in nitrogen tanks after certain processes.

When is stem cell transplant done?

The patient receives a certain number of chemotherapy depending on his illness, and then the disease state is evaluated. If the disease is in complete remission, that is, if all the visible disease has disappeared, then stem cell transplantation is performed. The basic logic in autologous stem cell transplantation is to eliminate the disease completely with high-dose chemotherapy, ie without a single malignant tumor cell. To achieve this, combined chemotherapy drugs called disease preparation regimen are used. Due to this high dose of chemotherapy, erythrocytes, leukocytes and platelets become unproductive in the bone marrow. In this process, intensive supportive treatments are applied to the patient.

The preparatory regimen can be defined as the combined application of different chemotherapy drugs selected depending on the disease. Before the patient is given this chemotherapy, in other words, before the autologous stem cell transplant, the patient is evaluated in detail. In this evaluation, the patient's kidney and liver functions, heart and lung health are examined, and the endocrine system, immune system, eye and other systems are evaluated in detail and recorded. After plenty of fluid support, the patient is given intravenously on certain days in accordance with the rules of each chemotherapy drug. Subsequently, stem cell transplantation is performed and today it is considered as the 0th day of stem cell transplantation. Afterwards, intensive supportive treatments are applied. The first two weeks after stem cell transplantation are very critical and especially bone marrow engraftment, that is the involvement of the bone marrow, occurs within this period.

In the process after the stem cell transplant, blood products are transfused according to the need. The patient is highly protected against infections. However, patients may still have fever and need to use antibiotics intravenously. Nutrition of the patient is closely monitored and supported. Some medications can be used for bone marrow engraftment. In this process, the patient is closely and dynamically monitored, and possible complications developed by daily examinations are tried to be identified early. In addition, the patient is provided with social and psychological support at every stage of these processes.

After autologous stem cell transplantation, the patient is closely monitored. Occasional blood tests, imaging tests are performed to evaluate the disease status and all body systems are examined in detail. The problems identified are tried to be solved with a multidisciplinary approach with the support of the relevant departments.

For which diseases are autologous stem cells transplanted most frequently in childhood?

Diseases undergoing autologous bone marrow transplantation can be listed as follows:

  • Acute Myeloid Leukemia
  • Non-Hodgkin's Lymphoma
  • Hodgkin Lymphoma
  • Neuroblastoma

Ewing sarcoma

  • Medulloblastoma (from brain tumors)
  • Soft Tissue Tumors
  • Germ Cell Tumors
  • Wilm’s Tumor (kidney tumor)
  • Retinoblastoma (eye tumor)

Some autoimmune diseases

What are the Symptoms of Childhood Leukemia?

Among malignant hematological diseases, leukemia is the most common form of childhood cancers. Leukemia affects the reproduction and function of blood cells. Stem cells in the bone marrow mature and turn into erythrocytes, leukocytes or thrombocytes. Leukemia can be defined as uncontrolled proliferation of abnormal types of blood cells, while the development of normal blood cells pauses. Failure to produce normal blood cells causes serious symptoms such as infection and bleeding. Bone marrow cancer patients, also known as leukemia, consult a doctor with symptoms such as anorexia, weight loss, fever, malnutrition, paleness, bleeding and bone pain. In addition, spleen, liver size, and enlarged lymph nodes can be observed. Lymph nodes, especially larger than 2 centimeters, should be investigated for reasons. For diagnosis, blood and marrow tissue samples should be taken and examined by bone marrow aspiration or biopsy methods. A simple blood count and examination of cells in the blood under a microscope can often be sufficient to make a diagnosis. However, definitive diagnosis is made by bone marrow examination. Leukemia treatment is done with chemotherapy drugs. Medicines may differ depending on the type of leukemia. The type, dosage and route of administration of the drugs to be used are determined by the attending physician. The duration of chemotherapy usually ranges from 6 months to 2 years. While bone marrow transplantation is the first option in the treatment of some leukemias, it is a treatment method that should be used in some leukemias only if the disease recurs. Successful results in the treatment of childhood leukemias are very high. The recovery rate, which was around 5% in the 1960s, varies according to the risk groups today, but it is around 90%. The success achieved in the treatment of leukemia in our country is at the level of modern countries with both chemotherapy and bone marrow transplantation.

What Should Be The Characteristics of the Stem Cell Transplant Center?

Various measures are taken in the Stem Cell Transplant Unit in order to prevent infections that can be transmitted to patients from the outside environment. These measures are;

  • At the entrance of each patient room, there is a special section between the room and the corridor, and it is ensured that both the transplant staff and the escorts are free from infections that may be carried from this section.
  • Bone marrow transplant patients are provided to use separate elevators.
  • There are special security measures that only allow authorized personnel to exit the floor where the Bone Marrow Transplant Unit is located.
  • Memorial Ankara Hospital Child Bone Marrow Transplant Unit has been designed in such a way that patients can comfortably pass this process.
  • The foods desired by the patients during the transplant are prepared under special conditions.
  • In order to protect them from infections, hepafilter systems that remove particles in the air are used throughout the transplant unit.

Which Stem Cell Transplant is Best for My Patient?

Stem cell transplantation consists of three stages: transplant, before and after transplantation. The basic requirement at any stage is the absolute cooperation between the transplant team and patient relatives. This cooperation strengthens with mutual trust principles. For this reason, any question should be directed to the posting team and there should be no room for question marks in mind. The procedures and treatments that need to be done during the transplant stages vary from patient to patient. The transplant team should inform patients and their relatives at every stage. The most correct treatment method and type of transplant (autologous or allogeneic), the source of stem cells to be used (bone marrow or peripheral stem cell or cord blood), the need for tissue compatibility (fully compatible intra-family donor or fully compatible non-relative donor or haploidentic transplant )). It should be kept in mind that every patient is special in itself and the transplant process should be carried out within this framework. Each member of the transplant team has the knowledge and equipment to successfully carry out this process.

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