Strimvelis (Autologous CD34+ ADA Gene Therapy)
One-time ex vivo gene therapy for children with ADA-SCID
Quick Facts About Strimvelis
Key Takeaways About Strimvelis
- One-time, potentially curative: A single intravenous infusion of the child's own gene-corrected stem cells can restore a functional immune system for life
- Only for ADA-SCID without a matched donor: Strimvelis is specifically indicated for children with ADA-deficient SCID who have no suitable HLA-matched related hematopoietic stem cell donor
- Single designated treatment center: Strimvelis must be prepared fresh and is administered exclusively at San Raffaele Hospital in Milan, Italy — the product cannot be shipped
- Long-term monitoring required: Children must be followed for at least 15 years to detect rare but serious risks such as leukemia or autoimmune disease
- Busulfan conditioning: Low-dose busulfan chemotherapy is given before the infusion to make space in the bone marrow for the new stem cells, which itself has side effects
What Is Strimvelis and What Is It Used For?
Strimvelis is a one-time ex vivo autologous gene therapy used to treat children with adenosine deaminase severe combined immunodeficiency (ADA-SCID) who do not have a matched related hematopoietic stem cell donor available. It works by correcting the underlying genetic defect in the child's own blood stem cells and returning them to the body to build a functional immune system.
Strimvelis represents a landmark in the history of medicine: it was the first ex vivo stem cell gene therapy to receive a full marketing authorization from the European Medicines Agency (EMA), granted in 2016. Rather than giving a conventional drug or relying on a donor transplant, Strimvelis treats the root genetic cause of ADA-SCID by delivering a healthy copy of the defective gene directly into the child's own blood-forming stem cells.
The active substance of Strimvelis is a population of autologous CD34+ enriched cells — the patient's own hematopoietic (blood-forming) stem and progenitor cells — that have been transduced outside the body with a gammaretroviral vector encoding the human adenosine deaminase (ADA) complementary DNA. Because the cells come from the child themselves (“autologous”), there is no risk of graft rejection and no risk of graft-versus-host disease (GvHD), which are the main complications of conventional donor stem cell transplantation.
Understanding ADA-SCID
Adenosine deaminase severe combined immunodeficiency (ADA-SCID) is an extremely rare inherited disease, affecting roughly 1 in 200,000 to 1 in 1,000,000 newborns worldwide. It is caused by mutations in the ADA gene, which codes for the enzyme adenosine deaminase. Without this enzyme, toxic purine metabolites such as deoxyadenosine triphosphate (dATP) accumulate inside developing lymphocytes, poisoning them before they can mature. The result is a near-complete absence of T-cells, B-cells and natural killer (NK) cells — the “soldiers” of the immune system.
Children born with ADA-SCID appear healthy at birth but develop life-threatening infections in the first weeks and months of life. Without effective treatment, most do not survive beyond early childhood. Historically, ADA-SCID was one of the forms of SCID described as “bubble boy disease” because affected children needed to live in protective isolation. Today, newborn screening programs in many countries allow earlier detection, giving families a crucial window to access curative therapies such as Strimvelis or hematopoietic stem cell transplantation.
How Strimvelis Works
The therapeutic goal of Strimvelis is to provide the child with a permanent source of ADA-producing blood cells. Hematopoietic stem cells are collected from the child's bone marrow (or, if mobilized beforehand, from the peripheral blood). In a specialized laboratory, these CD34+ cells are exposed to a replication-deficient gammaretroviral vector that permanently integrates a functional copy of the human ADA gene into the cells' DNA. The modified cells are then purified, tested and formulated for infusion.
After the child receives a short course of lymphodepleting chemotherapy with busulfan to make room in the bone marrow, the gene-corrected cells are infused through a vein. They home back to the bone marrow, engraft, and begin producing all the different types of blood cells — including functional T-cells, B-cells and NK-cells that now contain the corrected ADA gene. Over weeks and months, the child's immune system is gradually reconstituted.
