Treatment of recurrent CNS disease post-bone marrow transplant in familial HLH.

CNS involvement in Hemophagocytic Lymphohistiocytosis (HLH) has been reported in 63-73% of children at diagnosis [Haddad et al. (1997); Blood 89: 794-800; Horne et al. (2008); Br J Haematol 140: 327-335]. Patients can present with neurologic symptoms, abnormal CSF cytology, abnormal neuro-imaging, or a combination of these findings. CNS involvement is usually associated with a poor prognosis and increased mortality. The 3 year overall survival is 44% in patients with CNS involvement compared to 67% in patients without CNS involvement at diagnosis [Horne et al. (2008); Br J Haematol 140: 327-335]. We describe a treatment strategy employing systemic dexamethasone to control CNS disease in a patient with familial HLH and persistent CNS disease post Bone Marrow Transplant.

Alternative donor hematopoietic stem cell transplantation for sickle cell disease.

Most patients who could be cured of sickle cell disease (SCD) with stem cell transplantation do not have a matched sibling donor. Successful use of alternative donors, including mismatched family members, could provide a donor for almost all patients with SCD. The use of a reduced-intensity conditioning regimen may decrease late adverse effects. Ten patients with symptomatic SCD underwent CD34+ cell-selected, T-cell-depleted peripheral blood stem cell transplantation from a mismatched family member or unrelated donor. A reduced-intensity conditioning regimen including melphalan, thiotepa, fludarabine, and rabbit anti-thymocyte globulin was used. Patients were screened for a companion study for immune reconstitution that included a donor lymphocyte infusion given 30-42 days after transplant with intravenous methotrexate as graft-versus-host disease (GVHD) prophylaxis. Seven eligible patients were treated on the companion study. Nine of 10 patients are alive with a median follow-up of 49 months (range, 14-60 months). Surviving patients have stable donor hematopoietic engraftment (mean donor chimerism, 99.1% ± 0.7%). There were no sickle cell complications after transplant. Two patients had grade II-IV acute GVHD. One patient had chronic GVHD. Epstein-Barr virus-related posttransplant lymphoproliferative disorder (PTLD) occurred in 3 patients, and 1 patient died as a consequence of treatment of PTLD. Two-year overall survival was 90%, and event-free survival was 80%. A reduced-intensity conditioning regimen followed by CD34+ cell-selected, T-cell-depleted alternative donor peripheral blood stem cell transplantation achieved primary engraftment in all patients with a low incidence of GVHD, although PTLD was problematic. This trial was registered at clinicaltrials.gov as #NCT00968864.