title: Treatment of familial hemophagocytic lymphohistiocytosis with bone marrow transplantation from HLA genetically nonidentical donors.
abstract: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic disorder associated with the onset early in life of overwhelming activation of T lymphocytes and macrophages invariably leading to death. Allogeneic bone marrow transplantation (BMT) from an HLA-identical related donor is the treatment of choice in patients with this disease. However, fewer than 20% of patients have a disease-free HLA-identical sibling. BMT from HLA-nonidentical related donors has previously met with poor results, with graft rejection a major obstacle in all cases. We describe BMTs from HLA-nonidentical related donors (n = 13) and from a matched unrelated donor (n = 1) performed in two centers in 14 consecutive cases of FHL. Remission of disease was achieved before BMT in 10 patients. Marrow was T-cell-depleted to minimize graft-versus-host disease (GVHD). Antiadhesion antibodies specific for the alpha chain of the leukocyte function-associated antigen-1 (LFA-1, CD11a) and the CD2 molecules were infused pre-BMT and post-BMT to help prevent graft rejection, in addition to a conditioning regimen of busulfan (BU), cyclophosphamide (CP), and etoposide (VP16) or antithymocyte globulin (ATG). Sustained engraftment was obtained in 11 of 17 transplants (3 patients had 2 transplants) and disease-free survival in 9 patients with a follow-up period of 8 to 69 months (mean, 33). Acute GVHD greater than stage I was not observed, and 1 patient had mild cutaneous chronic GVHD that resolved. Toxicity due to the BMT procedure was low. Results obtained using this protocol are promising in terms of engraftment and event-free survival within the limitations of the small sample. We conclude that an immunologic approach in terms of drugs used to obtain disease remission and a conditioning regimen that includes antiadhesion molecules in T-cell-depleted BMT from HLA genetically nonidentical donors is an alternative treatment that warrants further study in FHL patients who lack a suitable HLA genetically identical donor.
authors.affiliation: Unité d'Immuno-Hématologie Pédiatrique, Institut National pour la Santé et la Recherche Medicale U429, and Laboratoire d'immunologie, H-opital Necker-Enfants Malades, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Jabado
authors.forename: E R
authors.initials: ER
authors.lastname: de Graeff-Meeder
authors.forename: M
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: E
authors.initials: E
authors.lastname: Haddad
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: M
authors.initials: M
authors.lastname: Benkerrou
authors.forename: R
authors.initials: R
authors.lastname: Dufourcq
authors.forename: S
authors.initials: S
authors.lastname: Caillat
authors.forename: S
authors.initials: S
authors.lastname: Blanche
authors.forename: A
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002678:Chimera; D005260:Female; D015616:Histiocytosis, Non-Langerhans-Cell / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome