|Akshay Sharma, MBBS|
1 United States site
2 to 25 Years
for Transplant Recipient
Age less than or equal to 25 years.
Patients with a suitable HLA-matched sibling donor (MSD) can be enrolled on MSD arm of the trial. Patients with single haplotype matched (≥ 3 of 6) family member donor can be enrolled on HAPLO arm of the trial, if they do not have a suitable HLA-matched sibling donor (MSD) available for progenitor cell donation.
Patients with SCD (any genotype) who meet any ONE of the following criteria:
History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥ 200 cm/sec by the non-imaging technique (or ≥ 185 cm/sec by the imaging technique) measured at a minimum of two separate occasions.
History of cerebral infarction on brain MRI (overt stroke, or silent stroke if ≥3 mm in one dimension, visible in two planes on fluid-attenuated inversion recovery T2- weighted images).
History of two or more episodes of acute chest syndrome (ACS) in the 2-years period preceding enrollment.
History of two or more SCD pain events requiring treatment with an opiate or IV pain medication (inpatient or outpatient) in the last 12 months.
History of any hospitalization for SCD pain or ACS while receiving hydroxyurea treatment in the last 12 months.
History of two or more episodes of priapism (erection lasting ≥4 hours or requiring emergent medical care).
Administration of regular RBC transfusions (≥8 transfusions in the previous 12 months).
At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration.
for Transplant Recipient
Karnofsky or Lansky performance score <60.
Pregnant or breastfeeding patients.
Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning. Patients with confirmed seropositivity or positive NAAT for HIV are excluded.
Serum conjugated (direct) bilirubin >3x upper limit of normal for age or serum ALT >5x upper limit of normal for age as per local laboratory. Participants with hyperbilirubinemia or elevated AST as the result of hyperhemolysis, or a severe drop in hemoglobin post blood transfusion, are not excluded as long as these values downtrend and return to acceptable limits subsequently.
Left ventricular shortening fraction <25% or ejection fraction <40% by echocardiogram. Estimated creatinine clearance less than 50 mL/min/1.73m2. Diffusion capacity of carbon monoxide (DLCO) <35% (adjusted for hemoglobin). Baseline oxygen saturation <85% or PaO2 <70. History of RBC alloantibodies against donor RBC antigens (even if current antibody screen is negative). Presence of high titer anti-donor specific HLA antibodies should be carefully evaluated, and desensitization considered prior to transplantation. HLA antibody presence and specificity will be determined by solid phase immunoassays. An anti-donor specific HLA antibody will be considered positive when the mean fluorescence intensity (MFI) is >1000 for donor specific antibody to HLA-A, -B, and DRB1 and MFI >2000 for HLA-C, DQB1 and DPB1. Patients with borderline elevated anti-donor specific HLA antibodies may be considered for inclusion in consultation with the PIs.