Long-term follow-up data, including more than two decades of experience at San Raffaele Hospital in Milan, show that Strimvelis can provide durable engraftment and sustained immune reconstitution in the majority of treated children. Many patients are able to come off enzyme replacement therapy (PEG-ADA), leave protective isolation and lead essentially normal childhoods.
Strimvelis is not a conventional medicine — each dose is individually manufactured from a single patient's own cells, administered only once in a lifetime, and prepared fresh at the designated treatment center. It cannot be “shipped” like a pharmaceutical product, and it cannot be given at local hospitals. Families must travel to the qualified treatment center for both cell collection and infusion.
What Should You Know Before Taking Strimvelis?
Before Strimvelis is given, the treatment center conducts a thorough assessment of the child's overall health, organ function, infection status and genetic diagnosis. Strimvelis must not be given if the child is hypersensitive to any of its components or to busulfan, or if there are pre-existing conditions that rule out safe conditioning chemotherapy. Enzyme replacement therapy must be stopped in advance.
Strimvelis is a powerful one-time treatment that requires meticulous patient selection and preparation. Decisions are made by a multidisciplinary team including pediatric immunologists, transplant physicians, geneticists and pharmacists. Parents and legal guardians receive detailed counseling about the expected benefits, the known and theoretical risks, and the intensive follow-up required for many years after the infusion.
Contraindications
Strimvelis must not be administered if:
- The patient is hypersensitive (allergic) to any of the active or inactive ingredients listed in the product information
- The patient has a history of allergy to bovine serum albumin, which is used during the manufacturing process
- There are known contraindications to the busulfan conditioning regimen, such as severe active infection, decompensated organ failure, or prior radiation to the pelvis or abdomen that would significantly increase conditioning toxicity
- The patient has a confirmed diagnosis of a myeloid malignancy or myelodysplasia prior to treatment
- The patient tests positive for replication-competent retrovirus on pre-screening
Warnings and Precautions
The specialist team will discuss the following risks in detail before treatment begins:
- Insertional oncogenesis: The retroviral vector integrates into the genome and, in theory, could activate a nearby gene involved in cancer. No cases of leukemia have been reported in Strimvelis-treated patients to date, but lifelong monitoring is required because similar earlier-generation gammaretroviral vectors were linked to leukemia in other SCID trials
- Autoimmune disorders: Autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, autoimmune hepatitis and Guillain-Barre syndrome have been reported after Strimvelis. Most cases respond to immunosuppressive treatment
- Neutropenia and infection: White blood cell counts drop after the busulfan conditioning and remain low until the new cells engraft. Severe infections, including life-threatening bacterial, viral and fungal infections, can occur during this period
- Busulfan-related toxicity: Low-dose busulfan can cause mucositis, liver toxicity, veno-occlusive disease, transient seizures, hair loss and, importantly, partial or complete infertility in later life
- Incomplete immune reconstitution: A minority of patients experience delayed or partial recovery of B-cell or NK-cell function, which may require immunoglobulin replacement therapy or, in rare cases, a subsequent allogeneic stem cell transplant
- Manufacturing failure: In rare cases, it may not be possible to manufacture a dose that meets release criteria from a specific patient's cells. In such cases the treatment cannot proceed
- Viral reactivation: Latent viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus or varicella zoster may reactivate during the period of immune recovery
Children treated with Strimvelis must be enrolled in a structured long-term follow-up program for a minimum of 15 years. This program tracks immune reconstitution, retroviral vector integration sites, autoimmune signs, fertility outcomes and any signs of hematologic malignancy. Families commit to regular scheduled visits with the specialist team.
Tests and Monitoring Before Treatment
A comprehensive pre-treatment evaluation typically includes:
- Confirmation of ADA-SCID diagnosis by enzyme assay and ADA gene sequencing
- HLA typing of the patient and all first-degree relatives to confirm that no matched related donor is available
- Screening for active or latent infections: HIV, hepatitis B and C, CMV, EBV, HTLV, toxoplasma, syphilis and tuberculosis
- Assessment of heart, lung, liver and kidney function
- Complete blood count, coagulation profile and immunoglobulin levels
- Baseline imaging as clinically indicated (chest X-ray, abdominal ultrasound)
- Assessment of ability to tolerate general anesthesia for bone marrow harvest
Stopping Enzyme Replacement Therapy
Most children with ADA-SCID are receiving enzyme replacement therapy with pegademase bovine (PEG-ADA) at the time of referral. PEG-ADA must be discontinued at least 10 to 15 days before Strimvelis infusion so that circulating ADA enzyme does not interfere with engraftment or mask whether the gene-corrected cells are producing their own enzyme. This washout period requires close supervision and may temporarily increase infection risk.
Pregnancy, Breastfeeding and Fertility
Strimvelis is indicated for pediatric patients, so pregnancy and breastfeeding are generally not applicable at the time of treatment. However, the busulfan conditioning regimen can cause partial or complete infertility in adulthood in both boys and girls. Where feasible, options such as pre-treatment fertility preservation (for example, cryopreservation of ovarian tissue or testicular tissue in older children) should be discussed with the family, although these options are limited in very young children.
Patients who have received Strimvelis must never donate blood, organs, tissues or cells for transplantation. This is because Strimvelis contains genetically modified cells that should not be transferred to another person.
Driving and Operating Machinery
Strimvelis is given to young children, so direct driving-related concerns usually do not apply to the patient. However, parents should be aware that fatigue, neurological symptoms during the immediate recovery period and busulfan-related transient effects can limit normal activities for weeks to months. The specialist team will advise when it is safe to resume school, sports and other activities.
How Does Strimvelis Interact with Other Drugs?
The most clinically important interactions involve enzyme replacement therapy (PEG-ADA), which must be stopped before Strimvelis, busulfan as conditioning chemotherapy, and live vaccines, which are contraindicated during the immune recovery period. Any immunosuppressive or cytotoxic medication must be reviewed by the transplant team.
Because Strimvelis works by replacing the child's own hematopoietic stem cells with genetically corrected versions, any medication that affects bone marrow function, immune development or the engraftment environment can alter its safety and effectiveness. Parents must inform the treatment center of every medicine, supplement and herbal product the child is taking before and after the infusion.
Major Interactions
| Interacting Drug/Class | Effect | Recommendation |
|---|---|---|
| Pegademase bovine (PEG-ADA) | Circulating enzyme may mask or interfere with engraftment and assessment of gene-corrected cell function | Discontinue at least 10–15 days before Strimvelis infusion |
| Busulfan | Required conditioning agent, but narrow therapeutic window and risk of hepatic, neurologic and gonadal toxicity | Given at low dose (“non-myeloablative”) by specialist team with pharmacokinetic monitoring |
| Live attenuated vaccines | Serious, potentially fatal infection in an immunocompromised child | Contraindicated until full immune reconstitution is documented, typically at least 1–2 years after infusion |
| Other immunosuppressants (corticosteroids, calcineurin inhibitors) | May delay immune reconstitution and increase infection risk | Avoid unless required for a specific indication; dose and duration decided by transplant team |
| Granulocyte colony-stimulating factor (G-CSF) | May be used before harvest to mobilize CD34+ cells; not routinely used after Strimvelis | Decided by specialist team; not a standard part of post-infusion care |
| Phenytoin, phenobarbital, itraconazole | Alter busulfan metabolism and systemic exposure | Avoid or adjust dosing under specialist guidance during the conditioning period |
| Myelosuppressive drugs (azathioprine, mycophenolate, cytotoxic agents) | Suppress engraftment of gene-corrected cells | Avoid in the peri-infusion period unless medically unavoidable |
| Intravenous immunoglobulin (IVIG) | Used to prevent or treat infections during immune reconstitution; does not interfere with gene-corrected cells | Can be continued or started as clinically needed to bridge incomplete immunity |
Vaccination Considerations
Vaccinations require careful timing and planning around Strimvelis. General principles include:
- Live attenuated vaccines (BCG, oral polio, rotavirus, MMR, varicella, yellow fever) must not be given before full immune reconstitution is documented. A child with ADA-SCID should never have received live vaccines before diagnosis; the team will confirm vaccination history carefully
- Inactivated vaccines may be given once the immune system has recovered sufficiently to mount a response. Routine vaccination schedules are typically restarted 1–2 years after Strimvelis, based on specific immune markers
- Seasonal influenza vaccination (inactivated) is often recommended for the patient and household contacts as soon as it is considered safe
- Household contacts should avoid live oral polio vaccine and should inform their doctors of the patient's status; most other live vaccines are acceptable for household members with standard precautions
Many children continue to need regular intravenous or subcutaneous immunoglobulin (IVIG/SCIG) for months to years after Strimvelis until their own B-cell function recovers fully. This is expected and does not indicate that gene therapy has failed.
