This is a clinical trial of bone marrow transplantation for patients with the diagnosis of a
genetic disease of blood cells that do not have an HLA-matched sibling donor. Genetic
diseases of blood cell include: Red blood cell defects e.g. hemoglobinopathies (sickle cell
disease and thalassemia), Blackfan-Diamond anemia and congenital or chronic hemolytic
anemias; White blood cells defects/immune deficiencies e.g. chronic granulomatous disease,
Wiskott-Aldrich syndrome,Osteopetrosis, Kostmann's syndrome (congenital neutropenia),
Hereditary Lymphohistiocytosis (HLH); Platelets defects e.g.Congenital amegakaryocytic
thrombocytopenia; Metabolic/storage disorders e.g. leukodystrophies,mucopolysaccharidoses as
Hurler disease;Stem cell defects e.g.reticular agenesis, among many other rare similar
The study treatment plan uses a new transplant treatment regimen that aims to try to
decrease the acute toxicities and complications associated with the standard treatment plans
and to improve outcome
The blood stem cells will be derived from either unrelated donor or unrelated umbilical cord
This is a pilot clinical trial of hematopoietic stem cell transplantation for patients with
the diagnosis of a genetic disease of blood cells that do not have an HLA-matched sibling
donor. The stem cells will be derived from a 1) matched unrelated donor (MUD) or 2)
unrelated umbilical cord blood (UCB). Patients will receive a novel conditioning regimen
with Busulfan, Cytoxan and Fludarabine (Bu/Cy/Flu) and either Alemtuzumab (Campath 1H) for
recipients of a MUD or rabbit Antithymocyte Globulin (rATG) for recipients of unrelated UCB
prior to hematopoietic stem cell transplant (HSCT).
It is hypothesized that reduced dosages of Cytoxan will decrease the acute toxicities
associated with the standard chemotherapies of Busulfan and Cytoxan (i.e. sinusoidal
obstructive syndrome (SOS), hemorrhagic cystitis and mucositis). And the addition of
fludarabine to a conditioning regimen with myeloablative doses of Busulfan and reduced
dosages of Cytoxan prior to HSCT will overcome the engraftment barrier posed by an intact
immune system, which is seen in patients with a genetic disease.
- Lethal or sublethal genetic disease of blood cells, who lack a fully histocompatible
sibling or other family donor
- Genetic diseases that would be candidates for this protocol includes those that have
been shown to benefit from allogeneic HSCT: Red blood cell defects, Leukocyte
defects/ Primary immune deficiencies, Platelets defects, Metabolic/storage disorders
and Stem cell defects.
- Renal: creatinine clearance or glomerular filtration rate (GFR) ≥50 ml/min/1.73m2 and
not requiring dialysis.
- Pulmonary: FEV1, FVC and DLCO (corrected for hemoglobin) ≥ 50% predicted. if unable
to perform pulmonary function tests, then O2 saturation ≥ 92% in room air.
- Cardiac: Left ventricular ejection fraction at rest must be ≥ 40%, or shortening
fraction ≥ 26%
- Hepatic: Bilirubin ≤3x upper limit of normal (ULN) and ALT and AST ≤ 5x for age (with
the exception of isolated hyperbilirubinemia due to Gilbert's syndrome).
- Patients will be 0-21 years of age.
- Disease specific inclusion criteria (as applicable per protocol).
- Recipients should not have any of the general exclusion criteria, and disease
specific exclusion criteria when applicable.
- Patient with histocompatible sibling
- End-organ failure that precludes the ability to tolerate the transplant procedure,
including the conditioning regimen.
- Creatinine clearance or GFR < 50 ml/min/1.73m2 or renal failure requiring dialysis.
- Congenital heart disease resulting in congestive heart failure.
- Severe residual CNS disease/impairment [(other than hemiplegia alone) e.g. coma or
- Ventilatory failure
- Major congenital anomalies that adversely affect survival, e.g. CNS malformations
- Lansky score < 40% or Karnofsky score < 60%
- HIV seropositivity
- Diagnosis of Fanconi's anemia, Severe Combined Immunodeficiency (SCID)
- Positive pregnancy test (For female patients in child bearing period)
- Uncontrolled bacterial, viral, or fungal infections (currently taking medication yet
clinical symptoms progress)
- Disease specific exclusion criteria (as applicable per protocol).
Hisham Abdel-Azim, MD
Childrens Hospital Los Angeles, University of Southern California