Partial Stem Cell Transplant for Sickle Cell Disease From Matched Donors

* INCLUSION CRITERIA RECIPIENT: Participants must fulfill one disease category (1 or 2) and 3 1. Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having an end-organ damage (A, B, C, D, OR E) or complication(s) not ameliorated by sickle cell-specific therapies (F): A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI ORb B. Abnormal trans-cranial Doppler examination (\>=200 cm/s); OR C. Silent cerebral infarct defined as an infarct-like lesion based on an MRI signal abnormality at least 3 mm in one dimension and visible in two planes on FLAIR or T2- weighted images (or similar image with 3D imaging) and documented neurological examination performed by a neurologist demonstrating the participant has a normal neurologic examination, or an abnormality on examination that could not be explained by the location of the brain lesion(s); OR D. Sickle cell related renal insufficiency defined by a creatinine level \>=1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance \<60mL/min/1.73m2 for patients \<16 years of age or \<50mL/min for patients \>16 years of age OR requiring peritoneal or hemodialysis; OR Age (Years): \<= 5 / Upper limit of normal serum creatinine (mg/dl): 0.8 Age (Years): 5 \< age \<= 10 / Upper limit of normal serum creatinine (mg/dl): 1.0 Age (Years): 10 \< age \<= 15 / Upper limit of normal serum creatinine (mg/dl): 1.2 Age (Years): \> 15 / Upper limit of normal serum creatinine (mg/dl): 1.3 E. Tricuspid regurgitant jet velocity (TRV) of \>=2.5 m/s in patients at least 3 weeks after a vaso-occlusive crisis; OR F. Recurrent severe priapism defined as at least two episodes of an erection lasting \>=4 hours requiring medical intervention (e.g. aspiration, injection of vasoconstrictor, prior penile surgery.); OR G. Sickle hepatopathy defined as EITHER ferritin \>1000mcg/L OR direct bilirubin \>0.4 mg/dL at baseline; OR H. Vaso-occlusive crises: more than 1 hospital admission per year while on a therapeutic dose of sickle cell treatment /medication; OR I. Acute chest syndrome (ACS): any ACS while on sickle cell treatment /medication 2. Patients with beta-thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following: * Portal fibrosis by liver biopsy * Inadequate chelation history (defined as failure to maintain adequate compliance with chelation with deferoxamine initiated within 18 months of the first transfusion and administered at least 5 days each week) * Hepatomegaly of greater than 2 cm below the costochondral margin or by other imaging scans 3. Non disease specific * Ages \>=4 years and less than 65 years old * Fully matched human leukocyte antigen (HLA) donors at A, B, C, and DR loci (8 of 8 or 10 of 10) * Ability to comprehend and willing to sign an informed consent, assent obtained from minors when applicable. Negative serum or urine beta-HCG, when applicable * Agree to use birth control throughout the study and 3 months after abatacept or sirolimus administration. * Female subjects must agree to use a medically acceptable method of birth control such as oral contraceptive, intrauterine device, barrier and spermicide, or implant/injection from start of screening until immunosuppression is stopped. * Male subjects must agree to use effective contraception (including condoms) from start of screening until immunosuppression is stopped. DONOR: * Fully matched human leukocyte antigen (HLA) donors at A, B, C, and DR loci (8 of 8 or 10 of 10) are intended for this study. * Donors age 4 or older and \>=15 kg (or weight deemed acceptable by IR for line placement, DTM for apheresis, and pediatric consult service) eligible to donate hematopoietic stem cells, are eligible for this study. * Donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Donors will sign on a separate protocol, 20-H-0099 NHLBI standard of care protocol for the mobilization and collection of HSCs. Note that participation in this study is offered to all eligible donors, but is not required for a donor to make a stem cell donation, so it is possible that not all donors will enroll onto this study. EXCLUSION CRITERIA RECIPIENT: * Karnofsky or Lanksy performance status of \<40 * Diffusing capacity of carbon monoxide \<35% predicted: DLCO corrected for hemoglobin or KCO (corrected for lung volume). This criterion may be omitted in young children (e.g. near age 5) or other individuals who may have difficulty understanding or complying with instructions of testing. * Baseline oxygen saturation of \<85% or PaO2 \<70 * Left ventricular ejection fraction: \<35% estimated by ECHO * Transaminases \>5x upper limit of normal for age * Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to starting the conditioning regimen * Major anticipated illness or organ failure incompatible with survival from HCT * Pregnant or breastfeeding DONOR: * Pregnant or breastfeeding * Cognitively impaired subjects