What Is the Correct Dosage of Strimvelis?
Strimvelis is given as a single intravenous infusion containing a minimum of 4 million CD34+ cells per kilogram of body weight (4 × 10⁶ cells/kg). The exact cell number is individualized based on the patient's weight and the yield of the manufacturing process. The dose is given only once in a lifetime.
Strimvelis is not a conventional medication with a daily, weekly or cyclical dosing schedule. Instead, the “dose” is the total number of autologous gene-corrected CD34+ stem cells that the child receives on a single day. The process from referral to infusion typically takes several weeks and is coordinated entirely by the qualified treatment center.
Step 1: Cell Collection (Bone Marrow Harvest)
Bone Marrow Harvest Procedure
The child is given general anesthesia in a specialized operating theater. Bone marrow is aspirated from the posterior iliac crests (hip bones) using multiple fine needle punctures. The volume harvested is calculated based on body weight and the target CD34+ cell yield. Alternatively, if clinically appropriate, peripheral blood stem cell collection after G-CSF mobilization may be considered. The procedure is usually completed within 1 to 2 hours.
Step 2: Manufacturing
Ex Vivo Gene Correction
In the on-site clean room facility, CD34+ stem and progenitor cells are selected from the bone marrow using immunomagnetic beads. The purified cells are cultured for a short time in the presence of growth factors and then exposed to the retroviral vector carrying the ADA gene. Transduced cells are washed, tested for sterility, viability and potency, and formulated in an infusion bag. Manufacturing and release testing take approximately 3 days.
Step 3: Busulfan Conditioning
Non-Myeloablative Conditioning
In the days before the Strimvelis infusion, the child receives a short course of low-dose intravenous busulfan (typically divided doses over 2 days) to partially clear existing bone marrow cells and create space for the gene-corrected cells to engraft. Plasma busulfan concentrations are monitored to individualize the regimen and reduce toxicity. Supportive medications (anti-seizure prophylaxis, anti-nausea therapy, infection prophylaxis) are administered in parallel.
Step 4: Strimvelis Infusion
Target Dose: Minimum 4 × 106 autologous CD34+ cells per kg body weight
On the day of infusion, the freshly prepared cell dispersion is delivered from the clean room to the patient's bedside. After identity verification and premedication (typically an antihistamine and paracetamol/acetaminophen to reduce infusion-reaction risk), Strimvelis is infused through a central venous catheter over approximately 20 minutes. The total volume and number of bags depends on the individual product. The infusion must be completed within 6 hours of release because the product cannot be frozen or stored.
Adults
Strimvelis is not indicated in adults. Clinical data are restricted to pediatric patients with ADA-SCID. Adults with ADA deficiency are typically managed with enzyme replacement therapy or, in rare cases, allogeneic hematopoietic stem cell transplantation.
Children
The recommended dose for eligible children is a minimum of 4 × 106 CD34+ cells per kilogram of body weight, delivered as a single intravenous infusion. The majority of treated patients historically have been infants and young children up to around 6 years of age. Age is not a strict cut-off; decisions are based on disease severity, general health, availability of a donor and ability to tolerate the conditioning regimen.
