**2. Who, when, what to transplant**

SCID is one of the most severe forms of PID. Early diagnosis and management are essential and HSCT is curative. For other forms of PID, management and in particular the indications for HSCT are evolving. New data is emerging on the natural history of patients with diseases such as CGD and CD40L deficiency and the outcome from HSCT has improved dramatically and so the risks of performing HSCT at a young age before organ damage from recurrent infection and inflammation need to be carefully assessed and discussed with families balanced against a potentially shortened life span with poor quality of life due to multiple hospital admissions.

Stem Cell Transplantation for Primary Immunodeficiency 5

Abbreviations: CγC Common gamma chain, XL X linked, Jak 3 Janus associated kinase 3, AR Autosomal recessive, ADA Adenosine deaminase, RAG Recombinant activating gene, MHC Major histocompatibility, PNP Purine nucleoside phosphorylase, IPEX Immunodeficiency polyendocrinopathy enteropathy X linked, CHARGE coloboma, heart anomalies, choanal atresia, retardation of growth and development, and genital and ear anomalies due to CHD7

gene mutations.

\*\*Not all require HSCT

\*Thymic transplant recommended in preference to HSCT

**Table 1.** Indications for HSCT in immunodeficiencies

Table 1 gives a current list of primary immunodeficiency diseases in which HSCT is indicated.

#### **2.1. Importance of molecular diagnosis**

Precise molecular diagnosis is very helpful as prognosis can then be accurately assessed. The outcome following HSCT for patients with B negative forms of SCID such as RAG deficiency is less good than for those with B positive forms. Furthermore those with artemis deficiency have a worse prognosis than those with RAG deficiency because of the associated cellular radiosensitivity. In the long term post HSCT human papilloma virus warts predominantly occur in patients with common gamma chain or JAK3 deficient SCID[10], but not other SCID genotypes.

Ill-defined combined immunodeficiencies (CID) are a challenge to treat, as the outcome with HSCT is variable, and often poor[8]. This is because, at least in part, decisions about when to transplant are not made until a disease-defining illness has occurred (Table 2), which may leave significant organ damage or a persisting viral burden, which alters the prognosis following transplantation. Identification of a specific gene defect in a patient cohort can alter management decisions. For example, clear molecular definition has changed the management of an autosomal recessive form of hyper IgE syndrome caused by mutations in the dedicator of the cytokinesis 8 (DOCK8) gene. Previously this disease was managed conservatively, as a form of hyper IgE syndrome. Accurate molecular definition enabled data to be gathered on a patient cohort leading to the realisation that there is a high risk of infection, skin malignancy and death. Reports of cases being successfully transplanted have lead to HSCT becoming the treatment of choice for this diagnosis.[11-15]

Reticular dysgenesis is an autosomal recessive form of SCID characterised by an early differentiation arrest in myeloid lineage and impaired lymphoid maturation. Affected individuals also have bilateral sensorineural deafness. Mutations in AK2 (adenylate kinase 2) published in 2008 demonstrated that AK2 is expressed in the stria vascularis region of the inner ear providing an explanation for the deafness in addition to it's role in specific haematopoietic lineages. Again this can lead to an earlier specific diagnosis and appropriate intervention.[16]


Abbreviations: CγC Common gamma chain, XL X linked, Jak 3 Janus associated kinase 3, AR Autosomal recessive, ADA Adenosine deaminase, RAG Recombinant activating gene, MHC Major histocompatibility, PNP Purine nucleoside phosphorylase, IPEX Immunodeficiency polyendocrinopathy enteropathy X linked, CHARGE coloboma, heart anomalies, choanal atresia, retardation of growth and development, and genital and ear anomalies due to CHD7 gene mutations.

\*Thymic transplant recommended in preference to HSCT \*\*Not all require HSCT

4 Immunodeficiency

indicated.

