Conditions: Hemophagocytic Lymphohistiocytosis X-Linked Lymphoproliferative Disorders Chediak-Higashi Syndrome Griscelli Syndrome Immunologic Deficiency Syndromes Langerhans-Cell Histiocytosis
Keywords: Stem cell transplant immunodeficiency donor lymphocyte infusion
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 19
Healthy volunteers: no

Brief 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).

Detailed description:
Prior to transplantation, subjects will receive Melphalan, Fludarabine and Anti-Thymocyte Globulin (ATG) or Campath. These three drugs are being given to subjects to help the new stem cells take and grow. On the day of transplantation, subjects will receive stem cells transfused via intravenous (IV) catheter.

After stem cell transplantation, subjects will be given Cyclosporin A (CsA) and mycophenolate mofetil (MMF) to reduce the risk of graft-versus-host disease, the complication that occurs when the donor's stem cells react against the patient.

Arms:
arm 1: Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG) arm 2: Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG) arm 3: Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)

Interventions: intervention 1: Stem Cell Transplant intervention 2: Fludarabine intervention 3: Melphalan intervention 4: Anti-thymocyte globulin (ATG) intervention 5: Campath 1H intervention 6: Cyclosporin A intervention 7: Mycophenolate mofetil intervention 8: Intravenous immunoglobulin (IVIG)
Intervention descriptions: intervention 1: IV on Day 0 intervention 2: 30mg/m\^2 IV Day -7 through Day -3 intervention 3: 140 mg/m\^2 IV Day -1 intervention 4: 30 mg/kg IV Day -5 through Day -1 intervention 5: 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 intervention 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 intervention 7: 15 mg/kg IV or orally bid and discontinued on Day +45 unless GVHD is present intervention 8: 500 mg/kg IV weekly beginning on Day +7 until Day +100

Protocol document: