部份中文Strimvelis处方资料（仅供参考）
英文名: Autologous CD34+enriched cell human adenosine deaminase (ADA)
商品名：Strimvelis
中文名：自体CD34+细胞转导表达腺苷脱氨酶(ADA)
活性物质: 自体CD34+富集细胞分数, 包含CD34+细胞转基因与逆转录病毒载体, 编码的人腺苷脱氨酶 (ADA) cDNA 序列从人类造血茎/祖(CD34+)细胞
权持人: 葛兰素有限公司
批准日期: 2016年5月26日
分类名称: 免疫增强剂
适应症
Strimvelis为治疗严重联合免疫机能丧失症, 由于腺苷脱氨酶缺乏 (ADA), 为谁没有合适的人白细胞抗原 (HLA) 匹配的相关干细胞捐献者可用。
包装规格
输液
Strimvelis:1-10million 细胞/毫升分散剂
Strimvelis (Autologous CD34+ enriched cell fraction transduced that encodes for human adenosine deaminase (ADA))
Strimvelis
GlaxoSmithKline UK
Active ingredient
autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes for the human ADA cDNA sequence
Legal Category
POM: Prescription only medicine
1. Name of the medicinal product
Strimvelis 1-10million cells/ml dispersion for infusion.
2. Qualitative and quantitative composition
2.1 General description
An autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase (ADA) cDNA sequence from human haematopoietic stem/progenitor (CD34+) cells.
2.2 Qualitative and quantitative composition
The finished product is composed of one or more ethylene vinyl acetate (EVA) bags which contain an autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector that encodes for the human ADA cDNA sequence.
The quantitative information regarding CD34+ cells/kg and total cells in the product is presented in the labelling for each batch. The concentration is 1-10 million CD34+ cells/ml.
Excipient with known effect
This medicinal product contains 0.15 mmol sodium per ml (see section 4.4).
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Dispersion for infusion.
A cloudy to clear, colourless to pink dispersion of cells.
4. Clinical particulars
4.1 Therapeutic indications
Strimvelis is indicated for the treatment of patients with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID), for whom no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available (see section 4.2 and section 4.4).
4.2 Posology and method of administration
Strimvelis must be administered in a specialist transplant centre, by a physician with previous experience in the treatment and management of patients with ADA-SCID and in the use of autologous CD34+ ex vivo gene therapy products. Strimvelis should only be administered after consultation with the patient and/or family. Patients are expected to enrol in a post-treatment registry and will be followed-up long term.
A CD34+ stem cell back-up containing at least 1 million CD34+ cells per kg is required. This should be harvested from the patient at least 3 weeks prior to treatment with Strimvelis. The stem cell back-up is collected for use as rescue treatment should there be a failure during product manufacture, transplant failure, or prolonged bone marrow aplasia after treatment with Strimvelis.
The patient must be able to donate adequate CD34+ cells to deliver the minimum 4 million purified CD34+ cells/kg, required for manufacture of Strimvelis.
Strimvelis is intended for autologous use only (see section 4.4).
Before infusion, it must be confirmed that the patient's identity matches the essential unique patient information on the Strimvelis infusion bag(s) and/or container (see sections 4.4 and 6.6).
Pre-treatment conditioning
It is recommended that 0.5 mg/kg intravenous busulfan be administered every 6 hours on two consecutive days starting three days before administration of Strimvelis. The total busulfan dose is 4 mg/kg, divided into 8 doses of 0.5 mg/kg. Busulfan plasma levels should be measured after the first dose of each day by serial blood sampling using an appropriate method. If busulfan AUC exceeds 4000 nanograms/ml*h (974 µmol/L.minute), the dose should be appropriately reduced based on the AUC.
Premedication
It is recommended that an intravenous antihistamine be administered 15-30 minutes before the infusion of Strimvelis.
Posology
The recommended dose range of Strimvelis is between 2 and 20 million CD34+ cells/kg.
If the product contains less than 2 million CD34+ cells/kg, the treating physician should make a decision whether to proceed with administration, based on an individual benefit risk assessment. Treatment failure was observed in a patient treated in the clinical trials with <2 millions CD34+cell/kg.
