Patient description: The patient is a 34-year-old African American man with the known history of Sickle cell disease comes to the clinic with severe bone pain. The patient had severe pain in his lower back that radiated to both thighs scored 9 out of 10. The patient has had positive history of sickle cell crises since childhood. He also had the same symptoms in past two weeks treated with oxycodone which was not beneficial to his pain. His PCP sent him to the emergency department to receive intra venous pain modulators. The patient is afebrile within the normal blood pressure. No splenomegaly was detected in the physical exam. He has no positive history of drug allergy. He won't smoke or uses any illicit drugs. The lab study is as bellow: Hgb: 8 g/dl WBC: 10000 /mm3 Plt: 300000 /ml MCV: 106 fL Hemoglobine electrophoresis: 91% HbS 6%HbF 3%HbA2 AST: 22 U/L ALT: 43 U/L Alk P: 53 U/L Ferritin: 1200 ng/ml

Clinical trial eligibility criteria: eligible ages (years): 18.0-45.0,  Sickle Cell Disease and Thalassemia Recipient Disease specific: Sickle Cell Disease Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having irreversible end-organ damage (A, B, C,D, or E) or potentially reversible complication(s) not ameliorated by hydroxyurea (F): A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI OR an abnormal trans-cranial Doppler examination (≥200m/s); OR B. 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 < 50mL/min OR requiring peritoneal or hemodialysis. OR C. Pulmonary hypertension as defined by tricuspid regurgitant jet velocity (TRV) of ≥ 2.5m/s at least 3 weeks after a vaso-occlusive crisis; OR D. Recurrent tricorporal priapism defined as at least two episodes of an erection lasting ≥4 hours involving the corpora cavernosa and corpus spongiosa; OR E. Sickle hepatopathy defined as ferritin >1000mcg/L OR direct bilirubin >0.4 mg/dL at baseline; OR F. Any one of the below complications 1. Vaso-occlusive crises 2. Acute chest syndrome 3. Osteonecrosis of 2 or more joints 4. Red cell alloimmunization Thalassemia Patients with 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 desferroxamine initiated within 18 months of the first transfusion and administered subcutaneously for 8-10 hours at least 5 days each week) hepatomegaly of greater than 2 cm below the costochondral margin Non-disease specific: Ages ≥ 18 but ≤ 45 6/6 HLA matched family donor available Ability to comprehend and willing to sign an informed consent, assent obtained from minors Negative serum pregnancy test Donor 6/6 HLA identical family donor Weight > 20 kg (in so far that the weight difference between recipient and donor does not exceed a reasonable likelihood of being able to obtain an adequate cell dose from the donor within two aphereses) Fit to receive G-CSF and give peripheral blood stem cells (normal blood counts, normotensive, and no history of stroke) Ability to comprehend and willing to sign an informed consent  Recipient Any of the following would the subject from participating ECOG performance status of 3 or more or Lanksy performance status of <40 Diffusion capacity of carbon monoxide (DLCO) <50% predicted (corrected for hemoglobin and alveolar volume) Baseline oxygen saturation of <85% or PaO2 <70 Left ventricular ejection fraction: <40% 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 PBSC transplant Pregnant or lactating Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) Major ABO mismatch Donor Any of the following would the donor from participating Pregnant or lactating Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months) HIV positive Hemoglobin S > 50%, or beta thalassemia intermediate