All studies to determine eligibility must be performed within 30 days prior to enrollment unless otherwise indicated below. The eligibility criteria listed below are interpreted literally and cannot be waived.
Full study details on Haplo T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease (HaploSCD) Clinical Trial (IND# 14359)
Homozygous Hemoglobin S Disease, or
Hemoglobin β0/+ thalassemia
Patient must be between 2 and 20.99 years of age
Patients must demonstrate one or more of the following
Clinically significant neurologic event (stroke) or any neurologic deficit lasting >24 hours that is accompanied by an infarct on cerebral MRI
Minimum of two episodes of acute chest syndrome
Recurrent painful events (at least 3 in the 2 years prior to enrollment)
Two consecutive abnormal TCD studies (two months apart) with mean velocities in the MCA, ICA, or ACA of > 200 cm/sec requiring chronic transfusion therapy.
Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects), and must sign an informed consent in accordance with the institutional policies approved by the U.S. Department of Health and Human Services.
Approval for the use of this treatment protocol by the individual institution’s Human Rights Committee must be obtained, in accordance with the institutional assurance policies of the U. S. Department of Health and Human Services.
Adequate renal function
Serum creatinine ≤1.5 x upper limit of normal for age, and
Creatinine clearance >60 ml/min/m2 or radioisotope GFR >100 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range.
Adequate liver function
Direct bilirubin <2.0 x upper limit of normal for age as per local laboratory, and
AST or ALT <5.0 x upper limit of normal as per local laboratory
Adequate cardiac function
Shortening fraction ≥27% by echocardiogram, or
Ejection fraction of >40% by echocardiogram.
Adequate pulmonary function
Pulse oximetry ≥85% on room air, and
DLCO >50% (corrected for hemoglobin) in cooperative patients in whom pulmonary function testing can be performed
Performance Status
Karnofsky or Lansky (age appropriate) Performance Score ≥50%
Liver/Iron Overload
For all patients receiving chronic transfusions for ≥1 year and a serum ferritin >1000 ng/ml, a liver biopsy will be performed to assess for iron overload. In all other cases, a liver biopsy is optional
Females who are pregnant or breast-feeding are not eligible
SCD Patients with documented uncontrolled infection at the time of study entry are not eligible
SCD patients who have an unaffected HLA matched family donor willing to proceed to donation or a willing and acceptable 8/8 matched unrelated donor (HLA-A, -B, -C, and –DRB1) eligible for the BMT/CTN SCURT trial will not be eligible for this study.
Karnofsky/Lansky (age appropriate) Performance Score <50% (hemiplegia alone secondary to a previous stroke is not an exclusion)
Demonstrated lack of compliance with medical care
Patients with clinically significant fibrosis or cirrhosis of the liver will not be eligible
Patients who have previously received a HSCT will not be eligible
A familial haploidentical donor without homozygous sickle cell disease (maternal preferred) will be required for study entry.
Must be a first generation relative
Must be 18 years or older
Maternal donors are preferred over paternal or sibling donors
Familial haploidentical donors must have adequate functional status and hematopoietic function defined as
absolute neutrophil count ≥ 1000/mm3
hemoglobin ≥ 9.0 g/dl
platelet count ≥ 50,000/mm3
Karnofsky Performance Score ≥80%
Donors with homozygous Hemoglobin S disease or Hemoglobin S β0/+ thalassemia are ineligible
Familial donors found to have any of the following during infectious disease screening:
HIV I
HIV II
HbsAg
HBc
HCV
CMV
Syphilis
West Nile Virus
HTLV I/II
Donors younger than 18 years old are ineligible to donate