131I-apamistamab-based Conditioning for Hematopoietic Stem Cell Transplant (HSCT) in Advanced Sickle Cell Disease (SCD)

Inclusion Criteria: * Availability of an HLA-matched sibling donor * Patients with sickle cell anemia (Hb SS, Sβ0 thalassemia or severe SC) who are 12 - 50 years of age inclusive AND who have 1 or more of the following: 1. Clinically significant neurologic event (stroke) or any neurological deficit lasting at least 24 hours. Stroke will be defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI or cerebral arteriopathy requiring chronic transfusion therapy. 2. History of two or more episodes of ACS in the 2-year period preceding enrollment despite supportive care measures (i.e. asthma therapy and/or hydroxyurea). 3. History of three or more severe vaso-occlusive pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea). 4. Administration of regular RBC transfusion therapy, defined as receiving 8 or more transfusions per year for 1 year or more to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and ACS) 5. An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity \> or equal to 2.7 m/sec or pulmonary hypertension diagnosed by right heart catherization. 6. Sickle hepatopathy defined as EITHER ferritin \>1000mcg/L OR direct bilirubin \>0.4mg/dl but \<5xULN AND platelet count \<250,000/uL at baseline * Adequate organ functions as defined as: 1. ECOG performance status of 2 or better 2. Cardiac function: LVEF of 40% or greater 3. Pulmonary Function: Pulse oximetry with a baseline oxygen saturation of 85% or greater and corrected DLCO of 40% or greater 4. Hepatic Function: Serum conjugated (direct) bilirubin less than 5x upper limit of normal for age as per local laboratory, ALT and AST less than 5 x upper limit of normal as per local laboratory. Patients whose hyperbilirubinemia is the result of hyperhaemolysis, or a sever drop in hemoglobin post blood transfusion are not excluded. 5. Absence of liver cirrhosis, bridging fibrosis and active hepatitis as documented by liver biopsy for patients with evidence of iron overload by serum ferritin or MRI. The histological grading and scale described by Ishak and colleagues (1995) will be used. Donor Eligibility and Selection Criteria 1. Donor should be evaluated for eligibility to donate by an independent physician not directly caring for the patient on study protocol. 2. Donor is willing to sign informed consent allowing the use of the PBSC product for the HSCT of the recipient. 3. Donor cannot be pregnant or lactating and must agree to contraception until after the donation procedure is complete. 4. Testing negative for HIV and viral hepatitis 5. Free of Hb S (defined as Hb S less than 50%) and other hemoglobinopathies that are symptomatic or of clinical significance. 6. Targeted minimum stem cell dose of 5.0 x 10e6 CD34 cells/Kg of recipient weight 7. Fulfills standard criteria for eligibility as a donor for HSCT. Note: HSCT can be deleterious for the developing fetus and pregnant mother due to the conditioning regimen, GVHD prophylaxis and treatment. Agents used in this study such as cyclophosphamide are pregnancy risk factor category D. Sirolimus is pregnancy risk factor category C. Radiotherapy also used (TBI) is a well-known teratogenic agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for at least 1 year post transplant. Finally, pregnancy and lactation restrictions and contraception requirements are also applicable to the donor. Filgrastim or other G-CSF analogous are pregnancy risk factor category C. The restriction lasts for 4 weeks after stem cell donation. Exclusion Criteria: 1. Pulmonary dysfunction defined as DLCO (corrected for hemoglobin and alveolar volume) \< 40% of predicted OR baseline oxygen saturation of \<85% or PaO2 \<70. 2. Severe cardiac dysfunction defined as ejection fraction \<35%. 3. Impaired renal function defined as GFR \<40. 4. Hepatic dysfunction defined as bridging (portal to portal) fibrosis or cirrhosis of the liver OR transaminases \>5x ULN for age. 5. Clinical stroke within 6 months of anticipated transplant 6. Karnofsky performance score \< 50% 7. HIV infection 8. Uncontrolled viral, bacterial, fungal, or protozoal infection at the time of study enrollment. 9. Have circulating HAMA noted on initial screening. 10. Have received prior radiation to maximally tolerated levels to any critical normal organs 11. Patients with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate HSCT. 12. Patients' unable to understand the nature and risks inherent in the HSCT process. 13. History of non-compliance severe enough in the estimation of the treating team to preclude the patient from undergoing unrelated donor transplantation. 14. Patient is pregnant or lactating. 15. Inability to provide adequate transfusion support or increased risk immunohematological complications due presence of anti-RBC antibody against stem cell donor. 16. Patients with any history of radiation therapy.