Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis

OBJECTIVES: Primary * To determine the overall and disease-free survival of poor-risk pediatric patients with Langerhans cell histiocytosis at 1 and 3 years after reduced-intensity hematopoietic cell transplantation (RI-HCT). Secondary * To determine day 100 transplantation-related mortality. * To determine the incidence of hematopoietic recovery and chimerism at day 100 and at 1 year post RI-HCT. * To determine the incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD). * To determine the incidence of chronic GVHD. OUTLINE: This is a multicenter study. * Non-myeloablative conditioning: Patients receive alemtuzumab intravenously (IV) over 2 hours on days -8 to -4, fludarabine phosphate IV over 30-60 minutes on days -7 to -3, and melphalan IV over 15-30 minutes on day -2. Some patients may receive anti-thymocyte globulin IV on days -6 to -2 instead of alemtuzumab. * Graft-versus-host disease prophylaxis and immunosuppression: Patients receive cyclosporine A (CSA) IV or orally 2-3 times daily beginning on day -3 and continuing until day 50 post transplantation, followed by a taper over 8 weeks in the absence of GVHD or donor lymphocyte infusion given for decreasing donor chimerism. Patients with mismatched donors (any source) and those receiving peripheral blood stem cells also receive mycophenolate mofetil (MMF) IV or orally 2-3 times daily beginning on day -3 and continuing to day 30 or 7 days after engraftment, whichever day is later, in the absence of GVHD. In patients with acute GVHD requiring systemic therapy, Mycophenolate mofetil (MMF) may be stopped 7 days after initiation of systemic therapy. * Allogeneic hematopoietic stem cell infusion: Patients undergo infusion of bone marrow (preferred) or peripheral blood stem cells on day 0. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 8 and continuing until blood counts recover for 2 consecutive days. * Donor lymphocyte infusion (DLI): Patients with mixed chimerism (i.e., \< 95% donor) and those with \< 50% donor T-cell engraftment at any engraftment assessment time point are eligible for DLI, in the absence of GVHD. If mixed chimerism persists, escalating doses of CD3-positive lymphocytes are administered every 3-4 weeks, in the absence of GVHD. After completion of study therapy, patients are followed from engraftment through day 100, and then at 6 months, 1 year, and annually thereafter for 2-5 years.