Treatments for Severe Combined Immunodeficiency

Treatment

Hematopoietic (blood-forming) stem cell transplantation is the standard treatment for infants with SCID. Ideally, SCID infants receive stem cells from a sibling who is a close tissue match.

Source: NIAID (NIH)1

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Back to: « Severe Combined Immunodeficiency

Back to: « Combined Immunodeficiency

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Severe Combined Immunodeficiency (SCID) Treatment

Hematopoietic (blood-forming) stem cell transplantation is the standard treatment for infants with SCID. Ideally, SCID infants receive stem cells from a sibling who is a close tissue match. Transplants from matched siblings lead to the best restoration of immune function, but if a matched sibling is not available, infants may receive stem cells from a parent or an unrelated donor.

Source: NIAID (NIH)2

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What is the treatment for SCID?

Treatment for SCID may include the following:

  • Medications - especially antibiotic, antifungal, and antiviral medications to treat or prevent active infections.
  • Avoiding exposure to infections, especially ones that may be difficult to eradicate, such as chicken pox.
  • Use immunoglobulin supplementation (IVIg)
  • Blood and Marrow Transplantation - BMT provides patients with a functioning immune system that is capable of protecting them from infections. It can be a cure for SCID, and is highly effective in many patients, with best outcomes when an HLA-matched sibling donor is available, and if done early in life.
  • Enzyme replacement therapy - For patients with the type of SCID caused by deficiency of the enzyme Adenosine Deaminase (ADA), enzyme replacement therapy (with a medication known as PEG-ADA) may be used to enable immune cells to recover. This may allow patients more time to get to transplant with better immunity. In some instances, PEG-ADA may be used for years (without transplant) and be helpful in restoring immunity and preventing infections.
  • Gene therapy - Patients with some types of SCID have also undergone gene therapy to correct the genetic mutation in their immune cells. While this has been very successful in some patients there have been some serious complications and, at this point, gene therapy is still considered an investigational treatment option. There are ongoing clinical trials of gene therapy for ADA-SCID and X-SCID in the US and Europe using next generation vectors which appear to be more efficient and safer. There are plans for trials for RAG-SCID and Artemis-SCID in the next few years.

Source: RDCRN (NCATS/NIH)3

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What are the treatments for Leaky SCID?

In most cases, the treatments are similar to patients with classical SCID, and can include intravenous immunoglobulin, antibiotics, antifungals, specific treatments against the autoimmune complications (e.g. IVIg for autoimmune thrombocytopenia) and ultimately, blood and marrow transplantation.

Source: RDCRN (NCATS/NIH)4

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Why have medical professionals called Severe Combined Immunodeficiency Disease (SCID) a pediatric emergency?

SCID is a group of congenital disorders (disorders present at birth), in which affected infants fail to develop T-cells, a critical component of the immune system. As a result of severe infections, the condition can be fatal in infancy, unless treated with bone marrow transplantation, enzyme replacement therapy or gene therapy. SCID infants should be isolated from infections as soon as possible. Costs for treatment are usually lower if a child is diagnosed within the first 3 1/2 months of life before major infections develop. The diagnosis of SCID very early in life is a true pediatric emergency.

Source: RDCRN (NCATS/NIH)5

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Is there effective treatment for SCID?

The most effective treatment for SCID is transplantation of blood-forming stem cells from the bone marrow of a healthy person. Bone marrow stem cells can live for a long time by renewing themselves as needed and also can produce a continuous supply of healthy immune cells. A bone marrow transplant from a tissue-matched sister or brother offers the greatest chance for curing SCID.

However, most patients do not have a matched sibling donor, so transplants from a parent or unrelated matched donor are often performed. These latter types of transplant succeed less often than do transplants from a matched, related donor. All transplants done in the first three months of life have the highest success rate.

Source: NHGRI (NIH)6

Treatments for Severe Combined Immunodeficiency

Bone Marrow Transplant: Many patients with serious primary immune deficiencies such as SCID, WAS, or CGD require a Blood and Marrow Transplant (BMT) for cure of their disease. BMT is also known as a Hematopoietic Stem Cell Transplant (HSCT) and the terms BMT and HSCT are often used interchangeably.

BMT is a form of stem cell therapy and is life-saving for many infants and children with serious primary immune deficiencies. Bone marrow stem cells used for transplant come from another person (i.e. not the person with the primary immune deficiency). Stem cells will grow and form a new and normal immune system in the person affected by the primary immune deficiency.

Stem cells come from one of three sources:

(1) Bone Marrow - this is what is most commonly known as a “Bone Marrow Transplant”;

(2) Peripheral Blood (bone marrow stem cells found in the blood); or

(3) Umbilical cord from a newborn baby (contains a large number of bone marrow stem cells).

In general, the best stem cell donor is a sibling to the patient who is both (1) a match (also called an HLA-match, or human leukocyte antigen match), and (2) NOT affected by the same disease. For each sibling, these criteria only occur about 20% of the time. Your doctor will want to take blood from each sibling to determine if they would be a suitable donor.

If a sibling is not available or is not a suitable match, other possible donors may include (1) a parent or sibling who is not a match (sometimes called a “haploidentical” donor) (2) an unrelated person found on a stem cell registry, or (3) an unrelated umbilical cord blood donor. There are many factors that go in to deciding who the best donor is when a matched sibling is not available. Speak to your doctor about these decisions.