Elderly
Strimvelis is not relevant to the elderly population because ADA-SCID presents in early infancy and virtually never goes undiagnosed into adulthood. There are no dosing recommendations for elderly patients.
Renal or Hepatic Impairment
No formal dose adjustment studies of Strimvelis have been conducted in renal or hepatic impairment, as these conditions are rare in infants with ADA-SCID and are not considered contraindications per se. The transplant team will individualize the busulfan conditioning regimen based on organ function assessment.
After Infusion: Monitoring
After the infusion, the child typically remains hospitalized for several weeks until blood counts recover and the risk of early infection subsides. Key monitoring includes:
- Daily blood counts, electrolytes, and liver/kidney function
- Regular checks for infection (blood cultures, viral PCR for CMV, EBV and adenovirus)
- Lymphocyte subset analysis to track immune reconstitution
- Measurement of ADA enzyme activity in red blood cells to confirm gene correction
- Vector copy number analysis to confirm engraftment of gene-corrected cells
- Long-term monitoring for leukemia, autoimmune disease and growth/development
Missed Doses and Re-Treatment
Strimvelis is a one-time treatment. If the product fails to engraft adequately, options may include a second manufacturing attempt from stored cells, restarting enzyme replacement therapy or proceeding to an allogeneic (donor) hematopoietic stem cell transplant. These decisions are made jointly by the treatment team and the family.
Overdose
Because the dose is strictly defined by the child's body weight and the cell count manufactured, “overdose” in the pharmaceutical sense is not clinically relevant. The infusion protocol, clean-room release criteria and bedside verification are designed to prevent administration of a miscalculated dose.
What Are the Side Effects of Strimvelis?
Common side effects include fever, prolonged low blood counts, rash, respiratory infections, elevated liver enzymes and reactions related to busulfan conditioning. Serious risks include autoimmune disorders, severe infections during the recovery period and a theoretical risk of leukemia due to retroviral vector integration. Any new symptom after infusion should be reported immediately.
Strimvelis is a powerful one-time treatment, and many of the adverse effects reflect the combined impact of the bone marrow harvest, busulfan conditioning chemotherapy and subsequent immune reconstitution. The specialist team is trained to recognize and manage these complications early. Frequencies below are based on clinical trial experience and long-term registry data.
Contact the treatment team or go to the nearest emergency department immediately if the child experiences high fever, chills, severe bleeding or bruising, jaundice (yellowing of the skin or eyes), dark urine, sudden weakness on one side of the body, seizures, severe pain or any signs of serious infection after Strimvelis. Early recognition of complications such as autoimmune hepatitis, sepsis or cytopenias is essential.
