Hematopoietc Cell Transplant

• • Hematopoietic Cell Transplant

    • Currently, a Hematopoietic Cell Transplant (HCT) is the only proven curative treatment available for Wiskott-Aldrich Syndrome.  The cells in the bone marrow (stem cells) are abnormal in patients with WAS and need to be replaced with healthy, donor stem cells in order to to cure the disease.  The process by which these abnormal cells in the patient are replaced with healthy donor cells is referred to as a HCT or transplant.  On this site, the word "transplant" and HCT are used interchangeably.  During a transplant for WAS, at least three major things happen:

  • The patients blood forming stem cells are destroyed using medicines.  This helps to make place for the donor cells in the marrow.  It also destroys the patients immune system, allowing the patient's body to accept the donor cells.

  • The donor cells are given to the patient.

  • The donor cells grow and multiply, curing the patient.

Stem cells can be obtained from three different sources: 

• • The bone marrow of the donor.

  • Small numbers of stem cells exit from the bone marrow and are found in the blood and are called peripheral blood stem cells (PBSC). These cells can be stimulated to move to the peripheral blood in large numbers so that they can be harvested from the blood of the donor.

  • Cord blood, which is the blood that is collected from the placenta and the umbilical cord after the baby is born, is a rich source of stem cells.

The Transplant Process

Once a patient is identified to be eligible for a transplant, the best possible donor is identified for him.  The patient's body is more likely to accept cells that are from a donor that are most similar to his own cells (just as a patient  with O+ blood type accepts blood transfusions from another patient who is O+, but will destroy all others). A patient's immune system identifies and destroys cells that are not from his own body as "foreign".   Therefore, the donor is selected very carefully to minimize the two types of negative reactions: Graft Rejection and Graft versus Host Disease (GvHD).  Graft rejection occurs when the donor cells are not accepted by the body of the patient.  The opposite reaction is called Graft Versus Host Disease. GvHD occurs when the donors white blood cells view the patient’s body as foreign and attack the patients organs. 

The process by which the best possible donor is obtained is called HLA matching. The donors could be one of the following three people:

• Matched Sibling Donor (MSD):  They are perfectly matched donors and the best possible donors.  Each sibling has a 25% chance of being a perfect match.  Occasionally other family members may be perfect matches.

• Matched Unrelated Donor (MUD):  If a matched sibling is not available, then a search is made of databases around the world for the best possible match. In most, but not all cases, acceptable donors are found for every patient. This is the second choice for donors in patients with WAS.  

• MisMatched Related Donor (MMRD):  If no match is found and the patient needs to have a transplant, then one of the parents or other relatives may be selected as donors.  They partially match the patients HLA type and are not the ideal donors for transplant.   There are times however, when they are the best available match for the patient.

Pre Transplant Evaluation:  Once the best donor is identified the pre-transplant evaluation begins.  During the pre-transplant evaluation several tests are done to evaluate the function of the kidneys, heart, lungs etc to determine that the patient will be able to withstand the rigors of the transplant process and to have a baseline recording for further evaluation.  Financial planning is done at this point and measures are set in place for the emotional support of the parents during the process.  Going through a  transplant is challenging and emotionally exhausting.  Having a local support group through family, friends and religious affiliations can help to ease the process.  The hospital transplant team will be there to guide you through the process physically and emotionally. Once all the evaluations and support systems are in place, the patient is hospitalized for the transplant. 

In the Hospital:  Most often the patient is hospitalized the day before the medications are started.  Some children may have to be hospitalized earlier to get them ready for the transplant. Several medications are given while the child is in the hospital and lab work is done frequently, up to every day at times.  To prevent the child from having numerous pokes every day, sturdier, temporary IV lines (referred to as a Broviac or a Hickman Catheter) are implanted in a vein in the child's chest. 

Medications (chemotherapy) are then given to destroy the patient’s blood forming cells and to make place in the bone marrow for the donor cells.  These medications help to destroy the patient’s immune system so that it does not reject the donor cells. The process is called myeloablation or conditioning. Commonly used chemotherapy drugs for transplant are given over 8 days.  For this reason the day that chemotherapy is started is referred to as Day -9.  Chemotherapy is continued until day -1.  This is a "rest day" when no chemotherapy is given.  On Day "0" the donor cells are infused into the patient.  The donor cells are infused into the blood in a simple process similar to a regular blood transfusion.  The days after this are counted up as day +1, +2 etc. 

Blood samples are taken very frequently, even every day, to check for normal functioning of the body and to check if the donor cells are growing.  Due to the chemotherapy, the patient will have a lower number of red blood cells, white blood cells and platelets in the blood. Over time the donor cells will grow and make new blood cells.  This is called "engraftment" and is an important milestone in the transplant journey.  "Engraftment" usually happens between Day +10 to Day + 28. Until such time that the donor cells grow and make enough cells, the patients are given transfusions of red blood cells and platelets as needed.  IVIG is given as a replacement on a regular basis, until such time that the donor's white blood cells are functioning well.

During this process, the patients are on several different medications.  Medications may be given to prevent the donor cells from attacking the patients organs (GvHD). Because the patients have no immune system until the donor cells are well established, they are highly prone to infections.  Antibiotics, antivirals and antifungals are given for the prevention of infection and aggressive treatments are started if the patient develops a fever. Visitors are restricted to reduce the exposure to potential infections.  To decrease the chance of infection, patients are put in rooms with special air filters.  They may also be in a room with a positive pressure air system to make sure that the air from the outside does not enter the room.  These methods to reduce infection are referred to as "protective or reverse isolation".  It is important to follow the reverse isolation procedures outlined by the BMT team hospital scrupulously as infections can be serious and cause significant setbacks in the transplant path.      

After Discharge:  Patients are usually in the hospital for 25-45 days, until after engraftment happens and the doctors determine that they are ready to be discharged.  Until 100 days have passed after the transplant, if possible patients stay within a 20 minute reach of the hospital in case an emergency were to arise.  During this time labs are done very frequently, up to everyday.  After the 100 day milestone, patients may be able to return to their homes, if all is stable.  Labs and visits to the hospital are done on a weekly basis until the blood counts have stabilized and their immune system is better.  Because they are at high risk for infections, patients movement outside the home is restricted and visitors to the home are limited.  With all going well, patients have a normally functioning immune system (full immune reconstitution) by 2 years after transplant and can lead a normal life.  These numbers are just averages and it may vary significantly from patient to patient, depending on the circumstances and the complications that may arise.

Transplant Data

The first successful bone marrow transplant  for WAS took place in 1968.   Significant advances in the field of HCT in the last two decades has improved the success rate for transplants. 5 year survivals for children transplanted under the age of 5 years with a perfect sibling match approaches 90%.   When the transplant is done at experienced centers, a closely matched unrelated transplant is almost as successful as a MSD transplant1 in patients under 5.  However, the management of MUD transplants in children is significantly more complicated2 and prolonged than an MSD. 

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The long term outcome following BMT was studied by Ozsahin et al in 20083.  An analysis of significant events was done on 96 WAS patients who received transplants between 1979 and 2001 who survived at least 2 years following transplant.  Significant events include chronic graft-versus-host disease (cGVHD), autoimmunity, infections, and pre and post transplant complications.

The 7-year EFS was significantly influenced by donor group:

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