Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease
Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease
The study is a Phase II clinical trial. Patients will receive intensity modulated total body
 irradiation (TBI) at a dose of 3 Gy with standard fludarabine/ i.v. cyclophosphamide
 conditioning prior to human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell
 transplant (HSCT).

 The primary objective of the study is to determine the engraftment at Day +60 following
 HLA-haploidentical hematopoietic stem cell transplant protocol using immunosuppressive agents
 and low-dose total body irradiation (TBI) for conditioning and post-transplant
 cyclophosphamide in patients with sickle cell disease.
Patient Eligibility:

 1. Patients with sickle cell disease are eligible if they have any of the following
 complications:

 1.1 Stroke or central nervous system event lasting longer than 24 hours 1.2 Frequent
 vaso-occlusive pain episodes, defined as ≥ 3 per year requiring emergency room, acute
 care center, hospital admissions, or home bedrest leading to absence from work or
 school. 1.3 Recurrent episodes of priapism, defined as ≥ 2 per year requiring
 emergency room visits 1.4 Acute chest syndrome with recurrent hospitalizations,
 defined as ≥ 2 lifetime events 1.5 Red-cell alloimmunization (≥ 2 antibodies) during
 long-term transfusion therapy 1.6 Bilateral proliferative retinopathy with major
 visual impairment in at least one eye 1.7 Osteonecrosis of 2 or more joints 1.8 Sickle
 cell nephropathy, defined by a GFR < 90mL/min/1.73m2 or the presence of
 macroalbuminuria (urine albumin > 300 mg/g creatinine) 1.9 Pulmonary hypertension,
 defined by a mean pulmonary arterypressure >25mmHg

 2. Age 16-60 years

 3. Karnofsky performance status of 60 or higher (Appendix A)

 4. Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40%

 5. Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥
 50% predicted (after adjustment for hemoglobin concentration)

 6. Estimated GFR ≥ 50mL/min/1.73m2 as calculated by the modified MDRD equation

 7. ALT ≤ 3x upper limit of normal

 8. HIV-negative

 9. Patient is not pregnant

 10. Patient is able and willing to sign informed consent

 11. Patient does not have a fully HLA-matched sibling donor

 12. Patient has an HLA-haploidentical relative

 Donor Eligibility Relatives (parents, offspring, siblings, aunts/uncles, cousins) will be
 tested by molecular typing of HLA class I (A, B, and C) and class II (DRB1) at low
 resolution. Only those that are an HLA-haploidentical match (≥ 4/8) will be considered as a
 potential donor. NOTE: If during testing, a fully HLA-matched sibling donor is found and is
 willing to donate his/her stem cells, the potential subject will not be eligible for this
 protocol.

 Donor consent will be obtained as per standard protocol of the bone marrow transplant unit.