Matched Related Donor Non-myeloablative Hematopoietic Cell Transplantation With Alemtuzumab, 400 cGy TBI, and Abatacept for Sickle Cell Disease and Beta-Thalassemia
National Heart, Lung, and Blood Institute (NHLBI)
Summary
This is a non-ablative (partial) stem cell transplant for patients with severe sickle cell disease or beta-thalassemia requiring red cell transfusions. The intensity of the transplant is slightly increased from our previous transplant regimens. The goal is to aim for higher percentage of donor cells to stably remain in the recipients long term.
Description
Study Description: Our prior non-myeloablative conditioning regimen (03H0170) included 1mg/kg of alemtuzumab divided over 5 days, 300 cGy total body irradiation (TBI), and sirolimus for immune suppression. Sickle disease-free survival (DFS) and overall survival (OS) were 85% and 94% respectively, graft failure 15%, no transplant related mortality (TRM), and acute or chronic GVHD \<5%. A large proportion of patients achieved robust (\>=95%) donor myeloid chimerism at day 30, but this proportion decreased quickly to 67.2% at 1, 64.9% at 2, and 60% at 3, and 56.9% at 4 years post-transplant. A…
Eligibility
- Age range
- 4–65 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA RECIPIENT: Participants must fulfill one disease category (1 or 2) and 3 1. Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having an end-organ damage (A, B, C, D, OR E) or complication(s) not ameliorated by sickle cell-specific therapies (F): A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI ORb B. Abnormal trans-cranial Doppler examination (\>=200 cm/s); OR C. Silent cerebral infarct defined as an infarct-like lesion based on an MRI signal a…
Interventions
- RadiationTotal Body Irradiation
Total Body Irradiation 400 cGy
- DrugAlemtuzumab
1 mg/kg
- DrugAbatacept
10 mg/kg x 6
- OtherResearch blood draw
About 5 tablespoons of blood will be collected from donors for research purposes.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland