Data Collection Study of Patients With Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT With RIC

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective Outcomes Study of Pediatric and Adult Patients With Non-Malignant Disorders Undergoing Umbilical Cord Blood, Bone Marrow, or Peripheral Blood Stem Cell Transplantation With a Reduced-Intensity Conditioning Regimen (PRO-RIC)

Conditions
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Hereditary Anemias, Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes, Inherited Metabolic Disorders (IMD), Inflammatory Conditions

Intervention / Treatment
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* Drug: data collection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: data 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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Describe degree of engraftment, based upon chimerism data | 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 | up to 5 years | 
| Describe probability to discontinue systemic immunosuppression medications | review of the existing medical records to check on the participant's current medications | by 6, 9, and 12 months post-HSCT | 
| Describe the tempo of immune reconstitution | review of the various test results in existing medical records to check on the participant's immune system recovery rate | over the first year post transplant | 
| Describe the use of donor leukocyte infusion (DLI) | review of the existing medical records to check on the participant's need for DLI | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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