RElated Haplo-DonoR Haematopoietic stEm Cell Transplantation for Adults With Severe Sickle Cell Disease

Korábbi kezelés

• Previous bone marrow transplant.
• Clinically significant donor specific HLA antibodies.

Más betegség

• HIV infection or active Hepatitis B or C.
• Uncontrolled infection including bacterial, fungal and viral.
• Pre-existing condition deemed to significantly increase the risk of Haploidentical SCT by the local Principal Investigator.

Egyéb

• Fully matched sibling donor.
• Pregnancy or breast feeding.
• Participants able to conceive a child that are unprepared to use effective contraception.
• Participation in another interventional trial in the last three months.

• Adult patients age ≥ 18 years
• Confirmed haploidentical donor
• Severe SCD phenotype who are at high risk for morbidity and mortality. Severe SCD is defined by at least one of the following:
• Clinically significant neurologic event (stroke) or deficit lasting > 24 hours.
• History of ≥2 acute chest syndromes in a 2-year period preceding enrolment despite optimum treatment, e.g. with hydroxycarbamide (HC).
• History of ≥3 severe pain crises per year in a 2-year period preceding enrolment despite the institution of supportive care measures (e.g. optimum treatment with HC).
• Administration of regular transfusion therapy (=8 packed red blood transfusions per year for 1 year to prevent vaso-occlusive complications).
• Patients assessed as requiring transfusion but with red cell allo-antibodies/very rare blood type, rendering it difficult to continue/commence chronic transfusion.
• Patients requiring HC/transfusion for treatment of SCD complications who cannot tolerate either therapy due to significant adverse reactions.
• Established end organ damage relating to SCD, including but not limited to progressive sickle vasculopathy and hepatopathy. End-organ sufficient for entry to this trial shall be ratified at the UK NHP.
• Patients must be fit to proceed to Haploidentical SCT as defined below: i. Karnofsky score ≥60 ii. Cardiac function: LVEF ≥45% or shortening fraction ≥25% iii. Lung Function: FEV1, FVC and TLCO ≥50% iv. Renal function: EDTA GFR ≥40 ml/min/1.73m2 v. Hepatic function: ALT <x3 ULN and bilirubin <x2 the upper limit of normal, those with hyperbilirubinemia due to sickle related haemolysis will not be excluded. No radiological evidence of cirrhosis.
• Written informed consent.