Side Effects by Frequency
Very Common (affects more than 1 in 10 patients)
- Fever (pyrexia): often occurs during the conditioning period and during immune reconstitution
- Neutropenia and other cytopenias: temporary low counts of white blood cells, red blood cells and platelets while the gene-corrected cells engraft
- Anemia: fatigue, pallor, shortness of breath due to low red blood cell count
- Upper respiratory tract infections: runny nose, cough, sore throat
- Rash and eczema: skin reactions during and after immune recovery
- Elevated liver enzymes (ALT/AST): transient hepatic involvement related to busulfan or immune reconstitution
- Hypertension: elevated blood pressure, sometimes linked to steroid use or fluid balance
- Stomatitis and mucositis: painful inflammation of the mouth and gut lining caused by busulfan
- Nausea, vomiting, diarrhea: conditioning chemotherapy side effects
- Alopecia: temporary hair loss due to busulfan
- Hypogammaglobulinemia: low antibody levels during B-cell recovery
Common (affects up to 1 in 10 patients)
- Autoimmune hemolytic anemia (AIHA): antibodies attack the patient's own red blood cells, causing fatigue, jaundice and anemia
- Autoimmune thrombocytopenic purpura (ITP): low platelets with easy bruising or bleeding
- Cytomegalovirus (CMV) reactivation or infection
- Epstein-Barr virus (EBV) reactivation
- Pneumonia and other lower respiratory infections
- Allergic reactions: including infusion-related hypersensitivity to DMSO or bovine serum albumin
- Growth and developmental delays: usually transient and related to the underlying disease and conditioning
- Atopic dermatitis flares
- Hypothyroidism and other endocrine disturbances
Uncommon (affects up to 1 in 100 patients)
- Autoimmune hepatitis: inflammation of the liver caused by the immune system, presenting with jaundice and elevated liver enzymes
- Guillain-Barre syndrome: autoimmune attack on peripheral nerves causing weakness and sensory changes
- Hepatic veno-occlusive disease / sinusoidal obstruction syndrome: a serious complication of busulfan conditioning
- Bone marrow dysfunction: prolonged cytopenias that do not resolve within the expected timeframe
- Severe infections (sepsis, invasive fungal disease)
- Seizures related to busulfan or electrolyte disturbances
Rare / Theoretical (affects up to 1 in 1,000 patients or based on known class risks)
- Insertional oncogenesis (leukemia or myelodysplasia): integration of the retroviral vector close to a proto-oncogene could in principle trigger a leukemic clone. No cases have been reported in Strimvelis patients to date, but the risk is the reason for lifelong monitoring
- Replication-competent retrovirus: theoretical risk of formation of a replicating virus from the vector; extensive release testing is performed to exclude this possibility
- Secondary malignancies unrelated to the vector (for example, skin cancers in later life)
- Infertility: busulfan-associated impaired fertility may not be apparent until adolescence or adulthood
Busulfan Conditioning Toxicity
A large fraction of the “side effects” of Strimvelis in the first weeks are in fact attributable to the low-dose busulfan conditioning regimen rather than to the gene-modified cells themselves. Busulfan is a cytotoxic agent that temporarily depletes bone marrow and mucosal cells. Typical manifestations include mucositis, nausea and vomiting, temporary hair loss, elevated liver enzymes and prolonged low blood counts. Pharmacokinetic monitoring of busulfan levels is performed routinely to individualize the dose and minimize toxicity.
Autoimmune Complications
A characteristic feature of ADA-SCID and its treatments is an increased risk of autoimmune disease during and after immune reconstitution. This is thought to reflect an imbalance between newly formed regulatory and effector lymphocytes. Autoimmune hemolytic anemia and autoimmune thrombocytopenia are the most frequent manifestations; autoimmune hepatitis and Guillain-Barre syndrome have also been reported. Most cases respond to steroids, intravenous immunoglobulin or rituximab under specialist care.
Long-Term Safety Monitoring
Because Strimvelis uses a gammaretroviral vector that integrates into the patient's genome, the EMA requires enrollment in a long-term follow-up registry for at least 15 years. Follow-up visits monitor blood counts, immune reconstitution, ADA enzyme activity, autoimmune markers, fertility outcomes and vector integration sites. Early detection of a potential problem allows rapid intervention.
How Should You Store Strimvelis?
Strimvelis is a fresh, living cellular product that cannot be frozen or stored long-term. It is prepared and administered on the same day at the designated qualified treatment center. The infusion must start within 6 hours of release by the quality control laboratory. Patients and families are not responsible for storage.
Unlike conventional medicines, Strimvelis is not supplied in pharmacies and is not available for take-home use. It is a living cell therapy that must remain metabolically active and sterile until it reaches the patient's bloodstream. Strict handling requirements are built into every step of the treatment pathway.
Strimvelis is stored at a controlled room temperature of approximately 15–30°C in its infusion bag between release and administration and must not be refrigerated or frozen. Cooling or freezing would destroy the stem cells and render the product useless. Once quality-control release testing is completed, the product must be infused within six hours; if this window is missed, the infusion cannot proceed.
