The design of the study incorporates the following features:
This is a phase II study to determine the safety and therapeutic potential of a new
transplant approach (disease-free survival, graft versus myeloma effect) and to evaluate
its toxicity profile (immediate toxicity, graft-versus-host disease, graft rejection,
mortality) in a patient population with severe congenital anemias.
The patient cohort to be studied: Those patients with severe sickle cell disease and
thalassemia who have risk factors for high mortality and morbidity related to their
Transplant Conditioning Regimen - Immunosuppression without myeloablation: Patients will
receive conditioning sufficient to allow donor lympho-hematopoietic engraftment without
complete marrow ablation. If the graft is rejected, the patient will reconstitute
autologous marrow function. We will use a combination of low dose irradiation,
Alemtuzumab (Campath), and sirolimus.
Peripheral blood hematopoietic progenitor cell (PBPC) transplant: An unmanipulated
peripheral blood stem cell collection from a filgrastim (G-CSF) stimulated HLA-matched
donor should improve the chance of engraftment because of the high stem cell dose (5 x
106/kg CD34+ cells) and the presence of donor lymphocytes. To reduce the risk of GVHD,
patients will receive sirolimus before and after the transplant. The sirolimus will be
tapered as necessary to minimize any graft versus host disease while still maintaining
A human lymphocyte antigen (HLA)-matched sibling donor will receive filgrastim (G-CSF) 10
to16 g/kg/d subcutaneously or intravenously for up to 6 days with apheresis collections of
PBPC on day 5 (and day 6 if required). The product will be collected by leukophoresis with a
goal of 10 x 106 CD34+ cells/kg, with a minimum of 5 x 106 CD34+ cells/kg.
The patient will receive a preparative regimen of Alemtuzumab to be infused on days -7 to -3,
followed by 300 cGy TBI given as a single dose on day -2. Sirolimus at a dose of 5mg/day to
maintain trough levels between 10-15ng/ml will be started on day -1. The PBPC graft targeted
to deliver 10 x 106 CD34+ cells/kg (at minimum, 5 x 106 CD34+ cells/kg) will be infused on
day 0 On days +14, +30, +60 and +100 the chimeric status of patients will be assessed by
microsatellite analysis of the peripheral blood. More frequent monitoring may be required.
Sickle cell patients with pulmonary hypertension will meet with a Pulmonary Medicine Consult
to determine appropriate management prior to SCT.
Patients with fever or suspected minor infection should await resolution of symptoms before
starting the conditioning regimen.
Iron chelation must be discontinued > 48 hours before initiating the conditioning regimen.
Hydroxyurea must be discontinued one day prior to initiating the conditioning regimen.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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