Stem Cell Transplant for Immunologic or Histiocytic Disorders
Condition: Hemophagocytic Lymphohistiocytosis; X-Linked Lymphoproliferative Disorders; Chediak-Higashi Syndrome; Griscelli Syndrome; Immunologic Deficiency Syndromes; Langerhans-Cell Histiocytosis
MeSH terms: Histiocytosis, Langerhans-Cell; Chediak-Higashi Syndrome; Lymphoproliferative Disorders; Histiocytosis; Lymphohistiocytosis, Hemophagocytic; Immunologic Deficiency Syndromes; Syndrome
Intervention: Stem Cell Transplant; Fludarabine; Melphalan; Anti-thymocyte globulin (ATG); Campath 1H; Cyclosporin A; Mycophenolate mofetil; Intravenous immunoglobulin (IVIG)
Intervention description: IV on Day 0; 30mg/m^2 IV Day -7 through Day -3; 140 mg/m^2 IV Day -1; 30 mg/kg IV Day -5 through Day -1; 0.2 mg/kg IV X 5 days (used as an alternative to Anti-thymocyte globulin (ATG) if unable to tolerate ATG) Day -10 through Day -6; 2.5 mg/kg IV every 12 hours (adults) or every 8 hours (children <40 kg) maintaining a level of >200mg/L Day -3 until Day +180 when, if no GVHD, the dose will be tapered 10% per week beginning on day 181; 15 mg/kg IV or orally bid and discontinued on Day +45 unless GVHD is present; 500 mg/kg IV weekly beginning on Day +7 until Day +100
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Fludarabine; Melphalan; Alemtuzumab; Cyclosporins; Antilymphocyte Serum; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Maximum age: 35 Years
Healthy volunteers: No
Keywords: Stem cell transplant; immunodeficiency; donor lymphocyte infusion

Summary:

      This study tests the clinical outcomes of a preparative regimen of fludarabine (FLU),
      anti-thymocyte globulin (ATG)/or Campath, and melphalan; followed by hematopoietic stem cell
      transplant, and a post transplant regimen of Cyclosporin A (CsA) in patients with immunologic
      or histiocytic disorders. The researchers hypothesize that this regimen will have a positive
      effect on post transplant engraftment and the incidence of graft-versus-host-disease (GVHD).

      Patients will be randomized biologically into one of 3 arms based upon donor availability:
      (a) human leukocyte antigen (HLA) genotypic matched sibling donor, (b) HLA phenotypic matched
      unrelated peripheral blood stem cell (PBSC) donor, (c) two HLA 0-2 antigen mismatched
      unrelated cord blood donors (double cord).
    

Eligibility criteria:

        Inclusion Criteria:

        Patients with immunodeficiencies or histiocytic disorders 0-35 years of age with an
        acceptable stem cell donor and disease characteristic defined by the following:

          -  Patients with histocytic disorders (hemophagocytic lymphohistiocytosis of any etiology
             and refractory Langerhans cell histiocytosis) who do not meet eligibility criteria for
             a myeloablative transplant procedure

          -  Patients with immunodeficiency disorders in whom residual immune function may not
             require a fully myeloablative preparative regimen or patient is ineligible for
             standard myeloablative preparative regimen (any form of severe combined
             immunodeficiency [SCID], or other immunodeficiency with T cell defect)

          -  Patients with immunodeficiency disorders that have had poor outcome with myeloablative
             stem cell transplants (including, but not limited to, common variable immunodeficiency
             [CVID], Wiskott Aldrich Syndrome [WAS] if > 5 years of age, ataxia telangiectasia)

          -  Patients with immunodeficiencies or histocytic disorders that require a second stem
             cell transplant (SCT) for any reason

        Exclusion Criteria:

          -  Karnofsky or Lansky performance score <70

          -  Glomerular filtration rate (GFR)<30% predicted

          -  Cardiac function <50% normal by echocardiogram

          -  Serum creatinine > 2x normal for age/weight

          -  Pregnant or lactating females

          -  Active serious infection that has not had an adequate course of therapy pre-SCT. Any
             patient with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC)
             or human immunodeficiency virus (HIV) seropositivity