The infusion bag must be inspected by the administering healthcare professional before use. Any sign of damage, leakage, discoloration or aggregation is an absolute reason not to infuse the product. The patient's identity is verified against the product label at multiple checkpoints, because Strimvelis is autologous and must never be given to any person other than the patient from whom the cells were collected.
Strimvelis is never dispensed to the patient or family for home use. All preparation, storage and administration occur at the designated treatment center, where trained staff handle the product in a dedicated clean-room facility under good manufacturing practice (GMP) conditions. Families do not need to do anything to store or prepare the product.
What Does Strimvelis Contain?
Strimvelis contains the patient's own genetically modified CD34+ hematopoietic stem cells suspended in an infusion medium. The formulation also includes sodium chloride, human serum albumin and residual components from the manufacturing process such as bovine serum albumin. Each dose is individually manufactured and contains a minimum of 4 × 10⁶ CD34+ cells per kg body weight.
The active ingredient of Strimvelis is an autologous CD34+ enriched cell fraction transduced ex vivo with a replication-deficient gammaretroviral vector encoding the human adenosine deaminase (ADA) complementary DNA. In practical terms, this means hematopoietic stem and progenitor cells from the child's own bone marrow that now carry a permanent, working copy of the ADA gene.
Excipients (Inactive Ingredients)
The infusion formulation contains the following inactive components, used to maintain the viability and sterility of the cell product:
- Sodium chloride (physiological saline base)
- Human serum albumin (stabilizer)
- Residual bovine serum albumin from the culture medium
- Residual growth factors used during ex vivo transduction
- Residual vector components and cell culture medium traces
- No DMSO or other cryoprotectants, because Strimvelis is not frozen
Important Composition Notes
Because Strimvelis is a genetically modified living cell product, patients, families and healthcare professionals should be aware of the following:
- Autologous: each dose is unique to one patient and must never be administered to any other person
- Sodium content: the overall sodium load is low and is not usually a clinical concern, but infants with cardiac or renal conditions will have fluid balance monitored carefully
- Bovine serum albumin residue: patients with known beef allergy or hypersensitivity to bovine proteins should be identified before treatment
- Gammaretroviral vector: integrates into the patient's genome; the vector itself is replication-defective and cannot produce new virus
Appearance and Packaging
Strimvelis is a translucent, colorless to slightly yellow cell dispersion supplied in a transfer bag containing approximately 50 mL of product. The bag is clearly labeled with patient identifiers, cell count, lot number, release date and expiry time. The bag is enclosed in protective overwrap for transport from the clean-room facility to the patient bedside within the same hospital.
Frequently Asked Questions About Strimvelis
Strimvelis is a one-time ex vivo autologous gene therapy used to treat children with adenosine deaminase severe combined immunodeficiency (ADA-SCID), a rare inherited disorder in which the immune system cannot develop normally. It is used specifically for patients who do not have a suitable human leukocyte antigen (HLA)-matched related hematopoietic stem cell donor. A healthy copy of the ADA gene is inserted into the child's own blood stem cells using a retroviral vector, and these corrected cells are then infused back into the body to rebuild a functional immune system.
Strimvelis is given as a single intravenous infusion of the patient's own gene-corrected CD34+ hematopoietic stem cells. Before the infusion, the child receives low-dose busulfan chemotherapy as conditioning to make space in the bone marrow for the new cells, and any enzyme replacement therapy with PEG-ADA is stopped at least 10–15 days in advance. Strimvelis is only administered at one designated qualified treatment center in Europe (San Raffaele Hospital in Milan, Italy), because the product must be prepared fresh and infused within hours of release.
The most serious risks include a theoretical risk of leukemia or myelodysplasia due to retroviral vector integration (insertional oncogenesis), serious autoimmune disorders such as autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, autoimmune hepatitis or Guillain-Barre syndrome, severe infections during the period of immune reconstitution, and toxic effects of the busulfan conditioning regimen, including liver toxicity, prolonged cytopenias and potential later infertility. Children treated with Strimvelis are monitored for a minimum of 15 years under a structured follow-up program.
