Stem Cell Transplantation for Sickle Cell Anemia

Primary objective:

1) To determine disease free survival (DFS) at one year after matched sibling transplant
using either bone marrow (BM), peripheral blood stem cells (PBSC), or umbilical cord blood
(UCB) after a conditioning regimen consisting of Alemtuzumab, Fludarabine, and Melphalan in
patients 2-30 y/o

Secondary objectives:

1. Overall survival

2. Rate of neutrophil and platelet engraftment for BM vs. UCB

3. Incidence of graft failure

4. Incidence of grade II-IV and grade III-IV acute graft vs host disease (GVHD)

5. Incidence of chronic GVHD

6. Incidence of other transplant complications, such as veno-occlusive disease, central
nervous system (CNS) toxicity, and idiopathic pneumonia syndrome (IPS)

7. Incidence of reactivation of CMV, EBV, adenovirus, BK/JC virus

8. Incidence of invasive fungal disease

9. Time to immune reconstitution via monitoring of lymphocyte subpopulations and
immunoglobulin levels

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