Overview

The purpose of this clinical trial is to evaluate the clinical and cost effectiveness of Haploidentical Stem Cell Transplantation (SCT) for adults with severe sickle cell disease (SCD), who have failed other therapies or are intolerant of existing therapies or require chronic transfusions to prevent on-going complications of SCD.

Eligibility

Inclusion Criteria:

1. Adult patients age ≥ 18 years
2. Confirmed haploidentical donor
3. Severe SCD phenotype who are at high risk for morbidity and mortality. Severe SCD is defined by at least one of the following:
4. Clinically significant neurologic event (stroke) or deficit lasting > 24 hours.

        ii. History of ≥2 acute chest syndromes in a 2-year period preceding enrolment despite
        optimum treatment, e.g. with hydroxycarbamide (HC).
        iii. 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).
        iv. Administration of regular transfusion therapy (=8 packed red blood transfusions per
        year for 1 year to prevent vaso-occlusive complications).
        v. Patients assessed as requiring transfusion but with red cell allo-antibodies/very rare
        blood type, rendering it difficult to continue/commence chronic transfusion.
        vi. Patients requiring HC/transfusion for treatment of SCD complications who cannot
        tolerate either therapy due to significant adverse reactions.
        vii. 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.
        d) 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.
        e) Written informed consent.
        Exclusion Criteria:
          1. Fully matched sibling donor.
          2. Previous bone marrow transplant.
          3. Pregnancy or breast feeding.
          4. Participants able to conceive a child that are unprepared to use effective
             contraception.
          5. Clinically significant donor specific HLA antibodies.
          6. HIV infection or active Hepatitis B or C.
          7. Uncontrolled infection including bacterial, fungal and viral.
          8. Participation in another interventional trial in the last three months.
          9. Pre-existing condition deemed to significantly increase the risk of Haploidentical SCT
             by the local Principal Investigator.