Understanding the Disease

On this page:

Stem Cell Sources

Hematopoietic stem cells (HSC’s) are stem cells that develop into all the types of blood cells in the body. These include; white blood cells, red blood cells and platelets.

White blood cells (WBC): help fight and prevent infections
There are three very important types of WBC, essential to the proper functioning of the body’s immune system, which fight infection:

  • Neutrophils & Macrophages: fight fungal & bacterial infections by destroying germs
  • Lymphocytes: fight bacterial, viral and fungal infections. B lymphocytes make antibodies which help destroy germs in our body. T lymphocytes (T cells), attack viruses and other germs. In allogeneic transplants only, T cells from a bone marrow or stem cell donor can attack the recipient of a bone marrow or stem cell transplant and cause a reaction called Graft Versus Host Disease (GVHD). T cells from the recipient of a bone marrow transplant can also reject donor bone marrow cells and cause the graft to fail.

Red blood cells (RBC): carry oxygen to the body.

Platelets: help blood to clot in order to stop bleeding.

HSCs originate in the bone marrow, but are also present in peripheral blood or umbilical cord blood.

Bone Marrow
Bone marrow is a spongy material found inside bones. It is responsible for making marrow stem cells and other substances, which produce blood cells. Each type of blood cell has an important job.

Peripheral blood stem cells (PBSC): in addition to bone marrow that comes from inside bones, stem cells can also circulate in the veins and arteries of all people. These cells are known as peripheral blood stem cells (PBSC). Patients who are recovering from chemotherapy and normal individuals who are treated with certain drugs that stimulate the growth of the bone marrow have relatively large numbers of PBSC in their blood. The PBSC can be collected by a process called apheresis and used in certain situations as a source of stem cells for transplantations.

Umbilical Cord Blood (UCB): These are another source of stem cells that are found in the placenta and umbilical cord of a newborn baby after the cord has been cut. UCB has been successfully used as a source of bone marrow stem cells for transplantation in both related and unrelated patients.

Back to Top

What is a Bone Marrow or Stem Cell Transplant?

The goal of a bone marrow or stem cell transplant is to replace unhealthy or nonfunctioning bone marrow stem cells with normal healthy bone marrow stem cells.  The normal stem cells are taken from a donor.  The donor could be a brother or sister, parent, an unrelated individual or even the patient himself.  These stem cells are given to the patient following treatment with chemotherapy and sometimes radiation.  This treatment is called the conditioning regimen.

The timing and type of treatment depends on the disease being treated.  During the conditioning regimen, the transplant recipient or patient is treated with chemotherapy and/or radiation to prepare their body for the transplanted stem cells.  For children/adolescents with cancer, the purpose of the conditioning is to destroy any remaining cancer cells in the body.  For children with genetic diseases or marrow failure disorders, the purpose is to make room in the marrow for the donor stem cells to grow and to prevent the recipient from rejecting the donor marrow.

Following the conditioning, the transplant is performed.  This is accomplished by giving the donor’s marrow or stem cells to the patient the same way that a blood transfusion is given, that is, through an intravenous (IV) catheter or tube. The donor’s marrow or stem cells travel in the recipient’s bloodstream to the bone marrow space where they grow and mature over the next few weeks.

Back to Top

Types of Donors

When a child/adolescent is being considered for a bone marrow transplant (BMT), one of the first steps is to determine the best donor source for the stem cells needed for the procedure.

Allogeneic: a donor other than self
If an allogeneic transplant is indicated, the next step is to find out whether a family member is a suitable donor. This involves special blood studies called tissue typing performed on the blood from the patient and his/her family.

HLA typing: human leukocyte antigen is a fingerprint (or DNA) that represents our body’s ability to identify another person’s cells as foreign.
These tests help gauge how much the donor and recipient cells will recognize one another as the same or different. The greater the differences between the donor and recipient in the HLA typing, the greater the chance that the left over recipient immune system will reject the donor’s cells—resulting in rejection or graft failure, or that the donor immune cells will attack the recipient and cause a reaction called graft versus host disease (GVHD).

Each person inherits two sets of chromosomes, one set from their father and one set from their mother which makes up their tissue type. There is a 1 in 4, or 25% chance that any brother or sister will have inherited the same two sets of HLA genes as the patient. For a parent to be matched with his or her child, both parents must by chance have some HLA genes in common with each other. There is only a 1 in 200 chance that a parent and child will be HLA matched. The best donor is a histocompatible (HLA) matched relative who is usually a sibling or, in rare cases, a parent with an identical HLA tissue type. It is very unlikely for two unrelated individuals to have the same HLA genes in common; about 1 in a million chance. Fortunately the National Marrow Donor Program (NMDP) or its equivalent in your country if you do not live in the US has a very large computer registry, representing millions of donors from all over the world. This computer registry is used to find the best HLA unrelated match for patient’s without related donors.

  • Matched sibling donor (MSD): brother or sister (I think we should expand this a little as you did with the umbilical cord section. Perhaps discuss some advantages and disadvantages)
  • Matched related adult donor (MRD): parent or even more rarely another relative
  • Matched unrelated donor (MUD): unrelated individual whose stem cells match
    • NMDP: National Marrow Donor Registry (NMDP) When a related donor cannot be found and there is time to conduct a search, an alternative is to identify an unrelated donor, which is a healthy individual who is matched to the patient and is willing to donate bone marrow stem cells.
  • Unrelated Umbilical Cord blood (UCB): Cord blood, which is normally disposed of after a baby is born, contains a relatively large number of stem cells. There are over 30 cord blood registries worldwide which process and store cord blood collections from healthy babies. Potential advantages include; UCB does not need to be a perfect HLA match with the recipient and the units are readily available for transplantation. Disadvantages include the limited number of cells in the collection leading to a slower recovery of marrow function post transplant and potential graft rejection and no potential for a second infusion if one was needed.

Autologous:  patient is a donor for self
For some types of cancer, it is possible to use the patient’s own marrow stem cells either from the bone marrow or peripheral blood for the transplant.  This is called an autologous transplant.  This is used when there has been such an intense treatment of chemotherapy and/or irradiations used that the patient’s marrow function will recover too slowly to prevent very serious and life threatening infections. The autologous cells are used to “rescue” the marrow function. Some examples of types of cancers which might be treated using autologous stem cells include but are not limited to:

  • Brain Tumors
  • Neuroblastoma
  • Lymphomas
  • Sarcomas
  • Wilm’s Tumor
  • Germ Cell Tumor
  • Primitive neuroectodermal tumors (PNET)
  • Acute promyelocytic leukemia (APL)

Whenever possible, peripheral blood stem cells are used instead of bone marrow for autologous transplants.  Again, prior to admission for transplant, the patient’s stem cells are collected using a procedure called leukopheresis.  The procedure frequently requires the placement of a special intravenous line, called an apheresis catheter.  In preparation for the leukopheresis, the patient receives a drug called granulocyte colony stimulating factor (G-CSF), brand name Neupogen, for three to four days to stimulate stem cells to leave the bone marrow space and enter the blood stream.  During the stem cell collection or leukopheresis the patient’s blood is passed through a machine that collects the portion of white cells containing bone marrow stem cells.  The rest of the remaining white blood cells, red cells and platelets are given back to the patient.  Following the high dose chemotherapy, the stored stem cells are thawed and re-infused back into the patient.

If marrow needs to be harvested for transplant it is done several weeks to months before the transplant. The harvest is done in the operating room under general anesthesia and the stem cells are frozen in liquid nitrogen until the preparative therapy is completed, and the cells are needed to be re-infused for marrow recovery.

Advantages of an autologous transplant are that once stem cells are collected, they are readily available and there is an absence of the risk of graft versus host disease. Graft versus host disease (when the donor cells see the recipient as foreign and attack the host) is a side effect of allogeneic transplants only.   A potential disadvantage of an autologous bone marrow transplant is that there is a greater risk of relapse of the patient’s cancer.  Your physician will discuss which donor option is best for you and your child.

Back to Top

Who Needs a Bone Marrow Transplant?

There are a number of reasons for doing a bone marrow transplant.  The procedure can provide normal bone marrow to patients:

  • Whose own bone marrow stem cells are diseased, abnormal or defective
  • Whose own bone marrow has been destroyed by chemotherapy and radiation therapy in order to treat cancer
  • With genetic disease that affects all of the organs in the body

These three situations will be reviewed below in detail.

Back to Top

Stem Cell Defects

Some children are born with defects in bone marrow stem cells, while other children develop this later in life.  When one or a combination of these cells is abnormal it can result in fatal diseases such as:

  • Aplastic anemia
  • Thalassemia major
  • Sickle cell disease
  • Severe combined immunodeficiency disease (SCID)
  • Wiskott-Aldrich syndrome
  • Fanconi’s anemia
  • Chronic granulomatous disease

A transplant using healthy bone marrow stem cells from a donor is a potential cure for these diseases.

Back to Top

Cancer 

Bone marrow transplant can be used to treat many different types of cancers. Examples of some cancers which have been treated with bone marrow transplant include:

  • Leukemia
  • Lymphoma
  • Neuroblastoma
  • Brain Tumors
  • Sarcomas
  • Wilm’s Tumor
  • Germ Cell Tumor
  • Primitive neuroectodermal tumors (PNET)
  • Retinoblastoma

The treatment for these conditions uses high doses of chemotherapy and sometimes radiation therapy to kill all of the cancer cells in the body. However, this also kills the healthy bone marrow cells. Bone marrow stem cells for the transplant come from either a healthy related or unrelated donor or from the patient in some circumstances.

Back to Top

Genetic Diseases

Certain inherited diseases also may be treated with a bone marrow transplant. In some cases, only the marrow stem cells are affected, some examples would be:

  • Severe combined immunodeficiency disease (SCID)
  • Thalassemia major
  • Sickle cell disease

However, in many of the genetic disorders, there is a defect in the way chemicals are processed in the body that affects many organs including the heart, lungs, liver, kidneys, bones and usually the brain. Examples of these diseases are:

  • Hurler’s Syndrome
  • Alpha Mannosidosis
  • Osteopetrosis
  • Krabbe’s disease

With these conditions, the bone marrow cells may or may not be affected. The purpose of the bone marrow transplant for these diseases is to provide healthy cells from the donor that produce an enzyme needed to correct the chemical imbalance affecting many of the organs. For some genetic diseases, such as Hurler’s Syndrome a bone marrow transplant has been proven to be effective. For others, the benefit is not clear and further research needs to be done.

Back to Top

Medical Disclaimer

The information on the website is intended to introduce you to some of the medical procedures and treatments which you/your child may receive when undergoing a hematopoietic progenitor cell transplant. The information on the website provides general guidelines but cannot replace the recommendations of your primary medical team. Specific patient care treatment options and procedures are the prerogative of each patient and their medical care team. You are encouraged to discuss any concerns or questions you have with your medical care team. Although every attempt has been made to post information that is clear and accurate, no guarantee is made to the reliability, completeness, relevancy, accuracy, or timeliness of the content. No liability is assumed by the Pediatric Blood and Marrow Transplant Consortium for any damages resulting from use or access to information posted on this website.