Autologous Tregs for Aplastic Anaemia

Inclusion Criteria:

• Acquired idiopathic AA
• No evidence of constitutional/inherited AA based on clinical findings, absence offamily history of AA, normal DEB test and normal Kings bone marrow failure gene panel
• Very severe, severe or non-severe AA
• Lack a matched sibling donor (MSD) or matched unrelated donor (MUD), or ineligible forMSD/MUD HSCT
• Transfusion dependent
• Failed or ineligible for a course of ATG and CSA
• Failed / intolerant or inappropriate to treat with Eltrombopag or fails to meetBlueteq approval for use of Eltrombopag using NHS England guidance
• AST < 3 x upper limit of normal (ULN), bilirubin < 1.5 x ULN (unless Gilbert'ssyndrome)
• eGFR >50mL/min
• Age ≥ 18 years, male or female
• Willing and able to provide written and informed consent
• If female of child-bearing potential, have a negative serum pregnancy test and agreeto use adequate contraceptive methods if of reproductive age
• Diffusing capacity for carbon monoxide (DLCO) ≥ 45% predicted corrected forhaemoglobin
• LVEF > 40%.
• Performance status ≤ 2

Exclusion Criteria:

• Constitutional AA
• Age < 18 years' old
• Have a MSD and are eligible for MSD HSCT
• Have a MUD and are eligible for MUD HSCT
• Hypocellular myelodysplastic syndrome (Hypo MDS) or AA/Hypo MDS overlap
• Uncontrolled ongoing infection
• Active malignancy
• Treatment of cancer in the last 5 years (except in situ carcinoma of the cervix orbasal cell carcinoma)
• Unable to give informed consent
• Active or uncontrolled infection not responding to appropriate antibiotics andantifungal agents.
• Human immunodeficiency virus (HIV) sero-positivity, hepatitis B, hepatitis C orhepatitis E infection.
• Abnormal organ function: AST/ALT >3 x upper limit of normal (ULN), bilirubin >1.5 xULN, eGFR ≤50mL/min
• Heart failure (= grade III New York Heart Association)
• Pregnant or lactating women
• Unable or unwilling to comply with the contraceptive requirements