Strimvelis should be administered once only.
Special populations
Elderly
Strimvelis is not intended for use in patients >65 years of age, and has not been studied in this age group.
Renal impairment
Strimvelis has not been studied in patients with renal impairment. No dose adjustment is expected to be required.
Hepatic impairment
Strimvelis has not been studied in patients with hepatic impairment. No dose adjustment is expected to be required.
Paediatric population
The safety and efficacy of Strimvelis in children less than six months of age or over 6 years 1 month has not been established (see section 4.4). No data are available.
Method of administration
Strimvelis is for intravenous infusion.
A transfusion administration set with filter should be used. Only filters intended for use with transfusion sets should be used to prevent inadvertent removal of cells from the product.
The infusion rate should not exceed 5 ml/kg/h. The period of administration is approximately 20 minutes (see section 6.6). Following administration, a saline filled 50 ml syringe should be used to flush the bag through.
Precautions to be taken before manipulating or administering the product
This medicinal product contains genetically-modified cells. Local biosafety guidelines applicable for such products should be followed (see section 6.6).
Strimvelis is not tested for transmissible infectious agents. Healthcare professionals handling Strimvelis should therefore take appropriate precautions to avoid potential transmission of infectious diseases.
4.3 Contraindications
Hypersensitivity to the product or to any of the excipients listed in section 6.1.
Current or previous history of leukaemia or myelodysplasia.
Positive test for human immunodeficiency virus (HIV) or presence of any other transmissible infectious agent listed in the current EU Cell and Tissue Directive prior to bone marrow harvest.
History of previous gene therapy.
4.4 Special warnings and precautions for use
Strimvelis is intended solely for autologous use and should never be administered to any patient other than the original CD34+ cell donor.
In some cases the patient may be unable to receive Strimvelis because of manufacturing issues. After notification, the treating physician may need to modify the treatment program of the patient accordingly (i.e. terminating the busulfan conditioning and/or administration of the stem cell back up treatment if appropriate).
Stage two quality control results will only be available after the product has been infused. If clinically relevant quality issues, such as out of specification results, are identified after Strimvelis has been infused, the treating physician will be notified. The physician should monitor and/or treat the patient as appropriate.
Strimvelis should be used with caution in patients older than 6 years and 1 month and younger than 6 months as there are no data from clinical trials in these age ranges. Older patients are typically less able to donate high numbers of CD34+ cells which may mean that older patients cannot be treated. Successful generation of T cells after Strimvelis is also likely to be affected by residual thymic function which can become impaired in older children. Use of Strimvelis in patients older than those previously studied should be carefully considered and reserved only for occasions where all other reasonable treatment options have been exhausted.
Patients who have previously tested positive for hepatitis C can be treated with Strimvelis, provided they demonstrate absence of ongoing infection using a nucleic acid test with a limit of quantification of ≤15 international units/ml. Negative test results are required on at least 3 sequential occasions over a period of at least 4 weeks, after completion of treatment for hepatitis C, with the final test conducted no more than 3 days prior to cell harvest.
Strimvelis should be used with caution in patients with hypersensitivity to aminoglycosides or bovine serum albumin.
No cases of leukaemia or myelodysplasia have been reported following treatment with Strimvelis. However, vector insertions into chromosomal regions previously associated with leukaemia in comparable trials of gene therapy in Wiskott Aldrich Syndrome, X-SCID and Chronic Granulomatous Disease have been documented. Retroviral insertion sites (RIS) have been detected adjacent to or within CCND2 and LMO2 and there is a potential risk of leukaemic transformation following treatment with Strimvelis. It is recommended that patients be monitored long term with at least annual visits for the first eleven years and then at 13 and 15 years post treatment with Strimvelis, to include a complete blood count with differential, biochemistry and thyroid stimulating hormone.
The long term effects and durability of response to Strimvelis on ADA-SCID are unknown (see section 5.1).
