Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 21 peer-reviewed journal articles Updated
Immunology

Curative Treatments: Transplant and Gene Therapy

At a Glance

Severe Combined Immunodeficiency (SCID) requires urgent treatment to build a functioning immune system. Primary cures include stem cell transplants from a healthy donor or gene therapy using the baby's modified cells. Receiving treatment before 3.5 months of age offers the highest survival rates.

Because SCID is a life-threatening emergency, the goal is to provide a “new” immune system as quickly and safely as possible [1][2]. Today, there are two primary ways to cure SCID: replacing the baby’s immune cells with a donor’s cells (HSCT) or “fixing” the baby’s own cells (Gene Therapy) [3][4].

Hematopoietic Stem Cell Transplant (HSCT)

Commonly known as a bone marrow transplant, this is the “gold standard” treatment for most types of SCID [3][5]. Doctors take healthy stem cells from a donor and infuse them into your baby’s bloodstream. These cells then travel to the bone marrow and begin “printing” new, healthy immune cells [3].

Finding a Match

The success of a transplant often depends on how closely the donor’s “tissue type” (HLA) matches the baby’s [6].

  • Matched Sibling Donor (MSD): This is the best-case scenario. A brother or sister who is a perfect HLA match offers the highest success rates [6][7].
  • Matched Unrelated Donor (MUD): If a sibling isn’t a match, doctors search international registries for a volunteer who matches the baby [6].
  • Haploidentical (Half-Match): Usually a parent. While only a 50% match, modern techniques can “clean” these cells to make them safe and effective for the baby [6][8].

Understanding “Conditioning”

Before the new cells are given, your baby may receive conditioning, which is typically a course of chemotherapy [9].

  • Why it’s used: Conditioning “makes room” in the bone marrow for the new cells to grow and helps prevent the baby’s body from rejecting them [9][10].
  • Balancing Act: Doctors tailor the intensity of chemotherapy (Full vs. Reduced Intensity) based on the baby’s specific SCID subtype and their current health, aiming to ensure long-term immune recovery while minimizing side effects like organ toxicity or future fertility issues [9][11].

Gene Therapy: Fixing the Original Cells

For some types of SCID (specifically ADA-SCID and X-linked SCID), gene therapy is a newer curative option [12][4].

  • How it works: Doctors take the baby’s own stem cells, use a modified, harmless virus to “insert” a healthy copy of the missing gene into those cells, and then return them to the baby [13][14].
  • Major Advantage: Since the cells belong to the baby, there is zero risk of Graft-versus-Host Disease (GVHD)—a common transplant complication where donor cells “attack” the patient’s body [15][12].

The “Bridge” for ADA-SCID: PEG-ADA

If your baby has the ADA subtype, they have a unique third option called Enzyme Replacement Therapy (ERT), using a medication like PEG-ADA (Revcovi) [16][17].

  • Stabilization: This is an injection given once or twice a week that replaces the missing enzyme. It helps “wake up” the immune system and detoxify the body [18][19].
  • The Bridge: PEG-ADA is usually not a permanent cure, but it “buys time” to keep the baby healthy and infection-free until they can undergo a transplant or gene therapy [16][17].

Timing is Everything

Regardless of the treatment chosen, the most important factor for success is timing. Babies who receive their curative treatment early—ideally before 3.5 months of age and before they develop any major infections—have survival rates as high as 90% or more [1][20][21].

To prepare for this major step, read the Building Your Care Team page.

