Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies - Full Text View

Study Description

Brief Summary:

OBJECTIVES: I. Provide curative immunoreconstituting allogeneic bone marrow transplantation for patients with primary immunodeficiencies.

II. Determine relevant outcomes of this treatment in these patients including quality of survival, extent of morbidity and mortality from complications of the treatment (e.g., graft versus host disease, regimen related toxicities, B- cell lymphoproliferative disease), and completeness of functional immunoreconstitution.

Condition or disease	Intervention/treatment	Phase
Immunologic Deficiency Syndromes Chediak-Higashi Syndrome Common Variable Immunodeficiency Graft Versus Host Disease X-Linked Lymphoproliferative Syndrome Familial Erythrophagocytic Lymphohistiocytosis Hemophagocytic Lymphohistiocytosis X-linked Agammaglobulinemia Wiskott-Aldrich Syndrome Chronic Granulomatous Disease X-linked Hyper IgM Syndrome Severe Combined Immunodeficiency Leukocyte Adhesion Deficiency Syndrome Virus-Associated Hemophagocytic Syndrome	Drug: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: etoposide Drug: methotrexate Drug: methylprednisolone Drug: prednisone Procedure: Allogeneic Bone Marrow Transplantation	Not Applicable

Detailed Description:

PROTOCOL OUTLINE: Patients with severe combined immunodeficiency (SCID) using a matched sibling donor receive allogeneic bone marrow or umbilical cord blood transplantation on day 0. Patients receive graft versus host disease (GVHD) prophylaxis with methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV on days -3 to 50.

Patients with SCID using donors other than histocompatible siblings, Wiskott Aldrich syndrome using a histocompatible sibling donor, Wiskott Aldrich syndrome and under 5 years of age using donors other than histocompatible siblings, X-linked CD40 ligand deficiency using a histocompatible sibling donor, X-linked CD40 ligand deficiency and under 5 years of age using donors other than histocompatible siblings, other primary immunodeficiencies without manifestations of hemophagocytosis using a histocompatible sibling donor, or other primary immunodeficiencies without manifestations of hemophagocytosis and under 5 years of age using donors other than histocompatible siblings receive busulfan IV over 2 hours every 6 hours on days -9 to -6, cyclophosphamide IV on days -5 to -2, and antithymocyte globulin (ATG) twice daily on days -4 to -1. Allogeneic bone marrow or umbilical cord blood transplantation takes place on day 0. Patients receive graft versus host disease (GVHD) prophylaxis with methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV on days -3 to 50.

Patients with hemophagocytic lymphohistiocytosis, Chediak Higashi syndrome, X-linked lymphoproliferative syndrome, severe progressive Langerhans cell histiocytosis, or other primary immunodeficiencies with complications of hemophagocytosis receive busulfan IV over 2 hours every 6 hours on days -9 to -6, cyclophosphamide IV over 2 hours on days -5 to -2, etoposide IV over 22 hours on days -5 to -3, and ATG IV twice daily on days -2, -1, 1, and 2. Allogeneic bone marrow or umbilical cord blood transplantation takes place on day 0. Patients receive graft versus host disease (GVHD) prophylaxis with methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV on days -3 to 50.

Patients with Wiskott Aldrich syndrome or other primary immunodeficiencies without manifestations of hemophagocytosis, who are over 5 years of age and using donors other than histocompatible siblings, receive busulfan IV over 2 hours every 6 hours on days -6 and -5, cyclophosphamide IV over 2 hours on days -4 and -3, total body irradiation on day -2, and ATG IV over 2 hours twice daily on days -2, -1, 2, and 3. Allogeneic bone marrow or umbilical cord blood transplantation takes place on days 0 and 1. Patients receive GVHD prophylaxis with methylprednisolone IV every 12 hours on days 2-21, oral prednisone every 12 hours on days 22-100 and then tapered off over days 101 to 128, and cyclosporine IV over 2 hours every 8-12 hours on days -3 to 100.

All patients are followed as determined by their primary physician.

