Eligibility criteria
| Clinical severity . | Physical function . |
|---|---|
| Clinically significant neurologic event (stroke) or neurological deficit lasting >24 h. | Karnofsky/Lansky performance score ≥60; left ventricular ejection fraction >40% or left ventricular shortening fraction >26% by cardiac echocardiogram or multigated acquisition (MUGA) scan. |
| History of 2 or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment or referral, despite adequate supportive care measures, such as asthma therapy. | Pulse oximetry with baseline O2 saturation of ≥85% and lung diffusion test (DLCO) > 40%, corrected for hemoglobin. |
| An average of 3 or more pain crises per year in the 2-y period preceding enrollment or referral that required IV pain management in the outpatient or inpatient hospital setting. | Serum creatinine ≤1.5 × upper limit of normal (ULN) per local laboratory and either creatine clearance >70 mL/min using Cockcroft-Gault calculation or creatinine clearance >70 mL/min by 24-h urine or glomerular filtration rate (GFR) >70 mL/min per 1.73 m2 by radionuclide GFR; ALT and AST <5 × ULN. |
| Administration of regular red blood cell (RBC) transfusion therapy, defined as 8 or more transfusion events per year (in the 12 months before enrollment) to prevent vaso-occlusive clinical complications, such as pain, stroke, or ACS. | Serum conjugated bilirubin ≤2 × ULN for age per local laboratory (serum conjugated bilirubin >2 × ULN permitted if there is evidence of hyper hemolytic reaction after recent RBC transfusion or moderate direct hyperbilirubinemia (direct serum bilirubin <5 times ULN and not caused by underlying hepatic disease). |
| An echocardiographic finding of tricuspid valve regurgitant jet velocity ≥2.7 m/s. | |
| Ongoing high impact chronic pain on a majority of days per month for ≥6 months as defined by 1 or more of the following: chronic pain without contributory SCD complications OR mixed pain type in which chronic pain is occurring at sites unrelated to any sites associated with contributory SCD complications, such as leg ulcers and/or avascular necrosis. | |
| Participants assigned to the donor arm were required to meet the following additional criteria to proceed with HCT before start of conditioning: | |
| Liver MRI to document hepatic iron content if participant was currently receiving ≥8 packed RBC transfusions for 1 or more years or had received a cumulative total of ≥20 packed RBC transfusions. Participants with hepatic iron content ≥7 mg Fe/g liver dry weight by liver MRI were required to have a liver biopsy and histologic examination to document the absence of cirrhosis, bridging fibrosis, and active hepatitis. | |
| Lack of clinical or radiologic evidence of a recent neurologic event by cerebral MRI/MRA. | |
| Documentation of willingness to use approve contraception until discontinuation of all immunosuppressive medications. | |
| Clinical severity . | Physical function . |
|---|---|
| Clinically significant neurologic event (stroke) or neurological deficit lasting >24 h. | Karnofsky/Lansky performance score ≥60; left ventricular ejection fraction >40% or left ventricular shortening fraction >26% by cardiac echocardiogram or multigated acquisition (MUGA) scan. |
| History of 2 or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment or referral, despite adequate supportive care measures, such as asthma therapy. | Pulse oximetry with baseline O2 saturation of ≥85% and lung diffusion test (DLCO) > 40%, corrected for hemoglobin. |
| An average of 3 or more pain crises per year in the 2-y period preceding enrollment or referral that required IV pain management in the outpatient or inpatient hospital setting. | Serum creatinine ≤1.5 × upper limit of normal (ULN) per local laboratory and either creatine clearance >70 mL/min using Cockcroft-Gault calculation or creatinine clearance >70 mL/min by 24-h urine or glomerular filtration rate (GFR) >70 mL/min per 1.73 m2 by radionuclide GFR; ALT and AST <5 × ULN. |
| Administration of regular red blood cell (RBC) transfusion therapy, defined as 8 or more transfusion events per year (in the 12 months before enrollment) to prevent vaso-occlusive clinical complications, such as pain, stroke, or ACS. | Serum conjugated bilirubin ≤2 × ULN for age per local laboratory (serum conjugated bilirubin >2 × ULN permitted if there is evidence of hyper hemolytic reaction after recent RBC transfusion or moderate direct hyperbilirubinemia (direct serum bilirubin <5 times ULN and not caused by underlying hepatic disease). |
| An echocardiographic finding of tricuspid valve regurgitant jet velocity ≥2.7 m/s. | |
| Ongoing high impact chronic pain on a majority of days per month for ≥6 months as defined by 1 or more of the following: chronic pain without contributory SCD complications OR mixed pain type in which chronic pain is occurring at sites unrelated to any sites associated with contributory SCD complications, such as leg ulcers and/or avascular necrosis. | |
| Participants assigned to the donor arm were required to meet the following additional criteria to proceed with HCT before start of conditioning: | |
| Liver MRI to document hepatic iron content if participant was currently receiving ≥8 packed RBC transfusions for 1 or more years or had received a cumulative total of ≥20 packed RBC transfusions. Participants with hepatic iron content ≥7 mg Fe/g liver dry weight by liver MRI were required to have a liver biopsy and histologic examination to document the absence of cirrhosis, bridging fibrosis, and active hepatitis. | |
| Lack of clinical or radiologic evidence of a recent neurologic event by cerebral MRI/MRA. | |
| Documentation of willingness to use approve contraception until discontinuation of all immunosuppressive medications. | |
Individuals with a previous HLA typing of both related and unrelated potential donors were not eligible for this study. Those who only had previous HLA typing performed on family members, without identifying a matched related donor and with no extension of HLA-typing to potential unrelated donors, were eligible for this study.
MRA, magnetic resonance angiogram; MRI, magenetic resonance imaging.