Severe Combined Immunodeficiency (SCID) Treatment & Management

Updated: Aug 11, 2020
  • Author: Francisco J Hernandez-Ilizaliturri, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Treatment

Approach Considerations

Intravenous immunoglobulin (IVIG) replacement therapy may benefit patients with combined immunodeficiencies, such as severe combined immunodeficiency (SCID), X-linked immunodeficiency with hyper IgM syndrome (XHM), Good syndrome, and Wiskott-Aldrich syndrome (WAS). Appropriate supportive care, such as early identification of opportunistic infections or nutritional support, are necessary.

In WAS, other than prophylactic antibiotics and IVIG, splenectomy for thrombocytopenia and platelet transfusion in acute life-threatening bleeding can be used.

Note: Do not immunize these patients with live attenuated vaccines. Focus efforts on the treatment of infections, allergic reactions, and autoimmune and gastrointestinal diseases. Aggressive and prolonged antibiotic therapy covering Streptococcus pneumoniae and Haemophilus influenzae is indicated. Prophylactic antibiotic therapy has been recommended for patients with frequent infections. A course of metronidazole may result in dramatic improvement of the diarrhea and, to a certain extent, of malabsorption syndrome in these patients. Prophylactic antibiotic therapy may significantly decrease the incidence of infections.

Patients with adenosine deaminase (ADA) deficiency may benefit from adenosine deaminase enzyme replacement therapy with pegademase or elapegademase. The maximum effect on immunologic function does not occur for several months.

Allogeneic bone marrow or hematopoietic stem cell transplantation (HSCT) may be helpful for patients with SCID. Survival rates in these previously fatal conditions are around 90% in some case series.

This treatment strategy is highly successful when a human leukocyte antigen (HLA)–matched sibling donor is available; if such a donor is not available, however, few therapeutic options exist. Gene-modified, autologous bone marrow transplantation can circumvent the severe immunologic complications that occur when a related HLA-mismatched donor is used and thus represents an attractive alternative (see below). 

Allogeneic bone marrow transplantation has become the standard of care for certain patients with SCIDs (eg, X-linked severe combined immunodeficiency [XSCID], ADA deficiency). Patients with other immunodeficiency syndromes may benefit from bone marrow transplantation or HSCT, including those with WAS or XHM.

Many groups are exploring the potential benefits of HSCT based on alternative donors. Umbilical cord blood stem cell transplantation (UCBSCT) offers several advantages, including ready availability of the unit, a lower risk of transmitting viral diseases, no risk to the donor, and a lower risk of GVHD even in the absence of a perfect HLA match.

Another possibility for patients without a suitable sibling donor is a matched unrelated donor (MUD) HSCT. But in clinical practice, this therapy is limited due to high rates of graft versus host disease (GVHD) and transplant-related mortality.

Identification of a suitable MUD has been facilitated by recent advances, including the following: 

  1.  Continuous growth of volunteer donors worldwide
  2. High-resolution molecular techniques for HLA typing, which permits a better selection of donors
  3. Advances in critical care that have resulted in a significant decrease in MUD-HSCT transplant–related mortality and an increase in the survival of SCID infants who are severely infected at the time of diagnosis.

Early diagnosis before the development of permanent lung and liver damage and referral to a specialized center for bone marrow transplantation/HSCT are essential for therapeutic success.

Bertrand et al reported on a European experience with 178 patients in 18 centers who were treated with HLA, nonidentical, T-cell–depleted bone marrow transplantation. [23]  With a median follow-up of 57 months, disease-free survival was shown to be significantly better for patients with B-positive SCID (60%) than for patients with B-negative SCID (35%). [23]

Buckley et al found that the survival rate was not affected by the genetic type, but it was affected by race (ie, more white patients than black or Hispanic patients survived [P < 0.001]) and sex (all girls survived [P = 0.047]). [24]

Another report noted the inefficacy of bone marrow transplantation in correcting Job syndrome. [25]

Gene therapy

Despite the success that has been seen in some SCID patients treated with bone marrow transplantation, other patients experince failure to restore B-cell function or failure or rejection of the graft over time. A novel alternative strategy to circumvent graft failure/rejection is the use of gene transfer into autologous stem cells using retroviruses.

Gene therapy is a viable therapeutic option; advances in biotechnology have enabled the performance of this highly complex treatment for several immunodeficiency syndromes. [26, 27]

Cavazzana-Calvo et al published reports of the successful results of gene therapy for SCID-X1 disease in 2 children, opening new horizons for the future of these patients. [5]  This therapy resulted in complete immune reconstitution of the lymphoid system, with T-, B-, and NK-cell counts comparable to age-matched controls. [5]  An update on these 2 patients by the same authors and a report on 3 others confirmed the previous results.

Patients with ADA deficiency were the first to be enrolled in gene therapy trials. Since 2000, over 100  patients with ADA-SCID have been treated with gamma-retrovirus or lentivirus-mediated autologous hematopoietic stem cell gene therapy (HSC-GT), and the excellent safety and efficacy observed in these cases has established HSC-GT as an equal alternative to HSCT for these patients. [28]

In addition to ADA deficiency, , SCID-X1, WAS, RAG1 deficiency, and CD3 deficiency have been successfully treated with gene-modified autologous HSC-GT. In this technique, RNA viruses are the vectors most commonly used to introduce genetic information into hematopoietic stem cells and/or progenitor cells. It has been demonstrated that several T-cell precursors that carry a wild-type sequence of the disease-causing gene or a less harmful mutation can mature into functional mature T cells that provide adequate immunity. 

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Consultations

Consultations should be obtained with specialists from the following specialties:

  • Bone marrow transplantation
  • Gastroenterology
  • Nutrition
  • Infectious diseases
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Diet

In view of the presence of chronic diarrhea, patients often require enteral or parenteral supplementation.

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Activity

Physical activity should be encouraged. Patients may need isolation to decrease the risk of common viral and bacterial infections, such as avoiding crowded places. Strict hygienic practices are important.

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