Since the 1960's until recently a Hematopoietic Stem Cell Transplant (HSCT) was the only proven curative treatment available for Wiskott-Aldrich Syndrome.  With the approval of ex vivo lentiviral gene therapy (Waskyra), in December of 2025, gene therapy (GT) is an option for patients who do not have a sibling donor or a well matched donor, and for patients for whom HSCT could be risky.  

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 HSCT, HCT, are used interchangeably.  During a transplant for WAS, at least three major things happen:

• • Medications referred to as chemotherapy are given to destroy the patient’s blood forming cells and to make place in the bone marrow for the donor cells. It also destroys the patients immune system, allowing the patient's body to accept the donor cells.

  • The donor cells are infused into 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.  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.  While making the decision to use a perfectly matched sibling, it is important to check matched female siblings to see if they are a carrier for WAS.  Recent study has shown that not all carrriers are healthy and some may manifest signs of WAS.  it is important to check the carrier sibling to ensure that they are healthy before proceeding to be a donor.  Many centers do not use carriers as donors.  

• 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. As each parent shares half of their DNA with their child, each parent is a potential "half-match" for their child and are referred to as haplo identical donors.  In the last decade, significant progress has been made in the field of haplo-idential transplantaion and the results of such transplants are comparable in terms of mortality.  While they are not the first choice as donors, such transplants are becoming more common due to the ease of access to the donor (parent is almost always available) and the cost savings associated.  Similar to a carrier sibling donor as described above, it is important to check the mother if she is a carrier.  If she is a carrier, a center may prefer to use the father, or may have the carrier mother undergo further evaluation to ensure that she can be a healthy donor.  

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 chemotherapy is started.  Some patients 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 patient's chest. 

Chemotherapy is 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 may be 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.
Overall Survival and Event Free Survival and contributory factors: According to the most recent studies, the 5 overall survival (OS) for patients undergoing transplant between 1990-2028 was 87% and the event free survival was 78%¹ . Events were defined as death from any cause, second HCT, stem cell boost (non-conditioned stem cell infusion), donor lymphocyte infusion (DLI; excluding planned infusions), or chimerism <5% in whole blood, myeloid or T cells.  A similar study done in more recent transplants (2006-2017) showed that the overall 3 year survival was 89%²  The factors a

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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