Patients should be closely monitored for the occurrence of severe and opportunistic infections, immune reconstitution parameters and the need for replacement intravenous immunoglobulin (IVIG); in case of lack of response, it is recommended to introduce other ADA-SCID treatments under the supervision of a physician.
There have been cases where treatment with Strimvelis has been unsuccessful. Some patients have had to resume long-term enzyme replacement therapy and/or receive a stem cell transplant (see section 5.1).
Non-immunological manifestations of ADA-SCID may not respond to Strimvelis.
No immunogenicity testing has been conducted with Strimvelis.
Patients can develop autoimmunity. 67% (12 of 18) of Strimvelis treated patients had either autoimmune antibodies or other manifestations (e.g. autoimmune thrombocytopenia, autoimmune aplastic anaemia, autoimmune hepatitis and Guillain-Barré syndrome) (see section 4.8).
Patients treated with Strimvelis should not donate blood, organs, tissues and cells for transplantation, at any time in the future. This information is provided in the Patient Alert Card.
T-lymphocyte (CD3+) and NK (CD56+) cell counts improved following treatment with Strimvelis. Median values at 3 years post gene therapy were below the normal range. Continued follow-up is recommended. Cases of skin papillomas, abnormal serum protein electrophoresis and one case each of lipofibroma, pulmonary mass and decreased T-cell V beta repertoire were reported. No evidence of causality to the product has been established.
Adverse events related to the use of central venous catheters (CVCs) have been reported (e.g., serious CVC infections and thrombosis in the device). Patients should be closely monitored for potential catheter-related events.
Sodium content
This medicinal product contains 0.15 mmol sodium per ml. To be taken into consideration by patients on a controlled sodium diet.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed. Strimvelis is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential
As Strimvelis will be administered following busulfan conditioning, patients of childbearing potential must use reliable barrier contraception during administration of Strimvelis and for at least 6 months afterwards.
Pregnancy
No clinical data on exposed pregnancies are available.
Reproductive and developmental toxicity studies were not performed.
Strimvelis should not be used during pregnancy.
Breast-feeding
It is unknown whether Strimvelis is excreted in human milk. The effect on breast-fed infants of administration of Strimvelis to their mothers has not been studied.
Strimvelis should not be administered to women who are breast-feeding.
Fertility
There are no data on the effects of Strimvelis on human fertility. Effects on male and female fertility have not been evaluated in animal studies.
4.7 Effects on ability to drive and use machines
Strimvelis has no or negligible long term influence on the ability to drive and use machines.
4.8 Undesirable effects
Summary of the safety profile
The safety of Strimvelis was evaluated in 18 subjects, with a median duration of follow-up of 7 years.
Given the small patient population and size of the cohorts, adverse reactions in the table do not provide a complete perspective on the nature and frequency of these events. Serious adverse reactions include autoimmunity (e.g. autoimmune haemolytic anaemia, autoimmune aplastic anaemia, autoimmune hepatitis, autoimmune thrombocytopenia and Guillain-Barré syndrome). The most commonly reported adverse reaction was pyrexia.
Tabulated list of adverse reactions
Adverse reactions are listed below by MedDRA body system organ class and by frequency. The frequency categories used are:
Very common  ≥ 1/10
Common  ≥1/100 to <1/10
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

System organ class	Very common	Common
Blood and lymphatic system disorders	Anaemiaa Neutropeniaa	Autoimmune haemolytic anaemia, autoimmune aplastic anaemia, autoimmune thrombocytopenia
Endocrine disorders	Hypothyroidism	Autoimmune thyroiditis
Nervous system disorders		Guillain-Barré syndrome
Vascular disorders	Hypertensiona
Respiratory, thoracic and mediastinal disorders	Asthma, rhinitis allergic
Hepatobiliary disorders		Autoimmune hepatitis
Skin and subcutaneous tissue disorders	Dermatitis atopic, eczema
General disorders and administration site conditions	Pyrexia
Investigations	Hepatic enzyme increaseda, antinuclear antibody (ANA) positive	Antineutrophil cytoplasmic antibody positive, smooth muscle antibody positive

aAdverse reactions considered potentially related to busulfan conditioning
Description of selected adverse reactions
Immune reconstitution
All the identified adverse reactions in the table (apart from those potentially related to busulfan) are considered to be related to immune reconstitution, due to their nature and timing. These autoimmune adverse reactions were reported for subjects post-gene therapy. The majority were reported during the 3 month to 3 year follow-up period and resolved, with the exception of hypothyroidism and positive ANA tests. In addition, the allergy related adverse reactions in the table were reported mostly during the 3 month to 3 year follow-up period.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store
Ireland
HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517.