Strimvelis is approved for pediatric patients with a confirmed diagnosis of ADA-SCID who do not have a suitable HLA-matched related hematopoietic stem cell donor. Additional eligibility criteria include adequate general health to tolerate bone marrow harvest and busulfan conditioning, no contraindications to busulfan, sufficient CD34+ cell yield to manufacture a valid dose, and no pre-existing myeloid malignancy. Final treatment decisions are made by a multidisciplinary team of pediatric immunologists and transplant specialists at the designated treatment center.
Long-term follow-up of children treated at the designated center shows that Strimvelis can provide durable immune reconstitution and survival in the majority of patients, and many are able to come off enzyme replacement therapy and leave protective isolation for good. For this reason, it is often described as potentially curative. However, a minority of patients have incomplete immune recovery and may need ongoing immunoglobulin replacement, partial re-initiation of enzyme replacement, or in rare cases a subsequent allogeneic stem cell transplant. Lifelong specialist follow-up is essential.
Strimvelis is a fresh, living cell product that is never frozen and cannot be stored long-term. It is prepared in the clean-room facility of the qualified treatment center and must be infused within 6 hours of release by the quality-control laboratory. The infusion bag is kept at controlled room temperature (approximately 15–30°C) and must never be refrigerated. All handling and administration are performed by trained hospital staff; patients and families are never responsible for storage.
In the months after Strimvelis, while the new immune system is rebuilding, most children continue to receive antimicrobial prophylaxis (to prevent Pneumocystis pneumonia and other infections) and regular intravenous or subcutaneous immunoglobulin replacement. These are gradually withdrawn as the child's own immune markers normalize. In the long term, the majority of children no longer need enzyme replacement therapy (PEG-ADA), although a minority require partial or temporary reinitiation. Your specialist team will tailor the follow-up plan to your child's individual response.
References
- European Medicines Agency (EMA). Strimvelis — Summary of Product Characteristics and European Public Assessment Report. Available at: ema.europa.eu/en/medicines/human/EPAR/strimvelis. Accessed January 2026.
- Aiuti A, Roncarolo MG, Naldini L. Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products. EMBO Mol Med. 2017;9(6):737-740. doi:10.15252/emmm.201707573
- Cicalese MP, Ferrua F, Castagnaro L, et al. Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency. Blood. 2016;128(1):45-54. doi:10.1182/blood-2016-01-688226
- Kohn DB, Booth C, Kang EM, et al. Lentiviral gene therapy for X-linked chronic granulomatous disease. Nat Med. 2020;26(2):200-206. (Context for vector safety profile.)
- European Society for Immunodeficiencies (ESID). Registry and clinical care recommendations for severe combined immunodeficiency (SCID). Updated 2025.
- Primary Immunodeficiency Treatment Consortium (PIDTC). Natural history and outcome studies of SCID. J Allergy Clin Immunol. Multiple volumes.
- Gaspar HB, Cooray S, Gilmour KC, et al. Long-term persistence of a polyclonal T-cell repertoire after gene therapy for X-linked severe combined immunodeficiency. Sci Transl Med. 2011;3(97):97ra79.
- World Health Organization (WHO). International Classification of Diseases, 11th Revision (ICD-11). Severe combined immunodeficiency classification codes.
- Booth C, Romano R, Roncarolo MG, Thrasher AJ. Gene therapy for primary immunodeficiency. Hum Mol Genet. 2019;28(R1):R15-R23.
- British National Formulary (BNF) for Children. Monograph: autologous CD34+ enriched cell fraction transduced with retroviral vector encoding the human ADA cDNA sequence. Updated 2025.
About the Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialists in pediatric immunology, hematology, gene therapy and pharmacology. Our content follows the GRADE evidence framework and is based on peer-reviewed research, international clinical guidelines (EMA, ESID, EBMT, IUIS) and established medical standards.
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