**2. Who, when, what to transplant** 

**2.1. Importance of molecular diagnosis** 

multiple hospital admissions.

but not other SCID genotypes.

intervention.[16]

SCID is one of the most severe forms of PID. Early diagnosis and management are essential and HSCT is curative. For other forms of PID, management and in particular the indications for HSCT are evolving. New data is emerging on the natural history of patients with diseases such as CGD and CD40L deficiency and the outcome from HSCT has improved dramatically and so the risks of performing HSCT at a young age before organ damage from recurrent infection and inflammation need to be carefully assessed and discussed with families balanced against a potentially shortened life span with poor quality of life due to

Table 1 gives a current list of primary immunodeficiency diseases in which HSCT is

Precise molecular diagnosis is very helpful as prognosis can then be accurately assessed. The outcome following HSCT for patients with B negative forms of SCID such as RAG deficiency is less good than for those with B positive forms. Furthermore those with artemis deficiency have a worse prognosis than those with RAG deficiency because of the associated cellular radiosensitivity. In the long term post HSCT human papilloma virus warts predominantly occur in patients with common gamma chain or JAK3 deficient SCID[10],

Ill-defined combined immunodeficiencies (CID) are a challenge to treat, as the outcome with HSCT is variable, and often poor[8]. This is because, at least in part, decisions about when to transplant are not made until a disease-defining illness has occurred (Table 2), which may leave significant organ damage or a persisting viral burden, which alters the prognosis following transplantation. Identification of a specific gene defect in a patient cohort can alter management decisions. For example, clear molecular definition has changed the management of an autosomal recessive form of hyper IgE syndrome caused by mutations in the dedicator of the cytokinesis 8 (DOCK8) gene. Previously this disease was managed conservatively, as a form of hyper IgE syndrome. Accurate molecular definition enabled data to be gathered on a patient cohort leading to the realisation that there is a high risk of infection, skin malignancy and death. Reports of cases being successfully transplanted have

Reticular dysgenesis is an autosomal recessive form of SCID characterised by an early differentiation arrest in myeloid lineage and impaired lymphoid maturation. Affected individuals also have bilateral sensorineural deafness. Mutations in AK2 (adenylate kinase 2) published in 2008 demonstrated that AK2 is expressed in the stria vascularis region of the inner ear providing an explanation for the deafness in addition to it's role in specific haematopoietic lineages. Again this can lead to an earlier specific diagnosis and appropriate

lead to HSCT becoming the treatment of choice for this diagnosis.[11-15]

**Table 1.** Indications for HSCT in immunodeficiencies

#### **2.2. Severe combined immunodeficiency**

Severe combined immunodeficiency is usually fatal by 1 year of age unless an infant receives a new immune system and should be considered a paediatric emergency which is immediately life threatening. In the most recent analysis of 699 SCID patients transplanted across Europe there was a survival of 90% for those transplanted with a genoidentical sibling donor and nearly 70% for those receiving a matched unrelated donor[8]. The outcome for those without pre-existing infection such as those diagnosed at birth is even better: in the UK series the survival for those transplanted having being diagnosed at or before birth was 91.5% compared to 61% for those transplanted having being diagnosed at a median age of 143 days and a significant number of these children died from infection before reaching transplant[5]. These data support neonatal screening programmes, which are being introduced in North America, and pick up patients with SCID in the newborn period, before infection supervenes[17]. Similar screening programmes are being considered in Europe. Recognition of the specific molecular defect may alter the approach to HSCT. Patients with adenosine deaminase-deficient SCID will develop adequate immunological reconstitution following an unconditioned infusion from HLA-identical sibling stem cells[18], whereas those with RAG-deficient SCID will require chemotherapy conditioning to achieve stem cell engraftment and immunological reconstitution.

Stem Cell Transplantation for Primary Immunodeficiency 7

none since the year 2000, and 3 out of the 4 deaths were in children over 12 years of age who already had sclerosing cholangitis. All the survivors express CD40L and only one needs immunoglobulin. These data further emphasize the importance of early age at transplant

For non-T cell immunodeficiencies, timing of transplantation has been more controversial, although with registry data becoming available, the natural history of disease on conventional treatment is becoming more clear. Lifelong antibacterial and antifungal prophylaxis with cotrimoxazole and itraconazole has improved short- and medium-term survival for patients with chronic granulomatous disease. However, although steroids and aminosalicylates ameliorate colitis and other inflammatory complications they do not cure the underlying genetic defect and longterm immunosuppression is required to maintain symptom control. Quality of life is poor with frequent hospital admissions and poor growth. Even with the best prophylactic treatment, only 50% of patients are alive at 30 years[6] (Figure 1). HSCT can cure CGD with resolution of infection and colitis but was previously considered to be a high risk procedure. A European multicenter experience of replete marrow HSCT with mainly matched sibling donor stem cells following myeloablative conditioning gave good results; 23/27 patients survived, 22 were cured (81%), with deaths confined to high-risk patients with active fungal infection[24]. A more recent single centre study demonstrated similar outcomes with either matched sibling or matched unrelated donors, with a survival and cure of 90% and low incidence of significant GvHD. Mean weight and height for age Z scores on recovery from HSCT rose significantly. Transplantassociated complications were restricted to those with pre-existing infection or inflammation, supporting the argument for early HSCT for all CGD patients with a well matched donor[25]. As transplantation techniques improve, and survival increases, earlier transplantation becomes a more attractive option for other primary immunodeficiencies

requiring long term antimicrobials and immunosuppression to control symptoms.

Unlike patients with haematological malignancy in whom a graft versus leukaemia effect is desirable, GVHD confers no benefit to patients with PID. The best HLA matched donor is a sibling and so any siblings of the patient should be tissue typed. Many PID patients come from consanguineous families and so it may be possible to find a donor from the extended family. When tissue typing reveals more than one possible donor, other factors such as age, sex, parity, blood group and cytomegalovirus (CMV) status are taken into consideration. If no family donor is found a search of the National and International unrelated donor registries should be undertaken. There are currently 19 million adult and over 500,000 cord blood donors that can be accessed through the Bone Marrow Donors Worldwide registry

Bone marrow has been the traditional source of stem cells and is harvested under general anaesthetic from the posterior iliac crests. Adult donors are increasingly being offered the

**2.4. Donor choice and degree of HLA matching** 

(www.bmdw.org).

**3. Stem cell source** 

before organ damage supervenes.

#### **2.3. Other primary immunodeficiencies**

For other non-SCID PID, debate continues about the optimum age for transplantation. As registry data for specific diseases becomes available, the role of HSCT is increasingly clear, but the optimum age for transplantation remains to be determined. Earlier transplantation is favoured for T cell immunodeficiencies.

Filipovich et al published results of 170 transplants for Wiskott Aldrich syndrome and demonstrated that boys receiving an unrelated donor transplant before the age of 5 had as high a survival rate to matched sibling donor recipients of any age[19]. A recent international report of 194 patients with Wiskott Aldrich syndrome, transplanted in 12 centers, reported an overall survival of 84%, rising to 89% for those transplanted since the year 2000. Younger age and milder clinical phenotype was associated with better outcome[20]. Whilst survival has improved over the last decade, young age at transplant before complications of the underlying disease supervene, also improves outcome.[21]

The outcome of patients transplanted for CD40 ligand deficiency is also dependent on age at transplantation, with pre-existing lung disease being a significant factor in predicting survival[22, 23]. Thirty eight children were reported who were transplanted in Europe for CD40L between 1993 and 2002. Of the 34 engrafted, 26 survived (68%), and 20 no longer required immunoglobulin replacement therapy. This survival and cure rate was little better than the survival of non-transplanted patients at the age of 20 years. However, many patients in this series were over 10 years of age when transplanted and already had significant lung and/or liver damage. A total of 14 patients with CD40L deficiency have been transplanted in our centre: 2 received MSD and 10 URD; 4 died (overall survival 71%), but none since the year 2000, and 3 out of the 4 deaths were in children over 12 years of age who already had sclerosing cholangitis. All the survivors express CD40L and only one needs immunoglobulin. These data further emphasize the importance of early age at transplant before organ damage supervenes.

For non-T cell immunodeficiencies, timing of transplantation has been more controversial, although with registry data becoming available, the natural history of disease on conventional treatment is becoming more clear. Lifelong antibacterial and antifungal prophylaxis with cotrimoxazole and itraconazole has improved short- and medium-term survival for patients with chronic granulomatous disease. However, although steroids and aminosalicylates ameliorate colitis and other inflammatory complications they do not cure the underlying genetic defect and longterm immunosuppression is required to maintain symptom control. Quality of life is poor with frequent hospital admissions and poor growth. Even with the best prophylactic treatment, only 50% of patients are alive at 30 years[6] (Figure 1). HSCT can cure CGD with resolution of infection and colitis but was previously considered to be a high risk procedure. A European multicenter experience of replete marrow HSCT with mainly matched sibling donor stem cells following myeloablative conditioning gave good results; 23/27 patients survived, 22 were cured (81%), with deaths confined to high-risk patients with active fungal infection[24]. A more recent single centre study demonstrated similar outcomes with either matched sibling or matched unrelated donors, with a survival and cure of 90% and low incidence of significant GvHD. Mean weight and height for age Z scores on recovery from HSCT rose significantly. Transplantassociated complications were restricted to those with pre-existing infection or inflammation, supporting the argument for early HSCT for all CGD patients with a well matched donor[25]. As transplantation techniques improve, and survival increases, earlier transplantation becomes a more attractive option for other primary immunodeficiencies requiring long term antimicrobials and immunosuppression to control symptoms.

#### **2.4. Donor choice and degree of HLA matching**

Unlike patients with haematological malignancy in whom a graft versus leukaemia effect is desirable, GVHD confers no benefit to patients with PID. The best HLA matched donor is a sibling and so any siblings of the patient should be tissue typed. Many PID patients come from consanguineous families and so it may be possible to find a donor from the extended family. When tissue typing reveals more than one possible donor, other factors such as age, sex, parity, blood group and cytomegalovirus (CMV) status are taken into consideration. If no family donor is found a search of the National and International unrelated donor registries should be undertaken. There are currently 19 million adult and over 500,000 cord blood donors that can be accessed through the Bone Marrow Donors Worldwide registry (www.bmdw.org).

#### **3. Stem cell source**

6 Immunodeficiency

**2.2. Severe combined immunodeficiency** 

to achieve stem cell engraftment and immunological reconstitution.

**2.3. Other primary immunodeficiencies** 

favoured for T cell immunodeficiencies.

Severe combined immunodeficiency is usually fatal by 1 year of age unless an infant receives a new immune system and should be considered a paediatric emergency which is immediately life threatening. In the most recent analysis of 699 SCID patients transplanted across Europe there was a survival of 90% for those transplanted with a genoidentical sibling donor and nearly 70% for those receiving a matched unrelated donor[8]. The outcome for those without pre-existing infection such as those diagnosed at birth is even better: in the UK series the survival for those transplanted having being diagnosed at or before birth was 91.5% compared to 61% for those transplanted having being diagnosed at a median age of 143 days and a significant number of these children died from infection before reaching transplant[5]. These data support neonatal screening programmes, which are being introduced in North America, and pick up patients with SCID in the newborn period, before infection supervenes[17]. Similar screening programmes are being considered in Europe. Recognition of the specific molecular defect may alter the approach to HSCT. Patients with adenosine deaminase-deficient SCID will develop adequate immunological reconstitution following an unconditioned infusion from HLA-identical sibling stem cells[18], whereas those with RAG-deficient SCID will require chemotherapy conditioning

For other non-SCID PID, debate continues about the optimum age for transplantation. As registry data for specific diseases becomes available, the role of HSCT is increasingly clear, but the optimum age for transplantation remains to be determined. Earlier transplantation is

Filipovich et al published results of 170 transplants for Wiskott Aldrich syndrome and demonstrated that boys receiving an unrelated donor transplant before the age of 5 had as high a survival rate to matched sibling donor recipients of any age[19]. A recent international report of 194 patients with Wiskott Aldrich syndrome, transplanted in 12 centers, reported an overall survival of 84%, rising to 89% for those transplanted since the year 2000. Younger age and milder clinical phenotype was associated with better outcome[20]. Whilst survival has improved over the last decade, young age at transplant before complications of the underlying disease supervene, also improves outcome.[21]

The outcome of patients transplanted for CD40 ligand deficiency is also dependent on age at transplantation, with pre-existing lung disease being a significant factor in predicting survival[22, 23]. Thirty eight children were reported who were transplanted in Europe for CD40L between 1993 and 2002. Of the 34 engrafted, 26 survived (68%), and 20 no longer required immunoglobulin replacement therapy. This survival and cure rate was little better than the survival of non-transplanted patients at the age of 20 years. However, many patients in this series were over 10 years of age when transplanted and already had significant lung and/or liver damage. A total of 14 patients with CD40L deficiency have been transplanted in our centre: 2 received MSD and 10 URD; 4 died (overall survival 71%), but

Bone marrow has been the traditional source of stem cells and is harvested under general anaesthetic from the posterior iliac crests. Adult donors are increasingly being offered the

option of donating peripheral blood stem cells (PBSC) rather than bone marrow. This may be especially useful for donors who may have a medical condition of their own that would increase the risks of general anaesthesia. PBSC collection is generally carried out as a day case procedure and some donors find this prospect less difficult than the short period of hospitalisation and general anaesthetic needed for bone marrow donation. However, PBSC will require the donor to receive a short course of injections of granulocyte-colony stimulating factor (G-CSF) prior to commencing the first collection. Typically G-CSF at 10 micrograms per kilogram is given daily for 5 days before 1-2 leukapheresis procedures are performed. This procedure is not licensed in children in most countries and so sibling donations from children continue to be bone marrow.

Stem Cell Transplantation for Primary Immunodeficiency 9

Disadvantages of UCSCT include

**4. Assessment of donor** 

• Vaccination history • blood transfusion history

• history of travel to tropical countries • number of pregnancies in women

• allergy history

including:

i. low stem cell dose, particularly for an older child,

ii. Lack of availability of the donor should any boost procedure be required

engraftment which increases the risks from pre-existing infections.

serotherapy enables viral clearance, albeit with an increased risk of GvHD[26].

complete donor chimerism at day 100 and faster total lymphocyte recovery.[27]

iii. Cord blood units are virologically naïve and have been reported to have slower

However, the conditioning regimen employed may influence this, as omission of

For PID patients who often present before 1 year of age, UCSCT can offer a suitable stem cell source. In a recent European study mismatched-related donor HSCT was compared to unrelated donor cord HSCT in children with severe T cell deficiencies. There was no significant difference in survival, but cord blood recipients had a higher frequency of

A Physician or Paediatrician who is independent to that of the recipient should perform a pre-transplant assessment of any family donor. A medical history should be taken

A routine physical examination is performed and a chest radiograph and ECG if indicated.

For unrelated donors the examination is performed by the donor assessment centre. However the transplant centre will need to request blood for confirmatory tissue typing, DNA analysis for post transplant chimerism studies and the opportunity is usually taken to check the donor virology and serology status. The donor's fitness to donate must be ascertained before conditioning of the patient begins. The donor centre is responsible for the consent of the donor. The donor needs to be fully informed about the procedure for collecting the stem cells, the blood tests that will be performed including HIV status, the possibility of a second donation for the same patient and the emphasis on anonymity for the donor and patient. Anonymity may be relaxed in time and regulations may vary in different countries.

For related donors in the UK in addition to a physical examination, under the Human Tissue Act 2004, any potential donation of bone marrow or PBSC from adults who lack capacity to consent and children who lack competence to consent, must be assessed by an Accredited

Psychological aspects for the donor are important particularly when children are donating for siblings, for example if the recipient does not survive the donor may feel it is their fault.

Assessor and a report submitted to the Human Tissue Authority for consideration.

Therefore preparation and counselling for the donor is important

(Permission granted from Jones, *et al*6. Copyright by John Wiley and Sons, Ltd.)

**Figure 1.** Kaplan–Meier survival estimates, by sex for UK patients with chronic granulomatous disease.

Umbilical cord blood stem cell transplantation (UCSCT) offers a stem cell source when a matched sibling donor is unavailable.

Advantages of UCSCT include


Additionally, the HSC telomere length is longer in patients who have received UCSC than in those who have received PBSC from older donors. UCSCs may have greater self renewing capacity and longevity than those derived from an adult donor. As many transplanted PID patients are infants or young children, giving HSC with a greater proliferative life span is theoretically more attractive.

Disadvantages of UCSCT include

8 Immunodeficiency

option of donating peripheral blood stem cells (PBSC) rather than bone marrow. This may be especially useful for donors who may have a medical condition of their own that would increase the risks of general anaesthesia. PBSC collection is generally carried out as a day case procedure and some donors find this prospect less difficult than the short period of hospitalisation and general anaesthetic needed for bone marrow donation. However, PBSC will require the donor to receive a short course of injections of granulocyte-colony stimulating factor (G-CSF) prior to commencing the first collection. Typically G-CSF at 10 micrograms per kilogram is given daily for 5 days before 1-2 leukapheresis procedures are performed. This procedure is not licensed in children in most countries and so sibling

donations from children continue to be bone marrow.

(Permission granted from Jones, *et al*6. Copyright by John Wiley and Sons, Ltd.)

iv. higher chance of matching rare HLA haplotypes.

matched sibling donor is unavailable.

Advantages of UCSCT include

ii. absence of risk to donor

theoretically more attractive.

**Figure 1.** Kaplan–Meier survival estimates, by sex for UK patients with chronic granulomatous disease.

Umbilical cord blood stem cell transplantation (UCSCT) offers a stem cell source when a

Additionally, the HSC telomere length is longer in patients who have received UCSC than in those who have received PBSC from older donors. UCSCs may have greater self renewing capacity and longevity than those derived from an adult donor. As many transplanted PID patients are infants or young children, giving HSC with a greater proliferative life span is

i. quick access to the cord blood unit and ease of arranging date of transplant

iii. lower risk of latent viral transmission and graft versus host disease (GvHD)


However, the conditioning regimen employed may influence this, as omission of serotherapy enables viral clearance, albeit with an increased risk of GvHD[26].

For PID patients who often present before 1 year of age, UCSCT can offer a suitable stem cell source. In a recent European study mismatched-related donor HSCT was compared to unrelated donor cord HSCT in children with severe T cell deficiencies. There was no significant difference in survival, but cord blood recipients had a higher frequency of complete donor chimerism at day 100 and faster total lymphocyte recovery.[27]

#### **4. Assessment of donor**

A Physician or Paediatrician who is independent to that of the recipient should perform a pre-transplant assessment of any family donor. A medical history should be taken including:


A routine physical examination is performed and a chest radiograph and ECG if indicated.

For unrelated donors the examination is performed by the donor assessment centre. However the transplant centre will need to request blood for confirmatory tissue typing, DNA analysis for post transplant chimerism studies and the opportunity is usually taken to check the donor virology and serology status. The donor's fitness to donate must be ascertained before conditioning of the patient begins. The donor centre is responsible for the consent of the donor. The donor needs to be fully informed about the procedure for collecting the stem cells, the blood tests that will be performed including HIV status, the possibility of a second donation for the same patient and the emphasis on anonymity for the donor and patient. Anonymity may be relaxed in time and regulations may vary in different countries.

For related donors in the UK in addition to a physical examination, under the Human Tissue Act 2004, any potential donation of bone marrow or PBSC from adults who lack capacity to consent and children who lack competence to consent, must be assessed by an Accredited Assessor and a report submitted to the Human Tissue Authority for consideration.

Psychological aspects for the donor are important particularly when children are donating for siblings, for example if the recipient does not survive the donor may feel it is their fault. Therefore preparation and counselling for the donor is important

For cord blood donations at the time of cord collection tests for the following are performed on the mother:

Stem Cell Transplantation for Primary Immunodeficiency 11

With permission from Kath Grey. Liaison team nursing sister. Great North Children's Hospital, Newcastle upon Tyne

A number of infectious agents, particularly viruses, can now be detected by sensitive molecular techniques such as polymerase chain reaction (PCR) at an early stage of the infectious process. This in turn means that pre-emptive therapy can be given before organ damage such as life threatening pneumonitis or hepatitis, occurs. Such early detection together with treatments such as cidofovir for Adenovirus has led to a dramatic

**Figure 2.** Checklist for patients requiring an immunology assessment for HSCT

improvement in outcome following viral infection.

The current minimum serology testing requirements for these products are summarised below:

Anti-HIV-1,2 HBsAg Anti HBc (hepatitis B core antibody) Anti-HCV-Ab (anti-hepatitis C antibody) A validated testing algorithm to exclude the presence of syphilis/active infection with Treponema pallidum (Anti-T. pallidum) HTLV-I antibody testing for maternal donors living in, or originating from, high-incidence areas or with sexual partners originating from those areas, or where the donor's parents originate from those areas.

Furthermore, if the cord blood unit has been stored for more than 180 days the additional testing is required:

Nucleic acid testing for HIV (HIV-NAT) Nucleic acid testing for hepatitis B (HBV-NAT) Nucleic acid testing for hepatitis C (HCV-NAT) Nucleic acid testing for HTLV-I (HTLV-I-NAT) of maternal donors living in, or originating from, high-incidence areas or with sexual partners originating from those areas, or where the donor's parents originate from those areas.

Confirmatory tests 3 to 6 months after delivery are also performed. The health of the baby is also assessed. Cord blood banks will supply the transplant centre with the required viral status of the mother and sometimes the cord blood itself. The cell doses contained within the cord donation and cell viability are also recorded. They will also perform extra tests for confirmatory tissue typing and virology and serology on small aliquots of the cord. Some centres may wish to perform their own confirmatory typing. A small sample is usually taken at the time of thawing for DNA analysis for post transplant chimerism studies.