Website: www.hpra.ie; E-mail: medsafety@hpra.ie
4.9 Overdose
No data from clinical studies are available regarding overdose of Strimvelis.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Immunostimulants, other immunostimulants , ATC code: not yet assigned
Mechanism of action
After infusion, CD34+ cells engraft in the bone marrow where they repopulate the haematopoetic system with a proportion of cells that express pharmacologically active levels of the ADA enzyme.
Following successful engraftment in the patient, the effects of the product are expected to be life-long.
Pharmacodynamic effects
The median percentages of genetically modified cells in peripheral blood at one year and 3 years after treatment were 28% (range 6%-92%) and 30% (range 8%-101%) of CD19+, and 73% (range 20%-100%) and 67% (range 39%-82%) of CD3+ cells, respectively.
The presence of the transgene leads to increased expression of ADA. One year post treatment, median ADA activity (mononuclear cells adenosine deaminase) in peripheral blood lymphocytes was 181.2 (range 42.1-1678.2) nmol/h/mg protein, compared to a baseline median (range) of 80.6 (30.5-92.3) nmol/h/mg protein. ADA activity remained increased throughout the duration of the 3 year follow up.
Clinical efficacy and safety
A total of 18 patients with ADA-SCID were treated with Strimvelis as part of one open-label pivotal trial (AD1115611; N=12), two early open-label pilot studies (AD1117054/AD1117056; N=3), and a compassionate use program (AD1117064; N=3). Studies evaluated the use of Strimvelis with a range of 0.9 million – 18.2 million CD34+ cells/kg. All patients received busulfan conditioning prior to gene therapy, with most receiving a total dose of 4 mg/kg intravenously over 2 consecutive days prior to CD34+ infusion. Four subjects had previously received an unsuccessful stem cell transplant from a haploidentical donor and 15 of 18 subjects had previously received prior enzyme replacement therapy with polyethylene-glycol-modified bovine adenosine deaminase (PEG-ADA). Patients who previously received PEG-ADA had this treatment withdrawn 10 to 22 days prior to Strimvelis therapy. The median age across the program was 1.7 years (range 0.5 to 6.1) and 61% were males. Eighty three percent were white (56% Caucasian/European heritage and 28% Arabic/North African heritage), 11% African American/African, and 6% Asian.
Patients treated within the pivotal study
The efficacy of Strimvelis was evaluated in a 3-year open-label, prospective study in children who lacked a sibling HLA matched stem cell donor and were either failing to respond adequately to PEG-ADA, were intolerant or did not have access to it.
Results at 3 years for patients treated within the pivotal study are presented in Table 1. Treatment with Strimvelis resulted in a 100% survival rate at 3 years post therapy, a decrease in the severe infection rate, an increase in T-lymphocytes (CD3+) and all subjects having post-baseline venous red blood cell deoxyadenosine nucleotide (RBC dAXP) levels below pathological levels (>100 nmol/ml).
Table 1. Results at 3 years for the ITT population in the pivotal study*

Endpoint	Baseline/ Pre-Treatmenta	Year 3/ 3 Years Post-Treatmentb
Survival n %	Not applicable	12 100%
Severe infections n Rate of severe infections per person-year of observation (95% confidence interval)	12 1.10 (0.74-1.58)	12 0.429 c (0.24-0.72)
T-lymphocyte (x106/l) n median (range)	11 88.0 (19-2718)	11 828.0 (309-2458)
% subjects with venous RBC dAXP <100 nmol/ml after Strimvelisd n %	Not applicablee	11 100%

Including data from one patient collected post intervention with PEG-ADA (≥3 months treatment) or hematopoietic stem cell transplantation
a Based on the entire pre-treatment period for severe infections (retrospectively collected), and the data collected at the baseline visit for T-lymphocytes. Patient 10 had no baseline value for T-lymphocytes.
