start date: August 20, 2020
estimated completion: June 30, 2026
last updated: September 21, 2021
size / enrollment: 50
study description: Hematopoietic stem cell transplantation (HSCT) from a healthy donor can cure or alleviate a broad spectrum of non-malignant disorders (NMD). Although reduced-intensity conditioning (RIC) regimens promise decreased treatment-related morbidity and mortality, graft failure and infections are limiting the use of RIC in chemotherapy-naive patients. Dr. Szabolcs have completed several trials to evaluate a novel RIC regimen of alemtuzumab, hydroxyurea, fludarabine, melphalan, and thiotepa. The last trial at UPMC Children's Hospital of Pittsburgh of a highly effective and biologically rational chemotherapy-based RIC regimen paired with simple alemtuzumab dosing strata was tested and resulted in outstanding survival and remarkably low rates of graft failure. The favorable outcome described may serve as a toxicity and efficacy reference for emerging gene therapy strategies as well.
This prospective collection of clinical data will allow the investigators to further assess engraftment, GVHD, immunosuppressant use and overall survival in this patient population.
primary outcomes:
- incidence of acute graft versus host disease (GVHD)
grades 3-4, chronic extensive GVHD
- up to 5 years
overall survival after HSCT
review of the existing medical records to check on the participant's survival status
- up to 5 years
secondary outcomes:
- Describe degree of engraftment, based upon chimerism data
up to 5 years
- Describe probability to discontinue systemic immunosuppression medications
by 6, 9, and 12 months post-HSCT
- Describe the tempo of immune reconstitution
over the first year post transplant
- Describe the use of donor leukocyte infusion (DLI)
up to 5 years
inclusion criteria:
• Eligible Ages: 2 - 60
• Eligible Sexes: all
Inclusion Criteria:
Patient, parent, or legal guardian must have given written informed consent.
Patient must be 2 months to 60 years (inclusive) of age at time of consent for all diagnoses.
Patients should have a non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to the following:
A. Primary Immunodeficiency Syndromes
Severe Combined Immune Deficiency (SCID) with NK cell activity
Omenn Syndrome
Bare Lymphocyte Syndrome (BLS)
Combined Immune Deficiency (CID) syndromes
Combined Variable Immune Deficiency (CVID) syndrome
Wiskott-Aldrich Syndrome
Leukocyte adhesion deficiency
Chronic granulomatous disease (CGD)
Hyper IgM (XHIM) syndrome
IPEX syndrome
Chediak-Higashi Syndrome
Autoimmune Lymphoproliferative Syndrome (ALPS)
Hemophagocytic Lymphohistiocytosis (HLH) syndromes
Lymphocyte Signaling defects
B. Congenital Bone Marrow Failure Syndromes
Congenital Amegakaryocytic Thrombocytopenia (CAMT)
Osteopetrosis
C. Inherited Metabolic Disorders (IMD)
Mucopolysaccharidoses
Hurler syndrome (MPS I)
Hunter syndrome (MPS II)
Leukodystrophies
Krabbe Disease, also known as globoid cell leukodystrophy
Metachromatic leukodystrophy (MLD)
X-linked adrenoleukodystrophy (ALD)
Other inherited metabolic disorders
Alpha Mannosidosis
Gaucher Disease
Other inheritable metabolic diseases where HSCT may be beneficial
D. Hereditary Anemias
Thalassemia major
Sickle cell disease (SCD)
Diamond Blackfan Anemia (DBA)
E. Inflammatory Conditions
Crohn's Disease or Inflammatory Bowel Disease
IPEX or IPEX-like Syndromes
Rheumatoid Arthritis
Other inflammatory conditions where HSCT may be beneficial
Subjects receive either umbilical cord blood, bone marrow, or peripheral blood stem cell transplant with an alemtuzumab, melphalan, thiotepa, fludarabine and hydroxyurea-based, reduced-intensity conditioning regimen, according to clinical practice at UPMC Children's Hospital of Pittsburgh.
There are no exclusion criteria.
