Haploidentical Donor T-cell Replete Allogeneic Hematopoietic Cell Transplant Following Reducing Intensity Conditioning for Patients With Selected High Risk Non-Malignant Disease

– Sickle Cell Disease (SCD)

* If diagnosis of SCD must meet one or more of the following disease characteristics:

– Stroke, CNS hemorrhage or a neurologic event lasting longer than 24 hours, or
abnormal cerebral MRI or cerebral arteriogram or MRI angiographic study and
impaired neuropsychological testing

– Acute chest syndrome with a history of recurrent hospitalizations or exchange
transfusions

– Recurrent vaso-occlusive pain 3 or more episodes per year for 3 years or more
years or recurrent priapism,

– Impaired neuropsychological function and abnormal cerebral MRI scan

– Stage I or II sickle lung disease,

– Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration
rate [GFR] 30-50% of the predicted normal value)

– Bilateral proliferative retinopathy and major visual impairment in at least one
eye

– Osteonecrosis of multiple joints with documented destructive changes

– Requirement for chronic transfusions

– RBC alloimmunization

– Transfusion Dependent Alpha- or Beta-Thalassemia

– Other Non-Malignant Hematologic Disorders:

Transfusion dependent or involve other potential life-threatening cytopenias, including but
not limited to Paroxysmal Nocturnal Hemoglobinuria, Glanzmann’s Thrombasthenia, Severe
Congenital Neutropenia and Shwachman-Diamond Syndrome

– cALD

– Diagnosis of ALD by abnormal plasma very long chain fatty acid (VLCFA) profile or
ABCD1 gene mutation

– Cerebral disease on MRI

– Absence of a Major Functional Disability (cortical blindness, loss of
communication, wheelchair dependence) on the ALD Neurologic Function Scale

– Other inherited metabolic disorders:

Any other inherited metabolic disorder for which alloHCT is indicated and for whom, in the
opinion of the treating physician, the patient’s best treatment option is with a
haploidentical donor following non-myeloablatve conditioning.

– Age, Performance Status, Consent

– Age: 0-55 years

– Performance Status: Karnofsky ≥ 70%, Lansky play score ≥ 70

– Consent: voluntary written consent (adult or parental/guardian)

– Adequate Organ Function

– Renal: Creatinine <2.0 mg/dl for adults or glomerular filtration rate > 50 ml/min
for children

– Hepatic: Bilirubin and ALT <3 times the upper limit of institutional normal - Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40%.