b Based on the 3 year post-treatment period for survival and severe infections, and the data collected at the 3 year visit for T-lymphocytes and dAXP. Patient 8 withdrew from the study before 3 year visit, and thus had no data for T-lymphocytes and dAXP.
c Severe infections are those requiring or prolonging hospitalisation. The 3 month hospitalisation period immediately post gene therapy was excluded from the calculation
d dAXP=dAMP+dADP+dATP. dAXP results are based on a responder analysis of the percentage of patients following gene therapy who met the definition of adequate metabolic detoxification, therefore baseline value is not applicable.
e At baseline 9 of 11 (82%) patients had dAXP <100 nmol/ml. All these patients had previously taken PEG-ADA.
T cell function: In the patients treated in the pivotal study, T cell proliferation was demonstrated in response to stimulation with anti-CD3 antibodies (median 62629 cpm, range 4531 to 252173) and phytohemaglutinin (median 140642 cpm, range 11119 to 505607) at 1 year post gene therapy, and these responses were sustained through Year 3. Findings that TREC (T cell receptor excision circles) in peripheral blood lymphocytes were increased above baseline (median 141, range 56 to 1542 copies/100ng DNA) at Years 1 and maintained to 3 post-treatment and that all subjects had evidence of polyclonal V-beta chains at one or more time points following gene therapy provides further supportive evidence of functional T cell development.
B cell function: All 12 subjects treated in the pivotal study were receiving IVIG therapy at the time of screening, and 7 subjects (58%) had discontinued IVIG use during 0-3 years follow-up after gene therapy.
Long-term follow-up
A 100% survival rate was observed for all 12 subjects treated within the pivotal study and also for the 18 subjects in the integrated analysis, with a median follow up duration of approximately 7 years. Intervention-free survival in this pivotal population (defined as survival without the requirement for long-term (≥3 month) re-introduction of PEG-ADA, or stem cell transplant) was 92% (11/12 subjects) (82% (14/17 subjects) for integrated population). One subject treated in a pilot study did not have PEG-ADA re-introduction data, and thus was excluded from the intervention-free survival in the integrated population. Long-term PEG-ADA (exceeding 3 months of continuous duration) was used by three subjects; two of these subjects subsequently received a sibling-matched stem cell transplant and one subject remained on chronic PEG-ADA treatment. Another subject needed transient PEG-ADA administration due to an autoimmune event (see section 4.4).
In those patients treated in the pivotal study, the rate of severe infections declined throughout the follow-up period (Table 2).
Table 2 Rate of severe infections per person year of exposure (pivotal population)

Pre treatment	Post treatment
Time period (Years)	n/a	0.33-1	>1-2	>2-3	>3-4	>4-5	>5-6	>6-7	>7-8	Total
No. of subjects	12	12	11	11	11	11	9	7	3	12
No. of severe infections	29	6	3	0	2	0	1	0	0	12
Rate of severe infections per person year	1.10	0.63	0.27	0.00	0.18	0.00	0.12	0.00	0.00	0.17

Excluding data from one patient collected from the time of intervention with PEG-ADA (≥3 months treatment) or hematopoietic stem cell transplantation. n/a – not applicable.
5.2 Pharmacokinetic properties
Strimvelis is an autologous cellular therapy. The nature of Strimvelis is such that conventional studies on pharmacokinetics, absorption, distribution, metabolism, and elimination are not applicable.
5.3 Preclinical safety data
Reproductive and developmental studies have not been conducted.
A 4-month biodistribution study was performed in mice. CD34+ cells derived from healthy human umbilical cord blood, transduced with the vector used for the production of Strimvelis, were administered intravenously to busulfan-conditioned mice. The majority of mice showed reconstitution of the haematopoietic system by the end of the study. Low levels of human cells and vector sequences were also detected in non-haematopoietic organs consistent with the presence of blood containing transduced human cells. There were no adverse effects on survival, haematological parameters or histopathology of major organs, apart from body weight loss and atrophy in the testes and ovaries consistent with administration of busulfan.
