Toward a Less Toxic Yet Highly Effective Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Children and Adolescents with Severe Sickle Cell Disease: a Pilot Study

Study ID
STU 112010-010

Cancer Related

Healthy Volunteers

Study Sites

Niechelle Loyd

Principal Investigator
Victor Aquino


Fludarabine, a non-vasculopathic, non-gonadotoxic agent, amplifies the engraftment promoting effects of Cy; in an effort to lessen the incidence of transplant related neurotoxicity and gonadotoxicity, we will conduct a pilot study in which fludarabine is added to BuCyaTG for conditioning, and the dose of Bu and Cy are reduced using a stepwise de-escalation schema. This study will serve as a forerunner to larger trial designed to test the safety and efficacy of a reduced toxicity BuFluCyaTG regimen. a total of 24 patients will be enrolled at all centers. We anticipate a total of 3 subjects to be enrolled locally. Patients will participate in the study for 5 years.

Participant Eligibility

Patients up to and including the age of 18 years at time of admission for transplant, Hemoglobin SS, or hemoglobin S[BETA]0 thalassemia, HLA-identical sibling donor (any age) available without HgbSS, SC or S[BETA]0 thalassemia. As an alternative, HLA identical sibling umbilical cord blood can be used as long as the unit has a pre-cryopreservation TNC dose of greater than 5.0 x 107 TNC/kg recipient weight. Clinically severe SCD, defined by one of the following: Previous clinical stroke, as evidenced by a neurological deficit lasting longer than 24 hours, which is accompanied by radiographic evidence of ischemic brain injury and cerebral vasculopathy. Asymptomatic cerebrovascular disease, as evidenced by one of the following: (i) Progressive silent cerebral infarction, as evidenced by serial MRI scans that demonstrate the development of a succession of lesions (at least two temporally discreet lesions, each measuring at least 3 mm in greatest dimension on the most recent scan) or the enlargement of a single lesion, initially measuring at least 3 mm). Lesions must be visible on T2-weighted MRI sequences. (ii) Cerebral arteriopathy, as evidenced by abnormal TCD testing (confirmed elevated velocities in any single vessel of TAMMV > 200 cm/sec for non-imaging TCD or TAMX > 185 cm/sec for imaging TCD) or by significant vasculopathy on MRA (greater than 50% stenosis of > 2 arterial segments or complete occlusion of any single arterial segment). Frequent (>= 3 per year for 2 years) painful vaso-occlusive episodes (defined as episode lasting >= 4 hours and requiring hospitalization or outpatient treatment with parenteral narcotics) . Recurrent (>= 3 in lifetime) acute chest syndrome events which have necessitated exchange transfusion or chronic transfusion therapy. Any combination of >= 3 acute chest syndrome episodes and vaso-occlusive pain episodes (defined as above) yearly for 3 years. Stage I or II sickle lung disease. Must have been evaluated and adequately counseled regarding treatment options for severe sickle cell disease by a pediatric hematologist. All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.