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Key inclusion & exclusion criteria
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Inclusion Criteria:
- Must be between the ages of 0-21 years at the time of admission for transplant.
- Must have one of the following diseases:
1. Glanzmann thrombasthenia
2. Wiskott-Aldrich syndrome or other combined immune deficiency
3. Chronic-granulomatous disease
4. Severe congenital neutropenia (with resistance to granulocyte-colony stimulating
factor (GCSF) or chronic requirement of GCSF doses =10 mcg/kg)
5. Leukocyte adhesion deficiency
6. Shwachman-Diamond syndrome
7. Diamond-Blackfan anemia ((transfusion dependent, including steroid failure or
inability to wean steroids)
8. Thalassemia major
9. Fanconi anemia
10. Hemophagocytic lymphohistiocytosis (inherited or acquired refractory to therapy
or with recurrent episodes of hyperinflammation)
11. Dyskeratosis-congenita
12. Hurler Syndrome
13. Chediak-Higashi syndrome
14. Acquired (immune; non-inherited, non-congenital) severe aplastic anemia
15. Sickle cell disease (SCD) (Hgb SS or S-Beta 0 thalassemia) will be eligible
between ages 3 and 9.99 and with severe disease.
16. Other inherited or congenital marrow failure syndromes complicated by severe
aplastic anemia
17. Other inherited or congenital red blood cell disorders requiring monthly chronic
transfusion therapy.
18. Congenital platelet disorders requiring frequent platelet transfusions (patient
must have received at least 10 transfusions in the last 3 years).
19. 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 at least a 7/8 match (A, B,
C, DRB1; the mismatch can be at an allele or antigen level) or an unrelated cord blood
unit that is matched at least seven of eight loci (A, B and C antigen level-DRB1
allele level) and provides a minimum pre-cryopreservation total nucleated cell (TNC)
dose of 7.5 x 107 TNC/kg recipient weight. Mismatches at the DRB1 locus may be at an
antigen or allele level.
Exclusion Criteria:
- Human leukocyte antigen (HLA) matched related donor.
- Severe combined immune deficiency.
- Bridging (portal to portal) fibrosis or cirrhosis of the liver.
- Pulmonary: diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for
hemoglobin), forced expiratory volume (FEV1) or forced vital capacity (FVC) < 40% of
predicted. In child unable to perform pulmonary function testing, a chronic need for
supplemental oxygen will serve as the exclusionary criterion.
- Severe renal dysfunction defined as estimated glomerular filtration rate (GFR) of <60
ml/min/1.73m2.
- Severe cardiac dysfunction defined as shortening fraction < 25%.
- Neurologic impairment other than hemiplegia, defined as full-scale intelligence
quotient (IQ) less than or equal to 70, quadriplegia or paraplegia, inability to
ambulate, or any impairment resulting in decline of Lansky performance score to < 70%.
- 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 bone marrow transplantation.
- Patient or patient's guardian(s) unable to understand the nature and risks inherent in
the blood and marrow transplant 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
- Patients HLA antibody testing demonstrates an antibody directed against a disparate
HLA molecule.
Age minimum:
N/A
Age maximum:
21 Years
Gender:
All
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Secondary Outcome(s)
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Immune Suppression-Free and Disease-Free Survival Rate
[Time Frame: 1 year post-transplant]
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Immune Suppression-Free Survival Rate
[Time Frame: 1 year post-transplant]
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Number of Participants Experiencing Chronic GVHD
[Time Frame: 2 years post-transplant]
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Number of Participants with Non-engraftment
[Time Frame: 1 year post-transplant]
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Number of Participants Experiencing Acute Graft Versus Host Disease (GVHD)
[Time Frame: Up to 1 year post-transplant]
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Days until Platelet Recovery
[Time Frame: 1 year post-transplant]
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Number of Participants Experiencing Other Infections
[Time Frame: 1 year post-transplant]
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Days until Neutrophil Recovery
[Time Frame: 1 year post-transplant]
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Number of Participants Experiencing Immune Reconstitution
[Time Frame: 1 year post-transplant]
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Number of Participants with Secondary Graft Failure
[Time Frame: 1 year post-transplant]
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Disease-free Survival Rate
[Time Frame: 1 year post-transplant]
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Number of Participants Experiencing Cytomegalovirus (CMV) Viremia
[Time Frame: Up to Day 180]
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Number of Participants Experiencing Post-transplant Lymphoproliferative Disorder (PTLD)
[Time Frame: 1 year post-transplant]
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Number of Participants Experiencing CMV Invasive Disease
[Time Frame: 1 year post-transplant]
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Number of Participants with Graft Loss
[Time Frame: 1 year post-transplant]
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Proportion of Participants Experiencing Regimen-related Toxicity (RRT)
[Time Frame: Day 42 post-transplant]
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Overall Survival Rate
[Time Frame: 1 year post-transplant]
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