Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies

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.

Study Overview

• Status: Terminated
• Conditions: Immunologic Deficiency Syndromes; Common Variable Immunodeficiency; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; Hemophagocytic Lymphohistiocytosis; Wiskott-Aldrich Syndrome; Graft Versus Host Disease; X-linked Agammaglobulinemia; Chediak-Higashi Syndrome; Virus-Associated Hemophagocytic Syndrome; Leukocyte Adhesion Deficiency Syndrome; X-Linked Lymphoproliferative Syndrome; Familial Erythrophagocytic Lymphohistiocytosis; X-linked Hyper IgM Syndrome
• Intervention / Treatment: Drug: cyclophosphamide; Drug: prednisone; Drug: etoposide; Drug: methotrexate; Drug: methylprednisolone; Drug: busulfan; Drug: cyclosporine; Procedure: Allogeneic Bone Marrow Transplantation; Drug: anti-thymocyte globulin

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 Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 33 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Fairview University Medical Center
• Investigators: Study Chair: K. Scott Baker, Fairview University Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2000
• Primary Completion (Actual): December 1, 2002
• Study Completion (Actual): December 1, 2002

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: July 5, 2000
• First Posted (Estimate): July 6, 2000

Study Record Updates

• Last Update Posted (Estimate): October 15, 2009
• Last Update Submitted That Met QC Criteria: October 14, 2009
• Last Verified: October 1, 2003

More Information

Terms related to this study

• Keywords: rare disease; genetic diseases and dysmorphic syndromes; hematologic disorders; hemophagocytic lymphohistiocytosis; disease-related problem/condition; immunologic disorders and infectious disorders; histiocytosis; Langerhans cell histiocytosis; graft versus host disease; common variable immunodeficiency; Wiskott-Aldrich syndrome; Chediak-Higashi syndrome; chronic granulomatous disease; X-linked agammaglobulinemia; X-linked hyper IgM syndrome; X-linked lymphoproliferative syndrome; complement deficiency; familial erythrophagocytic lymphohistiocytosis; leukocyte adhesion deficiency syndrome; primary immunodeficiency disease; severe combined immunodeficiency; virus-associated hemophagocytic syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Immune System Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Eye Diseases; Disease; Hematologic Diseases; Infant, Newborn, Diseases; Blood Coagulation Disorders, Inherited; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Protein Disorders; Eye Diseases, Hereditary; Blood Coagulation Disorders; DNA Repair-Deficiency Disorders; Leukopenia; Leukocyte Disorders; Phagocyte Bactericidal Dysfunction; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Primary Immunodeficiency Diseases; Lymphopenia; Albinism; Dysgammaglobulinemia; Syndrome; Immunologic Deficiency Syndromes; Granulomatous Disease, Chronic; Lymphoproliferative Disorders; Graft vs Host Disease; Lymphohistiocytosis, Hemophagocytic; Severe Combined Immunodeficiency; Wiskott-Aldrich Syndrome; Agammaglobulinemia; Common Variable Immunodeficiency; Chediak-Higashi Syndrome; Leukocyte-Adhesion Deficiency Syndrome; Hyper-IgM Immunodeficiency Syndrome; Hyper-IgM Immunodeficiency Syndrome, Type 1; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Antifungal Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Calcineurin Inhibitors; Methylprednisolone; Cyclophosphamide; Etoposide; Prednisone; Methotrexate; Busulfan; Antilymphocyte Serum; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 199/15104; UMN-MT-1995-26; UMN-MT-9526