Congenital Bone Marrow Failure Syndromes, Hereditary Anemias, Inflammatory Conditions, Inherited Metabolic Disorders (IMD), Primary Immunodeficiency (PID)
Conditions
Keywords
Severe Combined Immune Deficiency (SCID) with NK cell activity, Omenn Syndrome, Bare Lymphocyte Syndrome (BLS), Combined Immune Deficiency (CID) syndromes, 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, Congenital Amegakaryocytic Thrombocytopenia (CAMT), Osteopetrosis, Hurler syndrome (MPS I), Hurler syndrome (MPS II), Krabbe Disease, also known as Globoid Cell Leukodystrophy, Metachromatic leukodystrophy (MLD), X-linked adrenoleukodystrophy (ALD), Alpha Mannosidosis, Gaucher Disease, Thalassemia major, Sickle cell disease (SCD), Diamond Blackfan Anemia (DBA), Crohn's Disease, Inflammatory Bowel Disease, IPEX or IPEX-like Syndromes, Rheumatoid Arthritis
Brief summary
This is a data collection study that will examine the general diagnostic and treatment data associated with the reduced-intensity chemotherapy-based regimen paired with simple alemtuzumab dosing strata designed to prevented graft failure and to aid in immune reconstitution following hematopoietic stem cell transplantation.
Detailed 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.
Interventions
DRUGdata collection
Study subjects will receive alemtuzumab, melphalan, thiotepa, fludarabine and hydroxyurea-based, reduced-intensity conditioning regimen in accordance with clinical practice at UPMC Children's Hospital of Pittsburgh at the discretion of the treating physician. Medical data will be abstracted from subject's medical charts once the patient signs the informed consent.
Sponsors
Paul Szabolcs
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
2 Months to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Patient, parent, or legal guardian must have given written informed consent. 2. Patient must be 2 months to 60 years (inclusive) of age at time of consent for all diagnoses. 3. 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 4. 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
.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| incidence of acute graft versus host disease (GVHD) | up to 5 years | grades 3-4, chronic extensive GVHD |
| overall survival after HSCT | up to 5 years | review of the existing medical records to check on the participant's survival status |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Describe degree of engraftment, based upon chimerism data | up to 5 years | review of chimerism test results in the existing medical records to check on degree of donor engraftment measured by the percentage of donor-derived blood cells in the HSCT recipient |
| Describe probability to discontinue systemic immunosuppression medications | by 6, 9, and 12 months post-HSCT | review of the existing medical records to check on the participant's current medications |
| Describe the tempo of immune reconstitution | over the first year post transplant | review of the various test results in existing medical records to check on the participant's immune system recovery rate |
| Describe the use of donor leukocyte infusion (DLI) | up to 5 years | review of the existing medical records to check on the participant's need for DLI |
Countries
United States
Contacts
Primary ContactPaul Szabolcs, MD
Backup ContactShawna McIntyre, RN
Outcome results
None listed