|Elizabeth Stenger, MD, MSc|
|Ben Watkins, MD|
7 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:
– Glanzmann thrombasthenia
– 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
– Shwachman-Diamond syndrome
– Diamond-Blackfan Anemia (DBA; transfusion dependent, including steroid failure or
inability to wean steroids)
– Thalassemia major
– Dyskeratosis congenita
– 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
– 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
– 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
– Must have been evaluated and adequately counseled regarding treatment options by a
– 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.