Stem Cell and Bone Marrow Transplants

This page is to provide information to healthcare professionals about stem cell and bone marrow transplants

Sibling allograft 

Inclusion and Exclusion Criteria

Other than having a fully matched sibling, patients who meet any one of the following criteria could be considered for HPCT:

• Clinically significant neurological vascular event or deficit lasting >24 hrs and confirmed radiologically.
• History of ≥2 acute chest syndrome despite optimum treatment with hydroxycarbamide (HC) or transfusion therapy.
• History of ≥3 severe pain crises or other acute complications per year despite the institution of supportive care measures (optimum treatment with HC or transfusion therapy). Other acute complications would include acute hepatopathy, splenic sequestration or acute priapism.
• Enrolment onto transfusion programme, either by simple transfusion or exchange transfusion with the aim to prevent severe sickle complications by maintaining a low HbS%.
• 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 sickle cell disease complications who cannot tolerate either therapy due to significant adverse reactions.
• Established and related end organ damage due to sickle cell disease, including but not limited to progressive sickle neurovasculopathy and hepatopathy.

 

To determine fitness to proceed to HPCT, patients should have all of the following:

1. Karnofsky score ≥60

2. Cardiac function: LVEF >45% or shortening fraction ≥25%.

• Note: For subjects who have history of iron overload or serum ferritin levels >1000 µg/L, a cardiac MRI is required. Cardiac T2* <10 ms results in exclusion.
  
  

3. Lung Function: FEV1, FVC and DLCO ≥50%

4. Renal function: EDTA GFR ≥40 ml/m2/1.73m2

 

REDRESS (haploidentical transplant)

INCLUSION CRITERIA

a) Adult patients age ≥ 18 years

b) Confirmed haploidentical donor

c) Severe SCD phenotype who are at high risk for morbidity and mortality. Severe SCD is defined by at least one of the following:

i. 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

a) Fully matched sibling donor.

b) Previous bone marrow transplant.

c) Pregnancy or breast feeding.

d) Participants able to conceive a child that are unprepared to use effective contraception.

e) Clinically significant donor specific HLA antibodies.


f) HIV infection or active Hepatitis B or C.

g) Uncontrolled infection including bacterial, fungal and viral.

h) Participation in another interventional trial in the last three months.

i) Pre-existing condition deemed to significantly increase the risk of Haploidentical SCT by the local Principal Investigator.