Your doctor may recommend that certain medications be given to your child before the stem cells are infused. This is referred to as a conditioning regimen and usually consists of various combinations of chemotherapy (drugs that open up space in the bone marrow to accept the new stem cells, and that suppress the patient’s immune system so that it does not reject the new stem cells) and possibly other immune suppressing medications. These drugs will usually be administered intravenously in the days or weeks before BMT. Many different conditioning regimens are available. Some forms of SCID may not require a conditioning regimen. There are many factors that go in to deciding a conditioning regimen. As a result, it is impossible to make general recommendations on this website about what is the best conditioning regimen, or whether a conditioning regimen is needed or not. Your doctor will be able to discuss with you the recommendations regarding the conditioning regimen.

One common question asked by patients and parents is, “How do the new stem cells get into the body?” The answer is, the stem cells go right into the blood stream! Stem cells do not need to be injected directly into the bone marrow with large needles. Patients do not need to be brought to an operating room for a major surgery to receive the stem cells. In fact, the stem cell infusion is actually a minor procedure, usually done in the patient’s hospital room. The procedure is in fact very similar to getting a blood transfusion. Patients will usually have a central line inserted before BMT. A surgeon or other doctor will insert the central line in a minor surgery. A central line is a type of longer intravenous line (of which there are various types in use) that goes in through the skin (often on the chest, but they can be other places) and ends in the large veins inside the chest. The stem cells are infused through the central line and into the blood stream. The infusion takes anywhere between 15 minutes and 4 hours, depending upon the type of product and the volume. Once in the blood stream, the stem cells eventually “home” to the bone marrow (which is continuous with the blood) - where they will make new blood and a new immune system over time for the patient.

BMT can be a difficult process for patients and their families. Patients need to be treated at specialized hospitals that are used to treating young infants and children with primary immune deficiencies (many of these hospitals are members of the PIDTC). Patients and their families may need to be away from their home for months at a time. Patients may spend weeks or months in a hospital after the transplant. Patients can become very sick - both before the transplant and after. Infections are a major problem for BMT patients, particularly those with primary immune deficiencies. Please see the section on “What are the complications of Blood and Marrow Transplant?” for further information. Follow up occurs for years after BMT and probably will be life-long.

Source: RDCRN (NCATS/NIH)7

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Gene Therapy: PID Treatment

What is gene therapy?

In its current available form, Gene Therapy (GT) is an experimental therapy that aims to replace the defective gene with a copy of the healthy gene. This allows the cell to start producing normal protein in hopes of curing the disease. Scientists have found that one of the most efficient ways to introduce the corrected gene into the cell is to use modified viruses. Scientists first inactivate the virus so that it cannot produce disease and then "load" it with the "normal gene"(for example, the WASP Gene in the case of WAS). These "loaded" viruses, referred to as "vectors", are then used to introduce the normal gene into the patient.

Because gene therapy is experimental, it only occurs at a few hospitals in the world. Patients are required to be enrolled on a research study to receive this treatment. Your doctor can help you in determining if you / your child are eligible for a research study. All research studies, including those involving gene therapy, are required to be registered before they begin on a publicly accessible website.

The most common website is ClinicalTrials.gov. You can go to this website and search the name of your / your child’s condition along with gene therapy to see what trials may be available.

Gene therapy trials for Wiskott-Aldrich Syndrome, Chronic Granulomatous Disease, ADA SCID and XSCID are ongoing.

What happens during GT?

The following are the four basic steps of gene therapy.

  1. The vector is prepared and loaded with the normal gene, in preparation for introduction into the patient.
  2. Doctors collect blood-forming stem cells from the patient's bone marrow or the blood. These cells are then grown in large numbers outside the body. Next, these cells are mixed with the vector. The virus infects these cells, converting them to repaired cells.
  3. The patient is then given chemotherapy, in preparation for GT. This helps make space in the marrow for the repaired cells to multiply and to make sure that the patient’s body does not reject the repaired cells.
  4. The repaired cells are now introduced into the patient in a process similar to blood transfusion.

These repaired cells then continue to multiply, forming more numbers of normal cells. Over time, the repaired cells should produce enough to cure the patient.

Source: RDCRN (NCATS/NIH)8

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Enzyme replacement therapy: One particular kind of SCID, called adenosine deaminase deficiency (ADA)-SCID, is caused by lack of an enzyme (a protein in the body that helps break down other chemicals).

ADA-SCID is the only type of SCID where patients can receive enzyme replacement.

Source: RDCRN (NCATS/NIH)9

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References

  1. Source: NIAID (NIH): niaid.nih.gov/ diseases-conditions/ severe-combined-immunodeficiency-scid
  2. Source: NIAID (NIH): niaid.nih.gov/ diseases-conditions/ scid-treatment
  3. Source: RDCRN (NCATS/NIH): rarediseasesnetwork.org/ cms/ pidtc/ Learn-More/ Disorder-Definitions
  4. ibid.
  5. ibid.
  6. Source: NHGRI (NIH): genome.gov/ 13014325/ learning-about-severe-combined-immunodeficiency-scid/ 
  7. Source: RDCRN (NCATS/NIH): rarediseasesnetwork.org/ cms/ pidtc/ Learn-More/ Therapies/ BMT
  8. Source: RDCRN (NCATS/NIH): rarediseasesnetwork.org/ cms/ pidtc/ Learn-More/ Therapies/ Gene-Therapy
  9. ibid.

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Note: This site is for informational purposes only and is not medical advice. See your doctor or other qualified medical professional for all your medical needs.