About Pediatric Stem Cell and Bone Marrow Transplants

Overview of Pediatric Stem Cell Transplants and Cellular Therapy

A pediatric stem cell transplant is a medical procedure used to treat children with certain diseases. It involves replacing a child's damaged or diseased stem cells with healthy ones. Stem cells are immature cells found in either the bone marrow (bone marrow transplant), peripheral blood (peripheral blood stem cell transplant), or cord blood (cord blood transplant) that develop into red blood cells, white blood cells, and platelets. Cellular therapies include the use of modified cells to fight specific types of cancer (CAR-T cells). 

There are two main types of pediatric stem cell transplants: 

  • Autologous transplant: In this type of transplant, the child's own stem cells are collected, stored, and then reintroduced into their body after they have received high-dose chemotherapy. This treatment destroys the diseased cells but also damages the stem cells. The reintroduced stem cells help the body to produce new, healthy blood cells. 
  • Allogeneic transplant: In this type of transplant, stem cells are collected from a matched donor, such as a sibling, a mismatched related donor, an unrelated donor, or umbilical cord blood. After completion of chemotherapy +/- radiation, the donor's stem cells are then infused into the child's bloodstream. The new stem cells travel to the bone marrow and begin to produce healthy blood cells. 

Pediatric stem cell transplants are used to treat a variety of conditions, including: 

  • Cancers, such as leukemia, lymphoma and neuroblastoma 
  • Blood disorders, such as aplastic anemia and sickle cell disease 
  • Inherited immune system disorders, such as severe combined immunodeficiency (SCID)

What are Stems Cells?  

Hematopoietic stem cells are basically the body's master cells of the bone marrow and immune system. They are special human cells found in the bone marrow that have two important properties: 

  • Self-renewal: Stem cells can divide and copy themselves for long periods. This helps replenish the pool of stem cells in the body. 
  • Differentiation: In general, stem cells are unspecialized, meaning they haven't yet matured into a specific type of cell, like a muscle cell or a brain cell. Hematopoietic stem cells have the amazing ability to develop into many different blood and immune cell types. This is like having a blank slate that can become a variety of specialized blood and immune cells. 

What is Bone Marrow?  

Bone marrow is the soft, spongy tissue found inside the center of most of your bones. It contains hematopoietic stem cells which are considered the factory of your blood cells because it's responsible for producing red blood cells, white blood cells, and platelets. These cells are all essential for various functions in your body. 

  • Red blood cells carry oxygen throughout your body. 
  • White blood cells fight infection. 
  • Platelets help blood clot to stop bleeding. 

There are two main types of bone marrow: 

  • Red bone marrow: This is the active type of bone marrow that produces most of your blood cells. It's found in the center of your flat bones, such as your ribs, breastbone, pelvis, and skull, and in the ends of your long bones. 
  • Yellow bone marrow: This type of bone marrow is mostly fat and stores energy. It can convert back to red bone marrow if your body needs to produce more blood cells. Yellow bone marrow is found in the center of your long bones, such as your arms and legs. 

How does Cellular Therapy Work?  

Cellular therapy is a developing field that utilizes the power of cells to treat various diseases. It works in a few different ways, depending on the type of cell therapy and the condition being targeted: 

  • Replacing Damaged Cells: This approach is often used with stem cells. Stem cells, due to their self-renewal and differentiation abilities, can be introduced into the body to replace diseased or damaged cells. For instance, in bone marrow transplants for leukemia, stem cells from a donor or the patient themselves are used to repopulate the bone marrow and restore healthy blood cell production. 
  • Supporting and Repairing Tissues: Some cell therapies involve introducing cells that secrete beneficial factors or promote tissue repair. Mesenchymal stem cells, found in adult tissues like bone marrow, are a type often used in this way. They may not directly differentiate into new tissues but can release molecules that encourage healing and reduce inflammation. 
  • Engineering Immune Cells to Fight Disease: This exciting area of cellular therapy, called CAR-T cell therapy, involves taking a patient's immune T cells, modifying them in a lab to recognize and attack cancer cells, and then reintroducing them into the patient. These engineered T cells can then target and destroy cancer cells more effectively. 

Here's a simplified breakdown of the general cellular therapy process: 

  • Cell Collection: Cells for therapies can be a patient's own (autologous) or from a matched donor (allogeneic). Stem cells might be extracted from bone marrow or blood, while immune cells for CAR-T are collected only from blood. 
  • Cell Processing: Depending on the therapy, the collected cells might undergo processing in a lab. This could involve expansion (growing more cells), genetic modification (for CAR-T therapy or for transplant in patients with abnormal hemoglobin including sickle cell disease and thalassemia), or other manipulations. 
  • Delivery: The processed cells are then delivered back into the patient's body. This can be through intravenous infusion, injection, or application to a specific area. 

Types of Stem Cell Transplantation

There are two main categories of stem cell transplants differentiated by the origin of the transplanted stem cells. 

Autologous Transplant

In this type, a patient's own stem cells are used. Doctors collect stem cells from the patient's blood or bone marrow before they undergo high-dose chemotherapy  for conditions like cancer. After the treatment destroys cancerous cells, the collected stem cells are reintroduced back into the patient's body. These healthy stem cells help rebuild the immune system and resume production of healthy blood cells. A patient’s own cells can also be collected for processing to become CAR-T cells, or gene therapies for patients with sickle cell disease and beta-thalassemia.  

Allogenic Transplant

This type uses stem cells from a matched or mismatched donor. The donor can be: 

  • Related donor: This is often a sibling with a close genetic match to the patient. 
  • Unrelated donor: If a suitable sibling match isn't available, doctors search national or international registries for an unrelated donor with compatible human leukocyte antigen (HLA) markers. 
  • Umbilical cord blood: Stem cells can also be collected and stored from umbilical cord blood after childbirth. This option might be used when a perfect HLA match is difficult to find with adult donors. 

Reduced-Intensity Stem Cell Transplantation

Reduced-intensity transplants use lower doses of chemotherapy and/or radiation. This makes the transplant less toxic and easier to tolerate, but it also means that it may not be as effective in killing cancer cells. 

Reduced-intensity transplants may be a good option for patients undergoing transplant for immune deficiency, or who are not healthy enough for a standard transplant.

Criteria: Who is a Candidate?

Determining who is a good candidate for stem cell transplantation is a complex decision made by a team of specialists. Here are some general factors they consider: 

Patient's Health

Overall health status: Candidates are evaluated comprehensively to identify any other health problems that  could complicate the transplant process.

Disease Characteristics

Type of Disease

Stem cell transplants are most commonly used for blood cancers like leukemia, lymphoma and some blood disorders like aplastic anemia, or immune system disorders. 

Disease Stage 

The stage and severity of the disease play a role. Transplants in children with leukemia and lymphoma are often used when other treatments haven't been successful, or the disease has relapsed. It is usually better to perform a transplant when none of the leukemia or lymphoma can be detected (in remission).  

Donor Availability and Compatibility

Finding a suitable stem cell donor is crucial for allogeneic transplants. This depends on the availability of a well-matched donor, either a sibling, unrelated donor, or umbilical cord blood. Advances in these transplants also allow for a parent to be a suitable donor for their child (haploidentical stem cell transplant). 

Human Leukocyte Antigen (HLA) Compatibility

These genetic markers determine how well the recipient's body accepts the donor's stem cells; HLA disparities also lead to potential complications after the transplant.  

Other Factors

Supportive Care Network

The transplant process can be lengthy and demanding. Having a strong support system to help the patient through recovery is important.

These are general guidelines. The decision of whether a patient is a candidate for a stem cell transplant will be made on an individual basis by a team Lurie Children’s team of specialists who consider all the specific details of the patient's case. 

Preparing for Transplantation

Preparing for a stem cell transplant involves several steps to optimize the procedure's success and your well-being, such as medical assessments, pre-transplant condition and emotional and practical considerations. Click here for details on the Stem Cell Transplantation Timeline

Side Effects

Stem cell transplants can have a variety of side effects, stemming from two main causes: 

  • The conditioning treatment: This refers to the high-dose chemotherapy and/or radiation therapy used before the transplant to destroy cancerous cells or suppress the immune system.
  • The transplant itself: The introduction of new stem cells can sometimes lead to complications. 

