Stem Cell Transplantation for Sickle Cell Anemia
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Intervention: Alemtuzumab; Fludarabine; Melphalan; Stem Cells
Intervention description: Adjusted Ideal Body Weight Formula: AIBW = IBW + [(0.4) x (ABW - IBW)]
b) Medications
i.) Alemtuzumab I. Hb S% must be < or = 45% within 7 days prior to initiation of Alemtuzumab II. Iron chelation and hydroxyurea must be discontinued >48 hours before initiating therapy III. Alemtuzumab will be diluted in 100mL of 0.9% NS and infused at a rate as below; I. Fludarabine should be diluted in 100 ml 0.9%NS and given over 30 minutes. II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Fludarabine; I. Melphalan should be diluted in 0.9%NS to a concentration of 0.1 -0.45 mg/mL and given over 45 minutes. *Entire dose must be infused within 60 minutes of reconstitution in Pharmacy.
II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Melphalan III. Patients should be encouraged to suck on a popsicle or something similar during the Melphalan infusion.; Infusion of Hematopoietic Stem Cells
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Melphalan; Alemtuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 2 Years
Maximum age: 30 Years
Healthy volunteers: No
Keywords: Stem cell transplant; Sickle cell; Stem cell transplantation; Related; Unrelated

Summary:

      This protocol will be investigating the use of stem cell transplantation, in related donors,
      to cure sickle cell disease. Sickle cell disease is a recessive disorder caused by a point
      mutation that results in the substitution of valine for glutamic acid at the sixth position
      in the B-chain of hemoglobin. This leads to sickling of the red blood cells under many
      conditions, such as hypoxia, dehydration, and hyperthermia. The sickling leads to
      vaso-occlusion, which causes irreversible damage in almost all systems in the body, including
      the central nervous system (CNS), lungs, heart, bones, eyes, liver, and kidneys.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient Eligibility

             1) Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single or double) with a
             total TNC dose of greater than 5 x 107/kg recipient weight)

               1. Age 2-30

               2. Hb SS, S-thal0, S-thal+, SC

               3. Evidence of ongoing hemolysis: Hb<10, retic >5%, LDH > 500, TB>2

               4. Karnofsky/Lansky score >50

               5. LVSF>26% or LVEF>40%

               6. DLCO >40% or O2 sat >85% for those patients that can't perform PFTs

               7. GFR >70 and serum creatinine < 1.5 * ULN for age

               8. ALT and AST < 5 x ULN, direct bilirubin <2 x ULN

               9. If the patient has been on chronic transfusion or has a ferritin >1000, liver
                  biopsy should be done and show no evidence of bridging fibrosis or cirrhosis

          -  Exclusion criteria

               1. Evidence of uncontrolled bacterial, viral, or fungal infection within one month
                  prior to initiation of the conditioning regimen

               2. Pregnant or breastfeeding

               3. HIV positive

               4. Written informed consent not obtained