Carcinogenicity studies have not been conducted as no adequate animal model was available to evaluate the tumourigenic potential of Strimvelis due to the inability to achieve long-term engraftment of transduced cells in mice.
6. Pharmaceutical particulars
6.1 List of excipients
Sodium chloride
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
6.3 Shelf life
6 hours.
6.4 Special precautions for storage
Store at 15-30°C.
6.5 Nature and contents of container
50 ml ethylene vinyl acetate (EVA) infusion bag, with a luer spike interconnector closed with a luer lock cap, packed in a re-usable outer container.
6.6 Special precautions for disposal and other handling
Strimvelis is transported directly to the medical facility where the infusion will be administered. The infusion bag(s) is/are placed inside a closed outer container. The bags must be kept in the outer container until ready to use.
Strimvelis is intended solely for autologous use. The identity of the patient must be matched with the essential unique patient information on the primary and/or outer container prior to infusion.
Gently agitate the infusion bag to re-disperse any cellular aggregates, administer using a transfusion administration set with filter to remove any remaining cellular aggregates.
This medicinal product contains genetically-modified cells. Local biosafety guidelines applicable should be followed (see section 4.2).
Strimvelis is not tested for transmissible infectious agents. Healthcare professionals handling Strimvelis should therefore take appropriate precautions to avoid potential transmission of infectious diseases.
Work surfaces and material which have potentially been in contact with Strimvelis must be decontaminated with appropriate disinfectant.
Any unused medicinal product or waste material should be disposed of in accordance with local biosafety requirements.
7. Marketing authorisation holder
GlaxoSmithKline Trading Services Limited
Currabinny
Carrigaline
County Cork
Ireland
8. Marketing authorisation number(s)
EU/1/16/1097/001
9. Date of first authorisation/renewal of the authorisation
26 May 2016
10. Date of revision of the text
20 July 2017
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.
干细胞基因疗法Strimvelis获欧盟批准治疗ADA-SCID
  近日，欧盟委员会（EC）批准Strimvelis用于腺苷脱氨酶（ADA）缺乏性重度联合免疫缺陷症（ADA-SCID）儿科患者。ADA-SCID是一种非常罕见的疾病，患者出生时便不具备健康、健全的免疫系统功能，导致对日常感染失去抵抗力。据估计，在欧洲，每年大约确诊15例ADA-SCID儿科患者。Strimvelis的获批，开启了罕见遗传性疾病临床治疗的新篇章。
  Strimvelis（自体CD34+细胞转导表达腺苷脱氨酶（ADA））是首个离体（ex-vivo）干细胞基因疗法，也是全球获批的首个用于儿科患者的纠正性基因疗法，用于无合适人类白细胞抗原（HLA）相匹配干细胞捐献者的ADA-SCID患者的治疗。
  Strimvelis的获批，是基于来自18例儿科ADA-SCID患者接受Strimvelis治疗的数据。一项关键性研究（n=12）中，所有儿科ADA-SCID患者接受Strimvelis治疗后3年的存活率达100%；上市许可申请纳入的18例接受Strimvelis治疗的ADA-SCID患者目前仍然存活，中位随访时间为7年。完整的数据分析已于近日发表于国际期刊《血液》（BLOOD）。
  Strimvelis只需给药一次，而且不依赖于第三方捐献者，因此不存在因排斥（移植物抗宿主病）引发的免疫不相容风险，这是骨髓移植治疗中常见的副作用。Strimvelis基因疗法，首先从患者的骨髓中取出干细胞，通过转导将一个正常拷贝的ADA基因导入干细胞，然后采取静脉输注将干细胞重新导入患者体内，之后一部分干细胞会归巢至骨髓。采取Strimvelis治疗时，为了提高基因修饰后干细胞的定植，患者事先需要进行低剂量化疗治疗。