Common questions in this guide

What are the curative treatments for SCID?
The most common curative treatment for SCID is a hematopoietic stem cell transplant, often called a bone marrow transplant. For specific types like ADA-SCID or X-linked SCID, gene therapy may also be a curative option.
What is conditioning before a stem cell transplant?
Conditioning is a course of chemotherapy given before a transplant. It helps make room in the bone marrow for new, healthy cells to grow and prevents the baby's body from rejecting the donor cells.
What is the difference between a stem cell transplant and gene therapy for SCID?
A stem cell transplant replaces the baby's immune cells with healthy cells from a donor. Gene therapy uses the baby's own stem cells, fixing the missing gene in a lab before returning them, which eliminates the risk of graft-versus-host disease.
What is PEG-ADA used for in babies with SCID?
PEG-ADA is an enzyme replacement therapy specifically for babies with ADA-SCID. It acts as a temporary bridge to keep the baby healthy and infection-free until they can undergo a permanent transplant or gene therapy.
When should a baby with SCID receive treatment?
Timing is critical for SCID treatments. The highest success rates are seen when babies receive curative treatments before three and a half months of age and before any major infections occur.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Which donor type do you recommend for my child, and why?
  2. 2.What kind of conditioning (chemotherapy) will my baby need, and what are the short-term and long-term risks?
  3. 3.Is my baby a candidate for gene therapy instead of a donor transplant?
  4. 4.If we are starting enzyme replacement therapy (PEG-ADA), how long will my baby stay on it before a permanent treatment?
  5. 5.How will you monitor for Graft-versus-Host Disease (GVHD) after the transplant?
  6. 6.What is the expected timeline from the start of conditioning to when we can take our baby home?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (21)
  1. 1

    Survival After Hematopoietic Stem Cell Transplantation in Severe Combined Immunodeficiency (SCID): A Worldwide Review of the Prognostic Variables.

    Goebel GA, de Assis CS, Cunha LAO, et al.

    Clinical reviews in allergy & immunology 2024; (66(2)):192-209 doi:10.1007/s12016-024-08993-5.

    PMID: 38689103
  2. 2

    Outcome of hematopoietic stem cell transplantation for severe combined immunodeficiency and impact of newborn screening on overall survival: A single referral center study.

    Anchoo C, Lev A, Simon AJ, et al.

    The Journal of allergy and clinical immunology 2025; (155(6)):1800-1812 doi:10.1016/j.jaci.2025.01.029.

    PMID: 39900265
  3. 3

    Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India.

    Aluri J, Desai M, Gupta M, et al.

    Frontiers in immunology 2019; (10()):23 doi:10.3389/fimmu.2019.00023.

    PMID: 30778343
  4. 4

    Advances in gene therapy for inborn errors of immunity.

    Ott de Bruin LM, Lankester AC, Staal FJT

    Current opinion in allergy and clinical immunology 2023; (23(6)):467-477 doi:10.1097/ACI.0000000000000952.

    PMID: 37846903
  5. 5

    Severe Combined Immunodeficiency Disorders.

    Chinn IK, Shearer WT

    Immunology and allergy clinics of North America 2015; (35(4)):671-94.

    PMID: 26454313
  6. 6

    Approaches to the removal of T-lymphocytes to minimize graft-versus-host disease in patients with primary immunodeficiencies who do not have a matched sibling donor.

    Slatter MA, Gennery AR

    Current opinion in allergy and clinical immunology 2017; (17(6)):414-420 doi:10.1097/ACI.0000000000000402.

    PMID: 28968273
  7. 7

    Recent advances in treatment of severe primary immunodeficiencies.

    Gennery A

    F1000Research 2015; (4()).

    PMID: 26918153
  8. 8

    [HLA- haploidentical donor hematopoietic transplantation for severe aplastic anemia achieved comparable outcomes with HLA- unrelated donor transplantation].

    Lu Y, Wu T, Cao X, et al.

    Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 2016; (37(1)):35-8 doi:10.3760/cma.j.issn.0253-2727.2016.01.007.

    PMID: 26876251
  9. 9

    Long Term Outcome and Immune Function After Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency.

    Gennery AR, Lankester A,

    Frontiers in pediatrics 2019; (7()):381 doi:10.3389/fped.2019.00381.

    PMID: 31616648
  10. 10

    Long-Term Health Outcome and Quality of Life Post-HSCT for IL7Rα-, Artemis-, RAG1- and RAG2-Deficient Severe Combined Immunodeficiency: a Single Center Report.

    Abd Hamid IJ, Slatter MA, McKendrick F, et al.

    Journal of clinical immunology 2018; (38(6)):727-732 doi:10.1007/s10875-018-0540-9.

    PMID: 30105620
  11. 11

    Posttransplant complications in patients with marrow failure syndromes: are we improving long-term outcomes?

    Hudda Z, Myers KC

    Hematology. American Society of Hematology. Education Program 2023; (2023(1)):141-148 doi:10.1182/hematology.2023000471.

    PMID: 38066882
  12. 12

    Gene therapy outpaces haplo for SCID-X1.

    Kohn DB

    Blood 2015; (125(23)):3521-2 doi:10.1182/blood-2015-04-641720.

    PMID: 26045591
  13. 13

    Long-Term Safety and Efficacy of Gene Therapy for Adenosine Deaminase Deficiency.

    Booth C, Masiuk K, Vazouras K, et al.

    The New England journal of medicine 2025; (393(15)):1486-1497 doi:10.1056/NEJMoa2502754.

    PMID: 41092330
  14. 14

    Preclinical ex vivo IL2RG gene therapy using autologous hematopoietic stem cells as an effective and safe treatment for X-linked severe combined immunodeficiency disease.

    Hu M, Xu Q, Zhang F, et al.

    Genes & diseases 2025; (12(3)):101445 doi:10.1016/j.gendis.2024.101445.

    PMID: 40092492
  15. 15

    Review of Cutaneous Graft-vs-Host Disease.

    Ballester-Sánchez R, Navarro-Mira M, Sanz-Caballer J, Botella-Estrada R

    Actas dermo-sifiliograficas 2016; (107(3)):183-93.

    PMID: 26626500
  16. 16

    Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency.

    Kohn DB, Hershfield MS, Puck JM, et al.

    The Journal of allergy and clinical immunology 2019; (143(3)):852-863 doi:10.1016/j.jaci.2018.08.024.

    PMID: 30194989
  17. 17

    Adenosine Deaminase (ADA)-Deficient Severe Combined Immune Deficiency (SCID): Molecular Pathogenesis and Clinical Manifestations.

    Bradford KL, Moretti FA, Carbonaro-Sarracino DA, et al.

    Journal of clinical immunology 2017; (37(7)):626-637 doi:10.1007/s10875-017-0433-3.

    PMID: 28842866
  18. 18

    Treatment with Elapegademase Restores Immunity in Infants with Adenosine Deaminase Deficient Severe Combined Immunodeficiency.

    Hicks ED, Hall G, Hershfield MS, et al.

    Journal of clinical immunology 2024; (44(5)):107 doi:10.1007/s10875-024-01710-z.

    PMID: 38676811
  19. 19

    Long-Term Immune Reconstitution in ADA-Deficient Patients Treated With Elapegademase: A Real-World Experience.

    Murguia-Favela L, Suresh S, Wright NAM, et al.

    The journal of allergy and clinical immunology. In practice 2023; (11(6)):1725-1733 doi:10.1016/j.jaip.2023.01.028.

    PMID: 36736953
  20. 20

    SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery.

    Haddad E, Logan BR, Griffith LM, et al.

    Blood 2018; (132(17)):1737-1749 doi:10.1182/blood-2018-03-840702.

    PMID: 30154114
  21. 21

    Clinical Features and HSCT Outcome for SCID in Turkey.

    Ikinciogullari A, Cagdas D, Dogu F, et al.

    Journal of clinical immunology 2019; (39(3)):316-323 doi:10.1007/s10875-019-00610-x.

    PMID: 30924026

This page explains severe combined immunodeficiency (SCID) treatments for educational purposes. Always consult your pediatric immunologist and transplant team for specific medical guidance regarding your baby's care.

Get notified when new evidence is published on Severe combined immunodeficiency.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.