|Elizabeth Stenger, MD, MSc|
|Ben Watkins, MD|
9 United States sites
< 20 Years
Patients with sickle cell disease (stratum 1) must be between the ages of 3-20.99 years and patients with other diseases (stratum 2) between the ages of 0-20.99 years at the time of admission for transplant.
Must have one of the following diseases:
Chronic granulomatous disease
Severe congenital neutropenia (with resistance to granulocyte colony-stimulating factor (GCSF) or chronic requirement of GCSF doses ≥10 mcg/kg)
Leukocyte adhesion deficiency
Diamond-Blackfan Anemia (DBA; transfusion dependent, including steroid failure or inability to wean steroids)
Chediak Higashi syndrome
Acquired (immune; non-inherited, non-congenital) SAA
Any genotypic form of SCD with severe disease, defined as one or more of the following criteria:
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 the following:
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.
Cerebral arteriopathy, as evidenced by abnormal TCD testing (confirmed elevated velocities in any single vessel of time-averaged mean of the maximum velocity (TAMMV) > 200 cm/sec for non-imaging TCD) or by significant vasculopathy on magnetic resonance angiograph (MRA; greater than 50% stenosis of > 2 arterial segments or complete occlusion of any single arterial segment).
Frequent (3 or more per year for preceding 2 years) painful vaso-occlusive episodes (defined as episode lasting 4 hours or more and requiring hospitalization or outpatient treatment with parenteral opioids). If patient is on hydroxyurea and its use has been associated with a decrease in the frequency of episodes, the frequency should be gauged from the 2 years prior to the start of this drug.
Recurrent (3 or more in lifetime) acute chest syndrome events which have necessitated erythrocyte transfusion therapy.
Any combination of 3 or more acute chest syndrome episodes and vaso-occlusive pain episodes (defined as above) yearly for 3 years. If patient is on hydroxurea and its use has been associated with a decrease in the frequency of episodes, the frequency should be gauged from the 3 years prior to the start of this drug.
Other inherited or congenital marrow failure syndromes complicated by SAA
Other inherited or congenital red blood cell disorders requiring monthly chronic transfusion therapy.
Congenital platelet disorders requiring frequent platelet transfusions (patient must have received at least 10 transfusions in the last 3 years).
Other inherited or congenital granulocyte disorders resulting in at least three inpatient hospitalizations in the past three years for infection.
Must have an unrelated adult donor (marrow or PBSC) who is a 7 or 8/8 match
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.
Must have been evaluated and adequately counseled regarding treatment options by a pediatric hematologist.
Negative serum pregnancy test for females of childbearing potential only. Pregnancy must be excluded before the start of treatment with study drugs and prevented thereafter by reliable contraceptive methods.
HLA matched related donor
Pulmonary dysfunction defined as diffusing capacity of the lungs for carbon monoxide (DLCO; corrected for hemoglobin), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) < 40% of predicted. In a child unable to perform pulmonary function testing, a chronic need for supplemental oxygen will serve as the exclusionary criterion. Renal dysfunction defined as estimated glomerular filtration rate (GFR) of <60 ml/min/1.73m2. Severe cardiac dysfunction defined as shortening fraction < 25%. Bridging (portal to portal) fibrosis or cirrhosis of the liver Clinical stroke within 6 months of anticipated transplant Karnofsky or Lansky functional performance score < 50% HIV infection Uncontrolled viral, bacterial, fungal, or protozoal infection at the time of study enrollment. Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate HSCT. Patient or patient's guardian(s) unable to understand the nature and risks inherent in the HSCT process. History of non-compliance severe enough in the estimation of the treating team to preclude the patient from undergoing unrelated donor transplantation. Patient is pregnant or lactating. Patient with a 7/8 URD donor and HLA antibody testing (see below) demonstrating an antibody directed against a donor disparate HLA molecule.