Study Design


Study Type :	Interventional (Clinical Trial)
Primary Purpose:	Treatment
Study Start Date :	March 2000
Actual Primary Completion Date :	December 2002
Actual Study Completion Date :	December 2002

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Chediak-Higashi syndrome JAK3-deficient severe combined immunodeficiency MDA5 deficiency Omenn syndrome Wiskott-Aldrich syndrome X-linked agammaglobulinemia X-linked hyper IgM syndrome X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia X-linked severe combined immunodeficiency ZAP70-related severe combined immunodeficiency Adenosine deaminase deficiency Chronic granulomatous disease Common variable immune deficiency Familial hemophagocytic lymphohistiocytosis Leukocyte adhesion deficiency type 1 Purine nucleoside phosphorylase deficiency

MedlinePlus related topics: Bone Marrow Transplantation

Genetic and Rare Diseases Information Center resources: Homologous Wasting Disease Severe Combined Immunodeficiency Common Variable Immunodeficiency Wiskott Aldrich Syndrome Chronic Granulomatous Disease Hemophagocytic Lymphohistiocytosis Langerhans Cell Histiocytosis X-linked Agammaglobulinemia X-linked Lymphoproliferative Syndrome Immunodeficiency With Hyper IgM Type 1 Chediak-Higashi Syndrome Virus Associated Hemophagocytic Syndrome

U.S. FDA Resources

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	up to 35 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Severe combined immunodeficiency All ages with histocompatible sibling donors or with other donors OR Wiskott Aldrich syndrome All ages with histocompatible sibling donors or with other donors OR X-linked CD40 ligand deficiency All ages with histocompatible sibling donors OR Under 5 years of age with donors other than histocompatible siblings OR Other primary immunodeficiencies without manifestations of hemophagocytosis All ages with histocompatible sibling donors or with other donors OR Hemophagocytic lymphohistiocytosis (HLH) Familial erythrophagocytic lymphohistiocytosis (FEL), familial HLH (FHLH), recurrent virus-associated hemophagocytic syndrome (VAHS) All ages with related or unrelated donors OR Chediak Higashi syndrome All ages with related or unrelated donors OR X-linked lymphoproliferative syndrome All ages with related or unrelated donors OR Other primary immunodeficiencies with complication of hemophagocytosis All ages with related or unrelated donors OR Severe progressive Langerhans cell histiocytosis All ages with related or unrelated donors

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006054

Locations


United States, Minnesota
Fairview University Medical Center
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Fairview University Medical Center

Investigators


Study Chair:	K. Scott Baker	Fairview University Medical Center

More Information


ClinicalTrials.gov Identifier:	NCT00006054 History of Changes
Other Study ID Numbers:	199/15104 UMN-MT-1995-26 UMN-MT-9526
First Posted:	July 6, 2000 Key Record Dates
Last Update Posted:	October 15, 2009
Last Verified:	October 2003

Keywords provided by Office of Rare Diseases (ORD):


familial erythrophagocytic lymphohistiocytosis hemophagocytic lymphohistiocytosis Chediak-Higashi syndrome Langerhans cell histiocytosis Wiskott-Aldrich syndrome X-linked agammaglobulinemia X-linked hyper IgM syndrome X-linked lymphoproliferative syndrome chronic granulomatous disease common variable immunodeficiency complement deficiency	disease-related problem/condition genetic diseases and dysmorphic syndromes graft versus host disease hematologic disorders histiocytosis immunologic disorders and infectious disorders leukocyte adhesion deficiency syndrome primary immunodeficiency disease rare disease severe combined immunodeficiency virus-associated hemophagocytic syndrome

Additional relevant MeSH terms:


Syndrome Immunologic Deficiency Syndromes Graft vs Host Disease Tissue Adhesions Granuloma Granulomatous Disease, Chronic Severe Combined Immunodeficiency Lymphohistiocytosis, Hemophagocytic Wiskott-Aldrich Syndrome Common Variable Immunodeficiency Agammaglobulinemia Chediak-Higashi Syndrome Hyper-IgM Immunodeficiency Syndrome Hyper-IgM Immunodeficiency Syndrome, Type 1 Genetic Diseases, X-Linked	Leukocyte-Adhesion Deficiency Syndrome Lymphoproliferative Disorders Disease Pathologic Processes Immune System Diseases Cicatrix Fibrosis Lymphatic Diseases Phagocyte Bactericidal Dysfunction Leukocyte Disorders Hematologic Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases DNA Repair-Deficiency Disorders Metabolic Diseases