Stem Cell Transplant in Sickle Cell Disease and Thalassemia

Sickle cell disease is a genetic disorder in which a mutation in the beta chain of human
hemoglobin results in abnormal blood hemoglobin, causing red blood cells to sickle under
stress with resulting symptoms including severe pains and strokes. Beta thalassemia is
another genetic disorder in which there are abnormal beta hemoglobin chains, causing anemia.
In both disorders, frequent red blood cell transfusions may be required to sustain life, but
these often result in complications including multiple hospitalizations, iron overload, or
bacterial or viral infections such as hepatitis. Standard drugs and therapies used in the
treatment of sickle cell disease and/or beta thalassemia provide only supportive care, and
may result in long-term side effects, and inadequate control of the disease process. Bone
marrow transplant has been increasingly used for the long-term treatment and cure of sickle
cell disease and beta thalassemia. Although, not without acute and potential long term side
effects, this alternative offers long term control and potential cure of the disease. Most of
the side effects seen with bone marrow transplant are directly related to the high intensity
of chemotherapy used (ablative).

Inclusion Criteria:

Sickle Cell Disease:

- Diagnosis of Homozygous Hemoglobin S Disease or Heterozygous Hemoglobin Sickle Cell
(SC) or S 0/+ thalassemia, or Sickle/variant resulting in Chronic Hemolytic Anemia
with hemoglobin (HgB) ≤10 mg/dL

- Age ≤30

- Matched sibling donor and asymptomatic, or 8/8 human leukocyte antigen (HLA) matched
unrelated adult donor

Patient must have adequate organ function as below:

- Adequate renal function defined as serum creatinine ≤1.5 x normal, or Creatinine
clearance or radioisotope glomerular filtration rate (GFR) >100 ml/min/1.73 m2 or
>70ml/min/1.73m2 for patients >16 years old

- Adequate liver function defined as serum glutamic oxaloacetic transaminase (SGOT)
(aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SGPT)
(alanine aminotransferase (ALT)) < 5.0 x normal

- Adequate Cardiac Function defined as shortening fraction of ≥28% by echocardiogram, or
ejection fraction of ≥48% by radionuclide angiogram or echocardiogram

- Adequate pulmonary function defined as corrected Diffusing capacity of the lungs for
carbon monoxide (DLCO) ≥40% by pulmonary function test, or for children who are unable
to perform DLCO maneuver ≥85% O2 saturation, no evidence of dyspnea at rest

Exclusion criteria:

General

- Karnofsky/Lansky Performance Score <60%

- Demonstrated lack of compliance with medical care

- Pregnant or nursing

- Evidence of uncontrolled bacterial, viral or fungal infections (currently taking
medication and progression of clinical symptoms) within 1 month prior to starting the
conditioning regimen. Patients with fever or suspected minor infection should await
resolution of symptoms before starting the conditioning regimen.

Histologic Exam of Liver (liver biopsy) with bridging fibrosis or cirrhosis.