Here's a breakdown of some potential side effects: 

Short-Term Side Effects (Common) 

  • Nausea and vomiting caused by chemotherapy & radiation 
  • Mouth sores and taste changes 
  • Fatigue 
  • Hair loss 
  • Low blood cell counts: This can lead to increased risk of infection, bleeding, anemia (lack of red blood cells), and thrombocytopenia. You may need blood transfusions to manage these conditions.
  • Diarrhea 

Here are some additional points to consider: 

  • The severity and duration of side effects can vary depending on the type of transplant, underlying disease for which the transplant is done, and your overall health. 
  • Your Lurie Children’s team will closely monitor you for side effects and provide supportive care to manage them. 

Potential Complications 

Stem cell transplants are complex procedures with the potential for serious complications. While many side effects are common and manageable, certain complications can be life-threatening. Here's a closer look at some potential complications: 

  • Graft versus Host Disease (GVHD): This is a potential problem for patients undergoing  allogeneic transplants where the donor's immune system attacks the recipient's body. It can be:
    • Acute GVHD: Occurs early on in the transplant process, with symptoms like rash, fever, nausea, diarrhea, and rise of bilirubin.
    • Chronic GVHD: Develops later (months or even years) and can affect multiple organs like skin, eyes, mouth, lungs, liver, and gastrointestinal tract.
  • Infections: Due to suppressed immunity, transplant recipients are highly susceptible to infections, especially during the initial recovery period when new blood cell production hasn't fully resumed. Bacterial, viral, and fungal infections can all be serious complications.
  • Graft failure: This occurs when the transplanted stem cells don't engraft or take hold in the recipient's bone marrow. This can lead to treatment failure and the need for a second transplant.
  • Organ damage: The high-dose chemotherapy and radiation therapy used in conditioning can damage organs like the lungs, heart, kidneys, and liver, leading to long-term health problems.
  • Secondary cancers: There's a slightly increased risk of developing new cancers, particularly leukemia, after the transplant due to the conditioning treatments.
  • Pulmonary complications: Lung problems like inflammation or infections can occur due to conditioning treatments or the transplant itself.
  • Vascular occlusion: This is a blockage of blood vessels, which can be a serious complication, especially in the liver.

Your Lurie Children’s team can help mitigate or treat many of these conditions. 

Outlook

The long-term outlook for stem cell transplant patients depends on several factors, including:

  • The underlying disease: The type of cancer or blood disorder being treated significantly impacts the prognosis. Some diseases have a higher cure rate with transplants than others. 
  • Type of transplant: Autologous transplants (using your own stem cells) generally have a lower risk of complications compared to allogeneic transplants (using donor stem cells). 
  • Success of the transplant: Factors like engraftment (successful take hold of new stem cells) and occurrence of complications like GVHD influence long-term survival.

Here's a general overview of the long-term outlook for stem cell transplant recipients:

Potential Benefits

  • Cure: For some diseases, stem cell transplants can be curative, meaning the cancer or blood disorder goes into remission and doesn't return. 
  • Long-term disease control: Even if not curative, transplants can sometimes lead to long-term disease control, allowing patients to live for many years with a manageable condition.

Long-Term Considerations

  • Follow-up care: Regular checkups and monitoring are crucial for long-term management. This may involve blood tests, imaging scans, and checking for signs of GVHD or secondary cancers. 
  • Late effects: Some patients experience late effects from the transplant or conditioning treatments years later. Their Lurie Children’s care team will ensure continuity of care once the patient ages out of the pediatric hospital. 
  • Maintaining a healthy lifestyle: Following a healthy diet, exercising regularly, and avoiding smoking are essential for overall well-being and reducing the risk of long-term complications. 

Survival Rates

It's difficult to provide specific survival rates as they vary depending on multiple factors. However, according to the National Cancer Institute, 70-80% of patients who survive the first two years after a stem cell transplant for leukemia or lymphoma can expect to live for many more years. 


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