Transplant Recipient - Age less than or equal to 22 years. - Patients without a suitable HLA-matched sibling donor but with a suitable single haplotype matched (≥ 3 of 6) family member donor. Potential donors do not need to undergo eligibility determination prior to the recipients enrolling on the study. As long as a potential donor is identified and willing to donate hematopoietic progenitor cells, recipients can enroll on the study. - 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 cerebral infarct). - History of two or more episodes of acute chest syndrome (ACS) in the 2-years period preceding enrollment. - History of two or more SCD related pain events requiring treatment with parenteral analgesics 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). - Evidence of progressive end organ damage (eg. cardiomyopathy, nephropathy, pulmonary hypertension etc) that in the opinion of the treating hematologist is not responsive to medical management and may benefit from an HCT. Such a determination must be made in writing by at least two independent hematologists and documented in the patient's electronic medical record prior to enrollment. Donor - An at least single haplotype matched (≥ 3 of 6) family member. - HIV negative - Not pregnant, as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female). - Not breast feeding. - Donor should not have clinically significant hemoglobinopathy. Donors with sickle cell trait are acceptable. - Regarding donation eligibility, is identified as either: - Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR. - Does not meet 21 CFR 1271 eligibility requirements but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271.

Transplant Recipient - Karnofsky or Lansky performance score <60. - Pregnant, as confirmed by positive serum or urine pregnancy test within 14 days prior to enrollment (if female). - Breast feeding. - 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 as per local laboratory. Participants with hyperbilirubinemia as the result of hyperhemolysis, or a severe drop in hemoglobin post blood transfusion, are not excluded as long as it downtrends 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) OR baseline oxygen saturation <85% or PaO2 <70. - Presence of anti-donor specific HLA antibodies unresponsive to desensitization.